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Dr. R. Goodwill F. D. Enfield 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1971,41(1):5-12
Summary Two-way selection for 21-day pupa weight was conducted in two highly inbred lines of Tribolium castaneum. The results, after 17 generations of selection, indicated that one of these lines (CSI-10) possessed a moderate amount of genetic variation for the trait selected (21-day pupa weight).When the selected populations were allowed to mate at random for 13 generations, the mean pupa weight regressed to values close to the means in the populations prior to selection. Reciprocal crosses between the high and low select lines revealed that 80% of the variation was associated with the sex chromosomes.The possibility that recurrent mutation was responsible for the genetic variation is discussed. It is concluded that natural selection favoring the heterozygous condition, rather than recurrent mutation, is responsible for the genetic variation. It is suggested that selection occurring between the sublines has reduced the rate at which the inbred line, CSI-10, is approaching complete homozygosity.The data have been taken from the doctoral thesis presented to the faculty of the University of Minnesota, St. Paul, by the senior author.Supported by NSFgrants G-1238, GB-5987 and NIH GM-16074. 相似文献
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Correlated response in male and female sterility to selection for pupa weight in Tribolium castaneum
D. D. Kress F. D. Enfield O. Braskerud 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1971,41(5):197-202
Summary The correlated responses in male and female sterility to 50 generations of individual selection for pupa weight in Tribolium were analyzed. Two replicate lines (S-lines) were selected for heavier pupa weight and stabilizing selection for pupa weight was practiced in two replicate control lines (C-lines). There was close agreement between replicates in both sets of lines for direct and correlated responses. The rate of inbreeding has been constant for all lines (approximately 0.5% per generation).Regression of generation means for pupa weight on generation of selection indicated a significant linear regression in the direct response for both lines. The linear increases of 46 and 55 g. per generation in the S-lines accounted for 98% of the variation among generations and the linear decreases of 5 and 10 g. per generation in the C-lines accounted for 70–90% of the variation in the generation means.Maximum likelihood estimators were used to calculate the frequency of male and female sterility for each generation and line. Average sterility in the base population ranged from about 4 to 12% for both sexes. Polynomial regressions of percent sterility on generation of selection showed that quadratic and higher order regressions were occasionally significant but accounted for a relatively small fraction of the total variation. In the two S-line replicates, linear regression coefficients of percent sterility on generation number were 0.16±.09 and 0.20±.07 for males and 0.72±.08 and 0.54±.08 for females, suggesting a larger correlated response in female than in male sterility. In the C-lines, linear regression coefficients were 0.02±.08 and –.12±.05 for males in the two replicates and –.05±.05 and –.05±.05 for females. Estimates of realized genetic correlations between pupa weight and sterility in the S-lines ranged from 0.04 to 0.14 for males and from 0.14 to 0.37 for females when the heritability of sterility was allowed to take on values from 0.05 to 0.25.Supported by NSF Grants G-1238 and GB-5987, NIH Grant GM-16074 and NIH Fellowship 1 FO2 GM4 5130-01. 相似文献
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David Saleh Gang Wang Benedict Müller Federico Rischawy Simon Kluters Joey Studts Jürgen Hubbuch 《Biotechnology progress》2020,36(4):e2984
Mechanistic modeling of chromatography processes is one of the most promising techniques for the digitalization of biopharmaceutical process development. Possible applications of chromatography models range from in silico process optimization in early phase development to in silico root cause investigation during manufacturing. Nonetheless, the cumbersome and complex model calibration still decelerates the implementation of mechanistic modeling in industry. Therefore, the industry demands model calibration strategies that ensure adequate model certainty in a limited amount of time. This study introduces a directed and straightforward approach for the calibration of pH-dependent, multicomponent steric mass action (SMA) isotherm models for industrial applications. In the case investigated, the method was applied to a monoclonal antibody (mAb) polishing step including four protein species. The developed strategy combined well-established theories of preparative chromatography (e.g. Yamamoto method) and allowed a systematic reduction of unknown model parameters to 7 from initially 32. Model uncertainty was reduced by designing two representative calibration experiments for the inverse estimation of remaining model parameters. Dedicated experiments with aggregate-enriched load material led to a significant reduction of model uncertainty for the estimates of this low-concentrated product-related impurity. The model was validated beyond the operating ranges of the final unit operation, enabling its application to late-stage downstream process development. With the proposed model calibration strategy, a systematic experimental design is provided, calibration effort is strongly reduced, and local minima are avoided. 相似文献
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β-Glucan process-related impurities can be introduced into biopharmaceutical products via upstream or downstream processing or via excipients. This study obtained a comprehensive process-mapping dataset for five monoclonal antibodies to assess β-glucan introduction and clearance during development and production runs at various scales. Overall, 198 data points were available for analysis. The greatest β-glucan concentrations were found in the depth-filtration filtrate (37–2,745 pg/ml). Load volume correlated with β-glucan concentration in the filtrate, whereas flush volume was of secondary importance. Cation-exchange chromatography significantly cleared β-glucans. Furthermore, β-glucan leaching from the Planova 20N virus removal filter was reduced by increasing the flush volume (1 vs. 10 L/m2). β-glucan concentrations after filter flush with 10 L/m2 were consistently <10 pg/ml. No or only limited β-glucan clearance was attained via ultrafiltration/diafiltration (UF/DF). However, during the first run with monoclonal antibody (mAb) 4, β-glucan concentration in the UF/DF retentate was 10.8 pg/mg, potentially due to β-glucan leaching from the first run with a regenerated cellulose membrane. Overall, β-glucan levels in the final mAb drug substance were 1–12 pg/mg. Assuming high doses of 1,000–5,000 mg, a β-glucan contamination at 20 pg/mg would translate to 20–100 ng/dose, which is below the previously suggested threshold for product safety (≤500 ng/dose). 相似文献
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David Saleh Gang Wang Benedict Mueller Federico Rischawy Simon Kluters Joey Studts Jürgen Hubbuch 《Biotechnology progress》2021,37(1):e3081
Cation exchange chromatography (CEX) is an essential part of most monoclonal antibody (mAb) purification platforms. Process characterization and root cause investigation of chromatographic unit operations are performed using scale down models (SDM). SDM chromatography columns typically have the identical bed height as the respective manufacturing-scale, but a significantly reduced inner diameter. While SDMs enable process development demanding less material and time, their comparability to manufacturing-scale can be affected by variability in feed composition, mobile phase and resin properties, or dispersion effects depending on the chromatography system at hand. Mechanistic models can help to close gaps between scales and reduce experimental efforts compared to experimental SDM applications. In this study, a multicomponent steric mass-action (SMA) adsorption model was applied to the scale-up of a CEX polishing step. Based on chromatograms and elution pool data ranging from laboratory- to manufacturing-scale, the proposed modeling workflow enabled early identification of differences between scales, for example, system dispersion effects or ionic capacity variability. A multistage model qualification approach was introduced to measure the model quality and to understand the model's limitations across scales. The experimental SDM and the in silico model were qualified against large-scale data using the identical state of the art equivalence testing procedure. The mechanistic chromatography model avoided limitations of the SDM by capturing effects of bed height, loading density, feed composition, and mobile phase properties. The results demonstrate the applicability of mechanistic chromatography models as a possible alternative to conventional SDM approaches. 相似文献
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Ip Yuen K. Hiong Kum C. Teng Joey H. Q. Boo Mel V. Choo Celine Y. L. Wong Wai P. Chew Shit F. 《Coral reefs (Online)》2020,39(2):451-465
Coral Reefs - Giant clams flourish in nutrient-poor waters of tropical Indo-Pacific because they live in symbiosis with extracellular dinoflagellates (zooxanthellae) and receive photosynthates from... 相似文献
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