Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas

Platinum drug-resistance in ovarian cancers is a major factor contributing to chemotherapeutic resistance of recurrent disease. Members of the Bcl-2 family such as the anti-apoptotic protein Bcl-XL have been shown to play a role in this resistance. Consequently, concurrent inhibition of Bcl-XL in combination with standard chemotherapy may improve treatment outcomes for ovarian cancer patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-XL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo\ud experimental data, wherein tumor xenografts were established in mice and treated with ABT-737 and carboplatin on a fixed periodic schedule, alone or in combination, and tumor sizes recorded regularly. We show that the validated model can be used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the time of infusion of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin administered each week combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. We also investigate the potential of ABT-737 co-therapy with carboplatin to prevent or delay the onset of carboplatin-resistance under two scenarios. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, the model is used to identify drug delivery schedules that induce tumor remission with even low doses of combination therapy. When resistance is intrinsic, due to a pre-existing cohort of resistant cells, tumor remission is no longer feasible, but our model can be used to identify dosing strategies that extend disease-free survival periods. These results underscore the potential of our model to accelerate the development of novel therapeutics such as ABT-737, by predicting optimal treatment strategies when these drugs are given in combination with currently approved cancer medications

Vegetation density as deduced from ERTS-1 MSS response

Reflectance from vegetation increases with increasing vegetation density in the 0.75- to 1.35 micron wavelength interval. Therefore, ERTS-1 bands 6 (0.7 to 0.8 micron) and 7 (0.8 to 1.1 micron) contain information that should relate to the probable yield of crops and the animal carrying capacity of rangeland. The results of an experiment designed specifically to test the relations among leaf area index (LAI), plant population, plant cover and plant height, and the ERTS-1 MSS responses for 3 corn, 10 sorghum, and 10 cotton fields are given. Plant population was as useful as LAI for characterizing the sorghum and corn fields, and plant height was as good as LAI for characterizing cotton fields. These findings generally support the utility of ERTS-1 data for explaining variability in green biomass, harvestable forage and other indicators of productivity

Comparison of LANDSAT-2 and field spectrometer reflectance signatures of south Texas rangeland plant communities

The accuracy was assessed for an atmospheric correction method that depends on clear water bodies to infer solar and atmospheric parameters for radiative transfer equations by measuring the reflectance signature of four prominent south Texas rangeland plants with the LANDSAT satellite multispectral scanner (MSS) and a ground based spectroradiometer. The rangeland plant reflectances produced by the two sensors were correlated with no significant deviation of the slope from unity or of the intercept from zero. These results indicated that the atmospheric correction produced LANDSAT MSS estimates of rangeland plant reflectances that are as accurate as the ground based spectroradiometer

Soil, water, and vegetation conditions in south Texas

The author has identified the following significant results. Software development for a computer-aided crop and soil survey system is nearing completion. Computer-aided variety classification accuracies using LANDSAT-1 MSS data for a 600 hectare citrus farm were 83% for Redblush grapefruit and 91% for oranges. These accuracies indicate that there is good potential for computer-aided inventories of grapefruit and orange citrus orchards with LANDSAT-type MSS data. Mean digital values of clouds differed statistically from those for crop, soil, and water entities, and those for cloud shadows were enough lower than sunlit crop and soil to be distinguishable. The standard errors of estimate for the calibration of computer compatible tape coordinate system (pixel and record) to earth coordinate system (longitude and latitude) for 6 LANDSAT scenes ranged from 0.72 to 1.50 pixels and from 0.58 to 1.75 records

Estimating total standing herbaceous biomass production with LANDSAT MSS digital data

Rangeland biomass data were correlated with spectral vegetation indices, derived from LANDSAT MSS data. LANDSAT data from five range and three other land use sites in Willacv and Cameron Counties were collected on October 17 and December 10, 1975, and on July 31 and September 23, 1976. The overall linear correlation of total standing herbaceous biomass with the LANDSAT derived perpendicular vegetation index was highly significant (r = 0.90**) for these four dates. The standard error of estimate was 722 kg/ha. Biomass data were recorded for two of these range sites for 8 months (March through October) during the 1976 growing season. Standing green biomass accounted for most of the increase in herbage, starting in June and ending about September and October. These results indicate that satellite data may be useful for the estimation of total standing herbaceous biomass production that could aid range managers in assessing range condition and animal carrying capacities of large and inaccessible range holdings

Reflectance of vegetation, soil, and water

The author has identified the following significant results. Iron deficient and normal grain sorghum plants were sufficiently different spectrally in ERTS-1 band 5 CCT data to detect chlorotic sorghum areas 2.8 acres (1.1 hectares) or larger in size in computer printouts of the MSS data. The ratio of band 5 to band 7 or band 7 minus band 5 relates to vegetation ground cover conditions and helps to select training samples representative of differing vegetation maturity or vigor classes and to estimate ground cover or green vegetation density in the absence of ground information. The four plant parameters; leaf area index, plant population, plant cover, and plant height explained 87 to 93% of the variability in band 6 digital counts and from 59 to 90% of the variation in bands 4 and 5. A ground area 2244 acres in size was classified on a pixel by pixel basis using simultaneously acquired aircraft support and ERTS-1 data. Overall recognition for vegetables, immature crops and mixed shrubs, and bare soil categories was 64.5% for aircraft and 59.6% for spacecraft data, respectively. Overall recognition results on a per field basis were 61.8% for aircraft and 62.8% for ERTS-1 data

Determining DfT Hardware by VHDL-AMS Fault Simulation for Biological Micro-Electronic Fluidic Arrays

The interest of microelectronic fluidic arrays for biomedical applications, like DNA determination, is rapidly increasing. In order to evaluate these systems in terms of required Design-for-Test structures, fault simulations in both fluidic and electronic domains are necessary. VHDL-AMS can be used successfully in this case. This paper shows a highly testable architecture of a DNA Bio-Sensing array, its basic sensing concept, fluidic modeling and sensitivity analysis. The overall VHDL-AMS fault simulation of the system is shown

Significance of low energy impact damage on modal parameters of composite beams by design of experiments

This paper presents an experimental study on the effects of multi-site damage on the vibration response of composite beams damaged by low energy impacts around the barely visible impact damage limit (BVID). The variation of the modal parameters with different levels of impact energy and density of damage is studied. Vibration tests have been carried out with both burst random and classical sine dwell excitations in order to compare that which of the methods among Polymax and Half Bandwidth Method is more suitable for damping estimation in the presence of damage. Design of experiments (DOE) performed on the experimental data show that natural frequency is a more sensitive parameter for damage detection than the damping ratio. It also highlighted energy of impact as the factor having a more significant effect on the modal parameters. Half Bandwidth Method is found to be unsuitable for damping estimation in the presence of damage

Optical parameters of leaves of seven weed species

The absorption coefficient (k), infinite reflectance (R), and scattering coefficient (s) were tabulated for five wavelengths and analyzed for statistical differences for seven weed species. The wavelengths were: 0.55-micrometer, 0.65-micrometers, 0.85-micrometer, 1.65-micrometers, and 2.20-micrometer. The R of common lambsquarters (Chenopodium album L.), Johnsongrass (Sorghum halepense (L.) Pers.), and annual sowthistle (Sonchus oleraceus L.) leaves at the 0.85-micrometer wavelength were significantly (p=0.05) higher than for sunflower (Heliantus annus L.), ragweed parthenium (Parthenium hysterophorus L.), or London rocket (Sisymbrium irio L.). Annual sowthistle had the largest k value, and Plamer amaranth (Amaranthus palmer S. Wats.) had the smallest k value at the 0.65 approximately chlorophyll absorption wavelength. In general, john-songress, ragweed parthenium, or London rocket had the largest s values among the five wavelengths, wereas annual sowthistle and plamar amaranth were usually lowest