Spatial Evolution of the US Urban System

We test implications of econom c geography models for location,size and growth of cities with US Census data for 1900 - 1990. Our tests involve non-parametr c estimations of stochastic kernels for the distributions of city sizes and growth rates, conditional on various measures of market potential and on features of neighbors. We show that while these relationships change during the twentieth century, by 1990 they stabilize such that the size distribution of cities conditional on a range of spatial variables are all roughly independent of these conditioning variables. In contrast, similar results suggest that there is a spatial element to the city wage distribution. Our parametric estimations for growth rates against market potential, entry of neighbors, and own lagged population imply a negative effect of market potential on growth rates, unless own lagged population is also ncluded, in which case market potential has a positive effect and own lagged population a negative one. Cities grow faster when they are small relative to their market potential. In total, our results support some theoretical predictions, but also provide a number of interesting puzzles.urban growth, spatial evolution, economics geography

Tertiary Alcohols as Radical Precursors for the Introduction of Tertiary Substituents into Heteroarenes

Despite many recent advances in the radical alkylation of electron-deficient heteroarenes since the seminal reports by Minisci and co-workers, methods for the direct incorporation of tertiary alkyl substituents into nitrogen heteroarenes are limited. This report describes the use of tert-alkyl oxalate salts, derived from tertiary alcohols, to introduce tertiary substituents into a variety of heterocyclic substrates. This reaction has reasonably broad scope, proceeds rapidly under mild conditions, and is initiated by either photochemical or thermal activation. Insights into the underlying mechanism of the higher yielding visible-light initiated process were obtained by flash photolysis studies, whereas computational studies provided insight into the reaction scope

Attenuation of hedgehog/GLI signaling by NT1721 extends survival in pancreatic cancer.

BackgroundPancreatic cancer is one of the most lethal malignancies due to frequent late diagnosis, aggressive tumor growth and metastasis formation. Continuously raising incidence rates of pancreatic cancer and a lack of significant improvement in survival rates over the past 30 years highlight the need for new therapeutic agents. Thus, new therapeutic agents and strategies are urgently needed to improve the outcome for patients with pancreatic cancer. Here, we evaluated the anti-tumor activity of a new natural product-based epidithiodiketopiperazine, NT1721, against pancreatic cancer.MethodsWe characterized the anticancer efficacy of NT1721 in multiple pancreatic cancer cell lines in vitro and in two orthotopic models. We also compared the effects of NT1721 to clinically used hedgehog inhibitors and the standard-of-care drug, gemcitabine. The effect of NT1721 on hedgehog/GLI signaling was assessed by determining the expression of GLI and GLI target genes both in vitro and in vivo.ResultsNT1721 displayed IC50 values in the submicromolar range in multiple pancreatic cancer cell lines, while largely sparing normal pancreatic epithelial cells. NT1721 attenuated hedgehog/GLI signaling through downregulation of GLI1/2 transcription factors and their downstream target genes, which reduced cell proliferation and invasion in vitro and significantly decreased tumor growth and liver metastasis in two preclinical orthotopic mouse models of pancreatic cancer. Importantly, treatment with NT1721 significantly improved survival times of mice with pancreatic cancer compared to the standard-of-care drug, gemcitabine.ConclusionsFavorable therapeutics properties, i.e. 10-fold lower IC50 values than clinically used hedgehog inhibitors (vismodegib, erismodegib), a 90% reduction in liver metastasis and significantly better survival times compared to the standard-of-care drug, gemcitabine, provide a rational for testing NT1721 in the clinic either as a single agent or possibly in combination with gemcitabine or other therapeutic agents in PDAC patients overexpressing GLI1/2. This could potentially result in promising new treatment options for patients suffering from this devastating disease

Gigaflop performance on a CRAY-2: Multitasking a computational fluid dynamics application

The methodology is described for converting a large, long-running applications code that executed on a single processor of a CRAY-2 supercomputer to a version that executed efficiently on multiple processors. Although the conversion of every application is different, a discussion of the types of modification used to achieve gigaflop performance is included to assist others in the parallelization of applications for CRAY computers, especially those that were developed for other computers. An existing application, from the discipline of computational fluid dynamics, that had utilized over 2000 hrs of CPU time on CRAY-2 during the previous year was chosen as a test case to study the effectiveness of multitasking on a CRAY-2. The nature of dominant calculations within the application indicated that a sustained computational rate of 1 billion floating-point operations per second, or 1 gigaflop, might be achieved. The code was first analyzed and modified for optimal performance on a single processor in a batch environment. After optimal performance on a single CPU was achieved, the code was modified to use multiple processors in a dedicated environment. The results of these two efforts were merged into a single code that had a sustained computational rate of over 1 gigaflop on a CRAY-2. Timings and analysis of performance are given for both single- and multiple-processor runs

Accumulation of Biomass and Mineral Elements with Calendar Time by Corn: Application of the Expanded Growth Model

The expanded growth model is developed to describe accumulation of plant biomass (Mg ha−1) and mineral elements (kg ha−1) in with calendar time (wk). Accumulation of plant biomass with calendar time occurs as a result of photosynthesis for green land-based plants. A corresponding accumulation of mineral elements such as nitrogen, phosphorus, and potassium occurs from the soil through plant roots. In this analysis, the expanded growth model is tested against high quality, published data on corn (Zea mays L.) growth. Data from a field study in South Carolina was used to evaluate the application of the model, where the planting time of April 2 in the field study maximized the capture of solar energy for biomass production. The growth model predicts a simple linear relationship between biomass yield and the growth quantifier, which is confirmed with the data. The growth quantifier incorporates the unit processes of distribution of solar energy which drives biomass accumulation by photosynthesis, partitioning of biomass between light-gathering and structural components of the plants, and an aging function. A hyperbolic relationship between plant nutrient uptake and biomass yield is assumed, and is confirmed for the mineral elements nitrogen (N), phosphorus (P), and potassium (K). It is concluded that the rate limiting process in the system is biomass accumulation by photosynthesis and that nutrient accumulation occurs in virtual equilibrium with biomass accumulation