A Mathematical Model for DNA Damage and Repair

In cells, DNA repair has to keep up with DNA damage to maintain the integrity of the genome and prevent mutagenesis and carcinogenesis. While the importance of both DNA damage and repair is clear, the impact of imbalances between both processes has not been studied. In this paper, we created a combined mathematical model for the formation of DNA adducts from oxidative estrogen metabolism followed by base excision repair (BER) of these adducts. The model encompasses a set of differential equations representing the sequence of enzymatic reactions in both damage and repair pathways. By combining both pathways, we can simulate the overall process by starting from a given time-dependent concentration of 17β-estradiol (E2) and 2′-deoxyguanosine, determine the extent of adduct formation and the correction by BER required to preserve the integrity of DNA. The model allows us to examine the effect of phenotypic and genotypic factors such as different concentrations of estrogen and variant enzyme haplotypes on the formation and repair of DNA adducts

Bertrand competition with capacity constraints: mergers among parking lots

Abstract To analyze the e ects of mergers among ÿrms facing capacity constraints, we develop a numerical model of price-setting behavior among multi-product ÿrms di erentiated by location and capacity. We perform a number of computational experiments designed to inform merger policy, with speciÿc reference to the Central Parking-Allright merger of 1999. The experiments show that capacity constraints on merging ÿrms attenuate merger e ects by much more than capacity constraints on non-merging ÿrms amplify them. The experiments also highlight the dependence of merger welfare e ects on parking demand. In preparation for further industry consolidation, we propose estimators of parking demand to more precisely estimate the costs and beneÿts of future mergers

Bertrand competition with capacity constraints: mergers among parking lots

Abstract To analyze the e ects of mergers among ÿrms facing capacity constraints, we develop a numerical model of price-setting behavior among multi-product ÿrms di erentiated by location and capacity. We perform a number of computational experiments designed to inform merger policy, with speciÿc reference to the Central Parking-Allright merger of 1999. The experiments show that capacity constraints on merging ÿrms attenuate merger e ects by much more than capacity constraints on non-merging ÿrms amplify them. The experiments also highlight the dependence of merger welfare e ects on parking demand. In preparation for further industry consolidation, we propose estimators of parking demand to more precisely estimate the costs and beneÿts of future mergers

A Computational Model of Quantitative Chromatin Immunoprecipitation (ChIP) Analysis

Chromatin immunoprecipitation (ChIP) analysis is widely used to identify the locations in genomes occupied by transcription factors (TFs). The approach involves chemical cross-linking of DNA with associated proteins, fragmentation of chromatin by sonication or enzymatic digestion, immunoprecipitation of the fragments containing the protein of interest, and then PCR or hybridization analysis to characterize and quantify the genomic sequences enriched. We developed a computational model of quantitative ChIP analysis to elucidate the factors contributing to the method’s resolution. The most important variables identified by the model were, in order of importance, the spacing of the PCR primers, the mean length of the chromatin fragments, and, unexpectedly, the type of fragment width distribution, with very small DNA fragments and smaller amplicons providing the best resolution of TF binding. One of the major predictions of the model was also validated experimentally

Using gene expression data to identify certain gastro-intestinal diseases

BACKGROUND: Inflammatory bowel diseases, ulcerative colitis and Crohn’s disease are considered to be of autoimmune origin, but the etiology of irritable bowel syndrome remains elusive. Furthermore, classifying patients into irritable bowel syndrome and inflammatory bowel diseases can be difficult without invasive testing and holds important treatment implications. Our aim was to assess the ability of gene expression profiling in blood to differentiate among these subject groups. METHODS: Transcript levels of a total of 45 genes in blood were determined by quantitative real-time polymerase chain reaction (RT-PCR). We applied three separate analytic approaches; one utilized a scoring system derived from combinations of ratios of expression levels of two genes and two different support vector machines. RESULTS: All methods discriminated different subject cohorts, irritable bowel syndrome from control, inflammatory bowel disease from control, irritable bowel syndrome from inflammatory bowel disease, and ulcerative colitis from Crohn’s disease, with high degrees of sensitivity and specificity. CONCLUSIONS: These results suggest these approaches may provide clinically useful prediction of the presence of these gastro-intestinal diseases and syndromes

Technology Development for the Advanced Technology Large Aperture Space Telescope (ATLAST) as a Candidate Large UV-Optical-Infrared (LUVOIR) Surveyor

The Advanced Technology Large Aperture Space Telescope (ATLAST) team has identified five key technologies to enable candidate architectures for the future large-aperture ultraviolet/optical/infrared (LUVOIR) space observatory envisioned by the NASA Astrophysics 30-year roadmap, Enduring Quests, Daring Visions. The science goals of ATLAST address a broad range of astrophysical questions from early galaxy and star formation to the processes that contributed to the formation of life on Earth, combining general astrophysics with direct-imaging and spectroscopy of habitable exoplanets. The key technologies are: internal coronagraphs, starshades (or external occulters), ultra-stable large-aperture telescopes, detectors, and mirror coatings. Selected technology performance goals include: 1x1010 raw contrast at an inner working angle of 35 milli-arcseconds, wavefront error stability on the order of 10 pm RMS per wavefront control step, autonomous on-board sensing & control, and zero-read-noise single-photon detectors spanning the exoplanet science bandpass between 400 nm and 1.8 m. Development of these technologies will provide significant advances over current and planned observatories in terms of sensitivity, angular resolution, stability, and high-contrast imaging. The science goals of ATLAST are presented and flowed down to top-level telescope and instrument performance requirements in the context of a reference architecture: a 10-meter-class, segmented aperture telescope operating at room temperature (~290 K) at the sun-Earth Lagrange-2 point. For each technology area, we define best estimates of required capabilities, current state-of-the-art performance, and current Technology Readiness Level (TRL) - thus identifying the current technology gap. We report on current, planned, or recommended efforts to develop each technology to TRL 5