The aim of this study is to develop mathematical 3D finite element (FE) models for numerical simulations of vibroacoustic properties of the human vocal tract after a tonsillectomy. Similar experimental studies are not easily realizable on living subjects. The FE models of the acoustic spaces corresponding to the human vocal tract for the Czech vowels /a:/ and /i:/ and the acoustic space around the human head were used in numerical simulations of phonation. The acoustic resonant characteristics of the FE models were studied using modal and transient analyses (excitation by a short pulse). Calculated results show that a tonsillectomy causes a frequency shift of the 3rd (down by approximately 180 Hz) and 4th (down by approximately 120 Hz) formants down to the lower frequencies for the vowel /a:/ and similarly for the 2nd, 4th and 5th formants for the vowel /i:/ (all down by approximately 100 Hz). Similar effects and results can be found in experimental studies in literature. The formant changes are dependent on the size of additional acoustic spaces that occur after a tonsillectomy. The verification of the model was performed on the recordings of patients before and after the tonsillectomy operation. Multi-Dimensional Voice Program (MDVP Advanced, KAY Elemetrics Corp.) was used for the comparing of the formant centre frequencies. Very small differences in the results of subjective evaluation of the voice before and after tonsillectomy were found.

• MeSH
• analýza metodou konečných prvků MeSH
• biologické modely * MeSH
• dospělí MeSH
• hlas fyziologie   MeSH
• lidé MeSH
• matematické výpočty počítačové MeSH
• mladiství MeSH
• počítačová simulace * MeSH
• poruchy hlasu etiologie   patofyziologie   MeSH
• tonzilektomie * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In our previous work, we designed and implemented a synthetic metabolic pathway for 1,2,3-trichloropropane (TCP) biodegradation in Escherichia coli. Significant effects of metabolic burden and toxicity exacerbation were observed on single cell and population levels. Deeper understanding of mechanisms underlying these effects is extremely important for metabolic engineering of efficient microbial cell factories for biotechnological processes. In this paper, we present a novel mathematical model of the pathway. The model addresses for the first time the combined effects of toxicity exacerbation and metabolic burden in the context of bacterial population growth. The model is calibrated with respect to the real data obtained with our original synthetically modified E. coli strain. Using the model, we explore the dynamics of the population growth along with the outcome of the TCP biodegradation pathway considering the toxicity exacerbation and metabolic burden. On the methodological side, we introduce a unique computational workflow utilising algorithmic methods of computer science for the particular modelling problem.

• Klíčová slova
• biodegradation, computational modelling, environmental pollutants, metabolic burden, population growth,
• Publikační typ
• časopisecké články MeSH

Mechanical restitution (MR) represents the time recovery of the heart muscle's ability to contract. Despite intensive research, some aspects of MR remain unclear. To describe MR in guinea pig cardiac muscle, we modified our published mathematical model of guinea pig ventricular cardiomyocyte and supplemented it with a description of cellular contraction. To achieve the best agreement between the model simulations and available experimental data, some model parameters were optimised. The model enables the simulation of the experimentally observed fast onset of recovery of action potential duration, L-type Ca2+ current amplitude, and isometric force. The performed simulations and analyses of model data showed that the high time constant of voltage-dependent inactivation of L-type Ca2+ channels used in previously published models (~ 600 ms at resting voltage) is not consistent with the initial steep rise of the MR curve in guinea pig cardiomyocytes. It also suggests that the adaptation rate of ryanodine receptors, which was set differently in the previous models, is fast (~ 100 s- 1). Finally, analysis of the effect of a 50% reduction in membrane currents on MR revealed a marked dependence on stimulation frequency. At 1 Hz, only the reduction of INaCa and INaK significantly affected the MR course.

• Klíčová slova
• Calcium current, Guinea pig cardiomyocyte, Mathematical model, Mechanical restitution, Ryanodine receptor,
• MeSH
• akční potenciály fyziologie   MeSH
• kardiomyocyty * fyziologie   metabolismus   MeSH
• kontrakce myokardu * fyziologie   MeSH
• modely kardiovaskulární * MeSH
• morčata MeSH
• počítačová simulace MeSH
• ryanodinový receptor vápníkového kanálu metabolismus   MeSH
• vápníkové kanály - typ L metabolismus   MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ryanodinový receptor vápníkového kanálu MeSH
• vápníkové kanály - typ L MeSH

Due to the rise in awareness of global warming, many attempts to increase efficiency in the automotive industry are becoming prevalent. Design optimization can be used to increase the efficiency of electric vehicles by reducing aerodynamic drag and lift. The main focus of this paper is to analyse and optimise the aerodynamic characteristics of an electric vehicle to improve efficiency of using computational fluid dynamics modelling. Multiple part modifications were used to improve the drag and lift of the electric hatchback, testing various designs and dimensions. The numerical model of the study was validated using previous experimental results obtained from the literature. Simulation results are analysed in detail, including velocity magnitude, drag coefficient, drag force and lift coefficient. The modifications achieved in this research succeeded in reducing drag and were validated through some appropriate sources. The final model has been assembled with all modifications and is represented in this research. The results show that the base model attained an aerodynamic drag coefficient of 0.464, while the final design achieved a reasonably better overall performance by recording a 10% reduction in the drag coefficient. Moreover, within individual comparison with the final model, the second model with front spitter had an insignificant improvement, limited to 1.17%, compared with 11.18% when the rear diffuser was involved separately. In addition, the lift coefficient was significantly reduced to 73%, providing better stabilities and accounting for the safety measurements, especially at high velocity. The prediction of the airflow improvement was visualised, including the pathline contours consistent with the solutions. These research results provide a considerable transformation in the transportation field and help reduce fuel expenses and global emissions.

• Klíčová slova
• aerodynamics, computational fluid dynamics, design, electric hatchback, electric vehicle, fuel efficiency, optimization,
• Publikační typ
• časopisecké články MeSH

In systems biology, models play a crucial role in understanding studied systems. There are many modelling approaches, among which rewriting systems provide a framework for describing systems on a mechanistic level. Describing biochemical processes often requires incorporating knowledge on an abstract level to simplify the system description or substitute the missing details. For this purpose, we present regulation mechanisms, an extension of this formalism with additional controls on the rewriting process. We introduce several regulation mechanisms and apply them to a rule-based language, a notation suitable for modelling biological phenomena. Finally, we demonstrate the usage of such regulations on several case studies from the biochemical domain.

• Klíčová slova
• Multiset rewriting, Regulations, Rule-based modelling, Systems biology,
• MeSH
• algoritmy * MeSH
• biologické modely * MeSH
• jazyk (prostředek komunikace) MeSH
• počítačová simulace MeSH
• systémová biologie MeSH
• Publikační typ
• časopisecké články MeSH

There is great interest in increasing proteins' stability to enhance their utility as biocatalysts, therapeutics, diagnostics and nanomaterials. Directed evolution is a powerful, but experimentally strenuous approach. Computational methods offer attractive alternatives. However, due to the limited reliability of predictions and potentially antagonistic effects of substitutions, only single-point mutations are usually predicted in silico, experimentally verified and then recombined in multiple-point mutants. Thus, substantial screening is still required. Here we present FireProt, a robust computational strategy for predicting highly stable multiple-point mutants that combines energy- and evolution-based approaches with smart filtering to identify additive stabilizing mutations. FireProt's reliability and applicability was demonstrated by validating its predictions against 656 mutations from the ProTherm database. We demonstrate that thermostability of the model enzymes haloalkane dehalogenase DhaA and γ-hexachlorocyclohexane dehydrochlorinase LinA can be substantially increased (ΔTm = 24°C and 21°C) by constructing and characterizing only a handful of multiple-point mutants. FireProt can be applied to any protein for which a tertiary structure and homologous sequences are available, and will facilitate the rapid development of robust proteins for biomedical and biotechnological applications.

• MeSH
• bodová mutace genetika   fyziologie   MeSH
• databáze genetické MeSH
• lyasy chemie   genetika   metabolismus   MeSH
• molekulární modely MeSH
• počítačová simulace MeSH
• proteinové inženýrství metody   MeSH
• stabilita enzymů genetika   MeSH
• teplota MeSH
• výpočetní biologie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lyasy MeSH

Purpose Phonations into a tube with the distal end either in the air or submerged in water are used for voice therapy. This study explores the effective mechanisms of these therapy methods. Method The study applied a physical model complemented by calculations from a computational model, and the results were compared to those that have been reported for humans. The effects of tube phonation on vocal tract resonances and oral pressure variation were studied. The relationships of transglottic pressure variation in time Ptrans ( t) versus glottal area variation in time GA( t) were constructed. Results The physical model revealed that, for the phonation on [u:] vowel through a glass resonance tube ending in the air, the 1st formant frequency ( F1 ) decreased by 67%, from 315 Hz to 105 Hz, thus slightly above the fundamental frequency ( F0 ) that was set to 90-94 Hz . For phonation through the tube into water, F1 decreased by 91%-92%, reaching 26-28 Hz, and the water bubbling frequency Fb ≅ 19-24 Hz was just below F1 . The relationships of Ptrans ( t) versus GA( t) clearly differentiate vowel phonation from both therapy methods, and show a physical background for voice therapy with tubes. It is shown that comparable results have been measured in humans during tube therapy. For the tube in air, F1 descends closer to F0 , whereas for the tube in water, the frequency Fb occurs close to the acoustic-mechanical resonance of the human vocal tract. Conclusion In both therapy methods, part of the airflow energy required for phonation is substituted by the acoustic energy utilizing the 1st acoustic resonance. Thus, less flow energy is needed for vocal fold vibration, which results in improved vocal efficiency. The effect can be stronger in water resistance therapy if the frequency Fb approaches the acoustic-mechanical resonance of the vocal tract, while simultaneously F0 is voluntarily changed close to F1.

• MeSH
• akustika řeči MeSH
• anatomické modely MeSH
• fonace fyziologie   MeSH
• glottis MeSH
• hlasový trénink MeSH
• lidé MeSH
• plíce fyziologie   MeSH
• počítačová simulace MeSH
• řečová terapie metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of models available to forecast the magnitude of dissolution rate improvement caused by co-milling. Therefore, this study endeavoured to quantitatively predict the increase in dissolution by co-milling based on drug properties. Using a biorelevant dissolution setup, a series of 29 structurally diverse and crystalline drugs were screened in co-milled and physically blended mixtures with Polyvinylpyrrolidone K25. Co-Milling Dissolution Ratios after 15 min (COMDR15 min) and 60 min (COMDR60 min) drug release were predicted by variable selection in the framework of a partial least squares (PLS) regression. The model forecasts the COMDR15 min (R2 = 0.82 and Q2 = 0.77) and COMDR60 min (R2 = 0.87 and Q2 = 0.84) with small differences in root mean square errors of training and test sets by selecting four drug properties. Based on three of these selected variables, applicable multiple linear regression equations were developed with a high predictive power of R2 = 0.83 (COMDR15 min) and R2 = 0.84 (COMDR60 min). The most influential predictor variable was the median drug particle size before milling, followed by the calculated drug logD6.5 value, the calculated molecular descriptor Kappa 3 and the apparent solubility of drugs after 24 h dissolution. The study demonstrates the feasibility of forecasting the dissolution rate improvements of poorly water-solube drugs through co-milling. These models can be applied as computational tools to guide formulation in early stage development.

• Klíčová slova
• Ball milling, Co-grinding, Co-milling, Dissolution rate enhancement, In silico modelling, Multiple linear regression, Partial least squares regression,
• MeSH
• léčivé přípravky chemie   MeSH
• metoda nejmenších čtverců MeSH
• počítačová simulace MeSH
• povidon chemie   MeSH
• příprava léků * metody   MeSH
• rozpustnost * MeSH
• uvolňování léčiv * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• léčivé přípravky MeSH
• povidon MeSH

Needle-shaped crystals are a common occurrence in many pharmaceutical and fine chemicals processes. Even if the particle size distribution (PSD) obtained in a crystallization step can be controlled by the crystal growth kinetics and hydrodynamic conditions, further fluid-solid separation steps such as filtration, filter washing, drying, and subsequent solids handling can often lead to uncontrolled changes in the PSD due to breakage. In this contribution we present a combined computational and experimental methodology for determining the breakage kernel and the daughter distribution functions of needle-shaped crystals, and for population balance modeling of their breakage. A discrete element model (DEM) of needle-shaped particle breakage was first used in order to find out the appropriate types of the breakage kernel and the daughter distribution functions. A population balance model of breakage was then formulated and used in conjunction with experimental data in order to determine the material-specific parameters appearing in the breakage functions. Quantitative agreement between simulation and experiment has been obtained.

• MeSH
• chemické modely * MeSH
• filtrace MeSH
• hydrodynamika MeSH
• krystalizace MeSH
• léčivé přípravky chemie   MeSH
• počítačová simulace * MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• léčivé přípravky MeSH

Protein engineering strategies aimed at constructing enzymes with novel or improved activities, specificities, and stabilities greatly benefit from in silico methods. Computational methods can be principally grouped into three main categories: bioinformatics; molecular modelling; and de novo design. Particularly de novo protein design is experiencing rapid development, resulting in more robust and reliable predictions. A recent trend in the field is to combine several computational approaches in an interactive manner and to complement them with structural analysis and directed evolution. A detailed investigation of designed catalysts provides valuable information on the structural basis of molecular recognition, biochemical catalysis, and natural protein evolution.

• MeSH
• enzymy genetika   MeSH
• lidé MeSH
• molekulární modely MeSH
• mutace MeSH
• proteinové inženýrství metody   MeSH
• stabilita enzymů MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• enzymy MeSH