bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Epidermal Growth Factor Receptor Mutations in Serum as a Predictor of the Response to Gefitinib in Patients with Non–Small-Cell Lung Cancer
Authors: Kimura Hideharu , Kasahara Kazuo , Kawaishi Makoto , Kunitoh Hideo , Tamura Tomohide , Holloway Brian , Nishio Kazuto 
Published: July 2006

Abstract
Cases of non–small-cell lung cancer (NSCLC) carrying the somatic mutation of epidermal growth factor receptor (EGFR) have been shown to be hyperresponsive to the EGFR tyrosine kinase inhibitor gefitinib (IRESSA). If EGFR mutations can be observed in serum DNA, this could serve as a noninvasive source of information on the genotype of the original tumor cells that could influence treatment and the ability to predict patient response to gefitinib. Serum genomic DNA was obtained from Japanese patients with NSCLC before first-line gefitinib monotherapy. Scorpion Amplified Refractory Mutation System technology was used to detect EGFR mutations. Wild-type EGFR was detected in all of the 27 serum samples. EGFR mutations were detected in 13 of 27 (48.1%) patients and two major EGFR mutations were identified (E746_A750del and L858R). The EGFR mutations were seen significantly more frequently in patients with a partial response than in patients with stable disease or progressive disease (P = 0.046, Fisher's exact test). The median progression-free survival was significantly longer in patients with EGFR mutations than in patients without EGFR mutations (200 versus 46 days; P = 0.005, log-rank test). The median survival was 611 days in patients with EGFR mutations and 232 days in patients without EGFR mutations (P &gt; 0.05). In pairs of tumor and serum samples obtained from 11 patients, the EGFR mutation status in the tumors was consistent with those in the serum of 8 of 11 (72.7%) of the paired samples. Thus, EGFR mutations were detectable using Scorpion Amplified Refractory Mutation System technology in serum DNA from patients with NSCLC. These results suggest that patients with EGFR mutations seem to have better outcomes with gefitinib treatment, in terms of progression-free survival, overall survival, and response, than those patients without EGFR mutations.
Ex vivo and In vivo Delivery of Anti-Tissue Factor Short Interfering RNA Inhibits Mouse Pulmonary Metastasis of B16 Melanoma Cells
Authors: Amarzguioui Mohammed , Peng Qian , Wiiger Merete T. , Vasovic Vlada , Babaie Eshrat , Holen Torgeir , Nesland Jahn M. , Prydz Hans 
Published: July 2006

Abstract
Purpose: The coagulation trigger tissue factor has been implicated in tumor growth, angiogenesis, and metastasis. In this study, we explore the effects of ex vivo and in vivo delivery of short interfering RNA (siRNA) targeting tissue factor on B16 melanoma colonization of the lung in a murine model for metastasis. The purposes of this work are to establish a noncytotoxic in vivo model for investigation of tissue factor function and provide preclinical assessment of the therapeutic potential of tissue factor siRNA for prevention of metastasis.
Experimental Design and Results: C57BL/6 mice were evaluated for pulmonary metastases following tail vein injection of B16 cells transfected with either active or inactive siRNA. Mice receiving cells transfected with active siRNA had significantly lower numbers of pulmonary tumors compared with mice injected with control cells (transfected with inactive siRNA). The average time point at which the mice started to exhibit tumor-associated stress was also increased significantly from 22 days for the control group to 27 days for the experimental group (P = 0.01). In a therapeutically more relevant model, where the siRNA was delivered i.p. and the cells (untransfected) by tail vein injection, an inhibitory effect on metastasis was observed when the siRNA treatment was initiated either before or at the time of cell injection.
Conclusions: The results suggest that tissue factor has a crucial function in promoting lung tumor metastasis of blood-borne tumor cells in the early stages of the tumor take process and further suggest that treatment with tissue factor siRNA may become a viable clinical strategy for prevention of tumor metastasis.
Preclinical pharmacokinetics and metabolism of a novel diaryl pyrazole resorcinol series of heat shock protein 90 inhibitors
Authors: Smith Nicola F. , Hayes Angela , James Karen , Nutley Bernard P. , McDonald Edward , Henley Alan , Dymock Brian , Drysdale Martin J. , Raynaud Florence I. , Workman Paul 
Published: July 2006

Abstract
CCT018159 was recently identified as a novel inhibitor of heat shock protein (Hsp) 90, a promising target for cancer therapy. Pharmacokinetic and metabolic properties are likely to be important for efficacy and need to be optimized during drug development. Here, we define the preclinical metabolism and pharmacokinetics of CCT018159 and some early derivatives. In addition, we assess in vitro metabolic stability screening and in vivo cassette dosing (simultaneous administration of several compounds to a single animal) as approaches to investigate these compounds. The plasma clearance following individual i.v. administration to mice was rapid (0.128–0.816 L/h), exceeding hepatic blood flow. For CCT066950 and CCT066952, this could be attributed in part to extensive (&gt;80%) blood cell binding. Oral bioavailability ranged from 1.8% to 29.6%. Tissue distribution of CCT066952 was rapid and moderate, and renal excretion of the compounds was minimal (&lt;1% of dose excreted). Compounds underwent rapid glucuronidation both in vivo and following incubation with mouse liver microsomes. However, whereas CCT066965 was metabolized to the greatest extent in vitro, this compound displayed the slowest plasma clearance. The rank order of the compounds from the highest to lowest area under the curve was the same following discrete and cassette dosing. Furthermore, pharmacokinetic variables were similar whether the compounds were dosed alone or in combination. We conclude that the pharmacokinetics of CCT018159 are complex. Cassette dosing is currently the best option available to assess the pharmacokinetics of this promising series of compounds in relatively high throughput and is now being applied to identify compounds with optimal pharmacokinetic properties during structural analogue synthesis. [Mol Cancer Ther 2006;5(6):1628–37]
Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-κB (NF-κB) activation and NF-κB–regulated gene expression
Authors: Ichikawa Haruyo , Takada Yasunari , Shishodia Shishir , Jayaprakasam Bolleddula , Nair Muraleedharan G. , Aggarwal Bharat B. 
Published: July 2006

AbstractThe plant Withania somnifera Dunal (Ashwagandha), also known as Indian ginseng, is widely used in the Ayurvedic system of medicine to treat tumors, inflammation, arthritis, asthma, and hypertension. Chemical investigation of the roots and leaves of this plant has yielded bioactive withanolides. Earlier studies showed that withanolides inhibit cyclooxygenase enzymes, lipid peroxidation, and proliferation of tumor cells. Because several genes that regulate cellular proliferation, carcinogenesis, metastasis, and inflammation are regulated by activation of nuclear factor-κB (NF-κB), we hypothesized that the activity of withanolides is mediated through modulation of NF-κB activation. For this report, we investigated the effect of the withanolide on NF-κB and NF-κB-regulated gene expression activated by various carcinogens. We found that withanolides suppressed NF-κB activation induced by a variety of inflammatory and carcinogenic agents, including tumor necrosis factor (TNF), interleukin-1β, doxorubicin, and cigarette smoke condensate. Suppression was not cell type specific, as both inducible and constitutive NF-κB activation was blocked by withanolides. The suppression occurred through the inhibition of inhibitory subunit of IκBα kinase activation, IκBα phosphorylation, IκBα degradation, p65 phosphorylation, and subsequent p65 nuclear translocation. NF-κB-dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR-associated death domain, TNFR-associated factor 2, and IκBα kinase was also suppressed. Consequently, withanolide suppressed the expression of TNF-induced NF-κB-regulated antiapoptotic (inhibitor of apoptosis protein 1, Bfl-1/A1, and FADD-like interleukin-1β-converting enzyme–inhibitory protein) and metastatic (cyclooxygenase-2 and intercellular adhesion molecule-1) gene products, enhanced the apoptosis induced by TNF and chemotherapeutic agents, and suppressed cellular TNF-induced invasion and receptor activator of NF-κB ligand-induced osteoclastogenesis. Overall, our results indicate that withanolides inhibit activation of NF-κB and NF-κB-regulated gene expression, which may explain the ability of withanolides to enhance apoptosis and inhibit invasion and osteoclastogenesis. [Mol Cancer Ther 2006;5(6):1434–45]
Climate and Climate Change over North America as Simulated by the Canadian RCM
Authors: Plummer D. A. , Caya D. , Frigon A. , Côté H. , Giguère M. , Paquin D. , Biner S. , Harvey R. , de Elia R. 
Published: July 2006

Abstract
An analysis of several multidecadal simulations of the present (1971–90) and future (2041–60) climate from the Canadian Regional Climate Model (CRCM) is presented. The effects on the CRCM climate of model domain size, internal variability of the general circulation model (GCM) used to provide boundary conditions, and modifications to the physical parameterizations used in the CRCM are investigated. The influence of boundary conditions is further investigated by comparing the GCM-driven simulations of the current climate with simulations performed using boundary conditions from meteorological reanalyses. The present climate of the model in these different configurations is assessed by comparing the seasonal averages and interannual variability of precipitation and surface air temperature with an observed climatology. Generally, small differences are found between the two simulations on different domains, though both domains are quite large as compared with previously reported results. Simulations driven by GCM output show a significant warm bias for wintertime surface air temperatures over northern regions. This warm bias is much reduced in the GCM-driven simulation when an updated set of physical parameterizations is used in the CRCM. The warm bias is also reduced for simulations with the standard set of physical parameterizations when the CRCM is driven with reanalysis data. However, use of the modified physics package for reanalysis-driven simulations results in surface air temperatures that are colder than the observations. Summertime precipitation in the model is much larger than observed, a bias that is present in both the GCM-driven and reanalysis-driven simulations. The bias in summertime precipitation is reduced for both types of driving data when the updated set of physical parameterizations is used. Model projections of climate change between the present and future periods are also presented and the sensitivity of these projections to many of the above-mentioned modifications is assessed. Changes in surface air temperature are predicted to be largest over northern regions in winter, with smaller changes over more southerly regions and in the summer season. Changes in seasonal average precipitation are projected to be in the range of ±10% of present-day amounts for most regions and seasons. The CRCM projections of surface air temperature changes are strongly affected by the internal variability of the driving GCM over high northern latitudes and to changes in the physical parameterizations over many regions for the summer season.
Climatology Models for Extreme Hurricane Winds near the United States
Authors: Jagger Thomas H. , Elsner James B. 
Published: July 2006

AbstractThe rarity of severe coastal hurricanes implies that empirical estimates of extreme wind speed return levels will be unreliable. Here climatology models derived from extreme value theory are estimated using data from the best-track [Hurricane Database (HURDAT)] record. The occurrence of a hurricane above a specified threshold intensity level is assumed to follow a Poisson distribution, and the distribution of the maximum wind is assumed to follow a generalized Pareto distribution. The likelihood function is the product of the generalized Pareto probabilities for each wind speed estimate. A geographic region encompassing the entire U.S. coast vulnerable to Atlantic hurricanes is of primary interest, but the Gulf Coast, Florida, and the East Coast regions are also considered. Model parameters are first estimated using a maximum likelihood (ML) procedure. Results estimate the 100-yr return level for the entire coast at 157 kt (±10 kt), but at 117 kt (±4 kt) for the East Coast region (1 kt = 0.514 m s−1). Highest wind speed return levels are noted along the Gulf Coast from Texas to Alabama. The study also examines how the extreme wind return levels change depending on climate conditions including El Niño–Southern Oscillation, the Atlantic Multidecadal Oscillation, the North Atlantic Oscillation, and global temperature. The mean 5-yr return level during La Niña (El Niño) conditions is 125 (116) kt, but is 140 (164) kt for the 100-yr return level. This indicates that La Niña years are the most active for the occurrence of strong hurricanes, but that extreme hurricanes are more likely during El Niño years. Although El Niño inhibits hurricane formation in part through wind shear, the accompanying cooler lower stratosphere appears to increase the potential intensity of hurricanes that do form. To take advantage of older, less reliable data, the models are reformulated using Bayesian methods. Gibbs sampling is used to integrate the prior over the likelihood to obtain the posterior distributions for the model parameters conditional on global temperature. Higher temperatures are conditionally associated with more strong hurricanes and higher return levels for the strongest hurricane winds. Results compare favorably with an ML approach as well as with recent modeling and observational studies. The maximum possible near-coastal wind speed is estimated to be 208 kt (183 kt) using the Bayesian (ML) approach.
Anomalous Distortion and Stacking Column Formation of [Ni(dmit)2]− Induced by Propeller-Shaped Dye Cations, Crystal Violet and Basic Fuchsin
Authors: Soneta Yuji , Midorikawa Tomoko , Miyamura Kazuo 
Published: July 2006

Abstract
(CV+)[Ni(dmit)2]·1/2(C6H6) (1) and (BF+)[Ni(dmit)2] (2) (dmit = 2-thioxo-1,3-dithiole-4,5-dithiolato, CV+ = cation of Crystal Violet, BF+ = cation of Basic Fuchsin) were prepared and characterized by X-ray crystal structural analysis. In the crystal structure of 1, the Ni(dmit)2 unit was bent at Ni in a V shape with an angle of 13.7° and tetrahedral distortion of 8.8° around Ni was also present that originated from the steric effect of the propeller-shaped CV cation. In the case of 2, BF and [Ni(dmit)2]− formed an independent stacking column in which [Ni(dmit)2]− were stacked alternately rotated with an angle of 90° to each other. 1 and 2 exhibited semiconducting behavior with room-temperature conductivities of 2.9 × 10−7 and 9.0 × 10−5 S cm−1, respectively.
Rice Policy in Japan's Economic Development
Authors: Hayami Yujiro 
Published: July 2006

AbstractUntil only a decade ago, Japan's rice policy had been primarily designed to procure “cheap” rice for the industrial population from domestic and colonial producers. For the promotion of industrialization and economic growth the price of rice, the principal wage good, had been kept low to prevent the rise in the wage rate of urban industrial workers. The shift from the traditional cheap rice policy to a recent policy of high price supports is due to the decline in the role of rice as a wage good. The rapid rise in per capita income and the dramatic transformation of Japan's industrial structure contributed to the policy change.
Agricultural Trade Intensity: The European Markets and the U. S.
Authors: Carney M. K. 
Published: July 2006

AbstractTo examine developments in agricultural trade between countries in EEC and EFTA, the U. S., and an aggregate of other countries, a measure of trading intensity is calculated for years from 1960 through 1969. Intra‐EFTA trade intensified; EEC trade did not. U. S. trade with the remainder of the world intensified.
The Farm‐Retail Price Spread in a Competitive Food Industry
Authors: Gardner Bruce L. 
Published: July 2006

AbstractConsistency with market equilibrium places constraints on the pricing policies of food marketing firms in a competitive industry. This paper examines the implications of simultaneous equilibrium in three related markets: retail food, farm output, and marketing services. From equations representing the demand and supply sides of each market, elasticities are generated which show how the farm‐retail price spread changes when retail food demand, farm product supply, or the supply function of marketing services shifts. Implications for the viability of simple markup pricing rules and the determinants of the farmer's share of the food dollar are discussed.
A Macro‐Economic Model for Agricultural Sector Analysis
Authors: Byerlee Derek , Halter A. N. 
Published: July 2006

AbstractAgricultural sector analyses for purposes of agricultural policy evaluation and planning in developing countries are generally conducted in a partial equilibrium framework without regard to agricultural‐nonagricultural interactions. A relatively simple simulation model built on an input‐output framework is developed which, in combination with an agricultural sector analysis, enables interactions in the product markets and labor market to be considered. The model is illustrated through linkage with an agricultural simulation model to evaluate alternative agricultural policies in Nigeria. The model also has potential for use with other formal and informal sector analysis techniques.
Comparative Advantage among African Coffee Producers
Authors: Pearson Scott R. , Meyer Ronald K. 
Published: July 2006

AbstractRelative comparative advantage is measured by contrasting country ratios of the domestic resource costs per unit of foreign exchange earned by exporting coffee to the exchange rate. Uganda, Ethiopia, and Tanzania have strong relative comparative advantages in coffee vis‐à‐vis the Ivory Coast, largely because of higher opportunity costs of Ivoirian factors.
Peasants' Response to Modernization Projects in Minifundia Economies
Authors: Benito Carlos A. 
Published: July 2006

AbstractDifferent factors are mentioned in explaining peasants' adoption of modern technologies. A model of the peasant household is developed integrating most of these factors, condensed into a stochastic linear programming framework, and applied to the Puebla area in Mexico. Observed low adoption rates and peasants' participation in modernization projects are explained by opportunity costs of time and uncertainty. The view that labor‐using technologies per se will rapidly increase agricultural production is challenged. The generation of less risky technologies and more emphasis on organizational‐communication aspects are also necessary. Further rural development will require intermediate technologies and organizations.
Pests as a Common Property Resource: A Case Study of Alfalfa Weevil Control
Authors: Regev Uri , Gutierrez Andrew P. , Feder Gershon 
Published: July 2006

AbstractThe biological interactions of a pest‐plant system are incorporated into an optimal pest‐control model, using data and estimated parameters specific to the alfalfa weevil. Due to the externalities inherent in situations involving common property resources, different solutions are obtained for private and societal formulations of the optimization problem. In contrast to current pesticide‐spraying practices, it is shown that pesticide should be applied early in the season, before any damage can be observed.
An Analysis of Alternative Financing Strategies and Equity Retirement Plans for Farm Supply Cooperatives
Authors: Dahl Wilmer A. , Dobson W. D. 
Published: July 2006

AbstractCooperatives are experiencing pressures to increase cash patronage refunds, reduce financing costs, and retire equity capital of farmer‐members who die, retire, or leave the cooperative's service area. Farm supply cooperatives could increase cash patronage refunds by over 90% and reduce financing costs by 6% to 9% by employing moderately different capital acquisition practices. Solvency of the cooperatives could be reduced substantially if mandatory equity retirement plans being considered by legislators and courts were adopted.
On the Incongruity of Program Objectives and Project Evaluation: An Example from the Reclamation Program
Authors: Bromley Daniel W. , Beattie Bruce R. 
Published: July 2006

AbstractIn public programs project evaluation is often based on an objective that is more specific than the general objectives of the program. In such situations, benefits may be underestimated. The magnitude of this underestimation is assessed for a proposed reclamation project in Southern Idaho.
Multi‐Frequency Cobweb Model: Decomposition of the Hog Cycle
Authors: Talpaz Hovav 
Published: July 2006

AbstractThe Cobweb Theorem and the harmonic motion models are extended and integrated to form a multi‐frequency cobweb model explaining the U. S. hog production cycle. The cycle is estimated by a finite, time‐based Fourier Series allowing amplitude and frequency analysis. Six different cycles are discovered operating simultaneously in the attempt to reach a market equilibrium. An independent distributed lag model is estimated, verifying the fundamental hypothesis of the model. The implication is that improved industry performance can be efficiently achieved by control policies to dampen the harmful long period cycles, leaving the short ones unaffected.
Markup Pricing in a Dynamic Model of the Food Industry
Authors: Heien Dale M. 
Published: July 2006

AbstractThis paper presents a dynamic model of farm and retail prices and quantities. Central to the model is the notion that increases in wholesale prices are transmitted to the retail level via markup‐type pricing behavior. This behavior is shown to be consistent with firm optimization under the assumption of constant returns to scale and Leontief production technology at the retail level. The markup hypothesis is tested using the Granger‐Sims causality tests. Markup‐type price relationships are then estimated for twenty‐two food commodities.
Agricultural Development and Land Tenancy in a Peasant Economy: A Theoretical and Empirical Analysis
Authors: Bardhan Pranab K. 
Published: July 2006

AbstractIn this paper we have a two‐season model of agricultural production in a peasant economy, with labor unemployment in the lean season, land rationing at a conventionally fixed crop share by a monopolistic landlord who is also the financier of consumption credit for the sharecropper families. We then work out hypotheses about the relation of the equilibrium percentage of area under tenancy with land quality factors, labor‐intensity of crops, extent of unemployment, interest rates, weather uncertainty, etc. Most of the hypotheses are confirmed by interstate cross‐section evidence from India in early 1950s.
The Effects of Property Taxes and Local Public Services upon Residential Property Values in Small Wisconsin Cities
Authors: McMillan Melville , Carlson Richard 
Published: July 2006

AbstractContrary to the results of similar studies in metropolitan areas, this investigation found no evidence that local property taxes and public expenditures were capitalized into the value of owner‐occupied homes in small cities despite their considerable dependence upon the property tax. This does not imply that residents of small cities are insensitive to fiscal differences but rather is evidence of the more elastic supply of land for housing in nonmetropolitan communities.