Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile

In industry Escherichia coli is the preferred host system for the heterologous biosynthesis of therapeutic proteins that do not need posttranslational modifications. In this report, the development of a robust high-cell-density fed-batch procedure for the efficient production of a therapeutic hormone is described. The strategy is to guide the process along a predefined profile of the total biomass that was derived from a given specific growth rate profile. This profile might have been built upon experience or derived from numerical process optimization. A surprisingly simple adaptive procedure correcting for deviations from the desired path was developed. In this way the batch-to-batch reproducibility can be drastically improved as compared to the process control strategies typically applied in industry. This applies not only to the biomass but, as the results clearly show, to the product titer also

Correlation of sonographic characteristics and pathomorphological findings in cases of early-stage cervical cancer: preliminary results.

Objectives: To correlate the sonographic two-dimensional (2D) gray-scale features with pathological findings in early-stage invasive cervical cancer. Methods: Eighteen patients with biopsy-confirmed invasive cervical carcinoma (stages IB1 IIA according to FIGO staging) who underwent surgery were enrolled in the study. Transvaginal 2D gray-scale sonography was performed in all of them at the Hospital of Kaunas University of Medicine prior to hysterectomy. The largest diameters of tumor mass, tumor shape, tumor area, as well as the deepest cervical stromal invasion and the largest thickness of tumorfree cervical stroma in sagittal and axial planes were correlated with their pathomorphological equivalents using Pearson correlation coefficients. Toshiba NICE and Canvas X Scientific Edition software packages were employed for the analysis and correlation of sonographic and pathomorphological images. The interobserver variability was evaluated by having two blinded sonologists interpret each examination and calculating kappa statistics. The intraobserver variability was assayed in nine patients at 24-h intervals. Results: At 2D gray-scale analysis 15 patients (83%) showed detectable tumor masses. The largest diameters of the tumor mass (maximum length, depth and width) measured at sonographic and pathomorphological examinations correlated well (R = 0.87, R = 0.89 and R = 0.76, respectively). The largest tumor area measured in both sagittal and axial planes also showed a strong correlation (R = 0.78 and R = 0.84, respectively). Poor correlation was seen in the deepest cervical stromal invasion (R = 0.14). A discrepancy of more than 10% of the tumor shape in the sagittal plane seen during sonography and pathomorphological examination occurred in seven cases (47%). Conclusions: Two-dimensional gray-scale sonography is accurate in the assessment of early-stage cervical cancer. This method should be considered in all patients with early-stage cervical cancer scheduled for radical treatment