Confidence intervals by constrained optimization-An algorithm and software package for practical identifiability analysis in systems biology.

Practical identifiability of Systems Biology models has received a lot of attention in recent scientific research. It addresses the crucial question for models' predictability: how accurately can the models' parameters be recovered from available experimental data. The methods based on profile likelihood are among the most reliable methods of practical identification. However, these methods are often computationally demanding or lead to inaccurate estimations of parameters' confidence intervals. Development of methods, which can accurately produce parameters' confidence intervals in reasonable computational time, is of utmost importance for Systems Biology and QSP modeling. We propose an algorithm Confidence Intervals by Constraint Optimization (CICO) based on profile likelihood, designed to speed-up confidence intervals estimation and reduce computational cost. The numerical implementation of the algorithm includes settings to control the accuracy of confidence intervals estimates. The algorithm was tested on a number of Systems Biology models, including Taxol treatment model and STAT5 Dimerization model, discussed in the current article. The CICO algorithm is implemented in a software package freely available in Julia (https://github.com/insysbio/LikelihoodProfiler.jl) and Python (https://github.com/insysbio/LikelihoodProfiler.py).

Early results of the use of ProRoot MT and Titan cement for furcation perforation repair--a comparative experimental study.

UNLABELLED: The aim of the present experimental study was to follow up the connective tissue response after using ProRoot MTA and Titan cement to repair furcation perforations in dogs. MATERIAL AND METHODS: Four animals aged 12 to 18 months were used in the study. Perforation defects were created in the center of the pulp chamber of mandibular premolars P2, P3 and P4, right and left. The defects on the left side were repaired with ProRoot MTA, and those on the right side--with Titan cement in all dogs. After 30 days bone fragments with teeth included were fixed in formalin and decalcified in 50% formic acid. Serial sections of 10 microm thickness were prepared, stained with hematoxylin and eosin and studied under light microscopy. RESULTS: The connective tissue response in the Titan cement repaired teeth was a fibrous capsule in contact with the material, with single or aggregated lymphocytes seen in the vicinity. The response to ProRoot MTA was similar, but the fibrous capsule was thinner and without any aggregation of lymphocytes. CONCLUSIONS: The connective tissue response was similar for both tested materials. The tissues tolerated both of them well; it formed a fibrous capsule, which is indicative of the start of a healing process.