elektronický časopis
Ranked model in the form of linear transformation of multivariate feature vectors on a line can reflect a causal order between liver diseases. A priori medical knowledge about order between liver diseases and clinical data sets has been used in the definition of the convex and piecewise linear (CPL) criterion function. The linear ranked transformations have been designed here through minimization of such CPL criterion functions.
Úvod: Charakter nosního proudění je zásadní pro bezproblémové nosní dýchání, stejně jako může být patofyziologickým podkladem symptomů nosních onemocnění (nosní neprůchodnost, sekrece, tvorba krust aj.). Je obtížné definovat jeden fyziologický charakter proudění, protože subjektivní potíže nemocných často nejsou v korelaci s objektivním nálezem. Pozornost je proto věnována studiu nosní aerodynamiky, pro které je v současnosti nejvíce využíváno počítačové modelování proudění, tzv. computational fluid dynamics (CFD). Metodika: Pro simulaci nosního proudění byl ve spolupráci s Vysokou školou báňskou (VŠB) vytvořen 3D model dle CT vyšetření nosní dutiny pacientky, která neměla potíže s nosním dýcháním ("fyziologická" nosní dutina). Výsledky: Dle získaných výsledků se liší proudění vzduchu v pravé a levé nosní dutině. Hlavní proud vzduchu lze pozorovat jak v dolním a dolní části společného průduchu, tak i ve středním a střední části společného průduchu. První výsledky se shodují se studiemi uvádějícími značné rozdíly v nosní aerodynamice mezi zdravými jedinci. Závěr: Počítačové modelování proudění vzduchu má potenciál být využíváno v klinické praxi, především ve funkční rinochirurgii.
Introduction: The pattern of the nasal airflow is crucial for normal nasal breathing as well as it can be a pathophysiological underlay of nasal symptoms (nasal obstruction, crusting etc). It is difficult to define one physiological airflow pattern because subjective symptoms of patients do not correlate with objective findings quite often. Nowadays, the computational fluid dynamics (CFD) is dominant way how to simulate and study nasal airflow. Methods: For nasal airflow simulation 3D model of nasal cavity was created according to CT scans of nasal cavity (patient had no problems with nasal breathing). The 3D model was created with the cooperation with Technical University of Ostrava. Results: Our first experience with CFD showed that there is a different airflow pattern between right and left nasal cavity. Major part of airflow was detected in inferior and inferior part of common meatus and also in the middle and in the middle part of common nasal meatus. These results support studies that declare differences in nasal aerodynamics among healthy adults. Conclusion: CFD has a potential to be used in clinical practice especially in functional rhinosurgery.
- Keywords
- nosní proudění,
- MeSH
- Convection MeSH
- Humans MeSH
- Nose * physiology MeSH
- Computer Simulation * MeSH
- Imaging, Three-Dimensional MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't 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
- Speech Acoustics MeSH
- Models, Anatomic MeSH
- Phonation physiology MeSH
- Glottis MeSH
- Voice Training MeSH
- Humans MeSH
- Lung physiology MeSH
- Computer Simulation MeSH
- Speech Therapy methods MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The aim of the study was to determine the relationship between implant-associated complications and Dynamic Hip Screw (DHS) placement in the femoral neck, based on a Finite Element (FE) Analysis. Very diverse implant failures and subsequent complications can be encountered after introduction of the DHS. We evaluated 308 dynamic hip screw osteosyntheses for pertrochanteric fractures in 297 patients. The ABAQUS 6.9 program was used for development of the FE model, and the analyses were performed in 5 modelled situations corresponding to five different screw locations. Complications occurred in 10% of patients and re-operation was necessary in 3.9%. The highest risk of implant failure was associated with the screw situation in the upper third of the femoral neck. Placing a dynamic hip screw in the middle third of the neck significantly reduced stresses in the plate and screw. The screw position in the upper third of the neck significantly increased these stresses. The finite element analysis confirmed our clinical experience that the optimum position of the dynamic hip screw is in the middle third of the femoral neck.
- MeSH
- Equipment Failure Analysis * methods statistics & numerical data MeSH
- Femoral Neck Fractures * surgery radiography MeSH
- Hip Fractures surgery radiography MeSH
- Bone Screws MeSH
- Middle Aged MeSH
- Humans MeSH
- Stress, Mechanical MeSH
- Computer Simulation MeSH
- Reoperation statistics & numerical data MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Fracture Fixation, Internal * methods instrumentation adverse effects MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
The anthropogenic toxic compound 1,2,3-trichloropropane is poorly degradable by natural enzymes. We have previously constructed the haloalkane dehalogenase DhaA31 by focused directed evolution ( Pavlova, M. et al. Nat. Chem. Biol. 2009 , 5 , 727 - 733 ), which is 32 times more active than the wild-type enzyme and is currently the most active variant known against that substrate. Recent evidence has shown that the structural basis responsible for the higher activity of DhaA31 was poorly understood. Here we have undertaken a comprehensive computational study of the main steps involved in the biocatalytic hydrolysis of 1,2,3-trichloropropane to decipher the structural basis for such enhancements. Using molecular dynamics and quantum mechanics approaches we have surveyed (i) the substrate binding, (ii) the formation of the reactive complex, (iii) the chemical step, and (iv) the release of the products. We showed that the binding of the substrate and its transport through the molecular tunnel to the active site is a relatively fast process. The cleavage of the carbon-halogen bond was previously identified as the rate-limiting step in the wild-type. Here we demonstrate that this step was enhanced in DhaA31 due to a significantly higher number of reactive configurations of the substrate and a decrease of the energy barrier to the SN2 reaction. C176Y and V245F were identified as the key mutations responsible for most of those improvements. The release of the alcohol product was found to be the rate-limiting step in DhaA31 primarily due to the C176Y mutation. Mutational dissection of DhaA31 and kinetic analysis of the intermediate mutants confirmed the theoretical observations. Overall, our comprehensive computational approach has unveiled mechanistic details of the catalytic cycle which will enable a balanced design of more efficient enzymes. This approach is applicable to deepen the biochemical knowledge of a large number of other systems and may contribute to robust strategies in the development of new biocatalysts.
- MeSH
- Biocatalysis * MeSH
- Hydrolases chemistry genetics metabolism MeSH
- Catalytic Domain MeSH
- Kinetics MeSH
- Mutation MeSH
- Computer Simulation * MeSH
- Rhodococcus enzymology MeSH
- Molecular Dynamics Simulation MeSH
- Molecular Docking Simulation MeSH
- Thermodynamics MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Interdisciplinary applied mathematics
1st ed. xliii, 634 s., barev. il.
elektronický časopis
- MeSH
- Models, Neurological MeSH
- Neurosciences instrumentation MeSH
- Computer Simulation MeSH
- Computing Methodologies MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- neurologie
- neurovědy
- NML Publication type
- elektronické časopisy
Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs not soluble in water, those with otherwise strong adverse effects, or very fragile ones such as nucleic acids. However, for the rational design of LNCs, a detailed understanding of the composition-structure-function relationships is missing. This review presents currently available computational methods for LNC investigation, screening, and design. The state-of-the-art physics-based approaches are described, with the focus on molecular dynamics simulations in all-atom and coarse-grained resolution. Their strengths and weaknesses are discussed, highlighting the aspects necessary for obtaining reliable results in the simulations. Furthermore, a machine learning, i.e., data-based learning, approach to the design of lipid-mediated API delivery is introduced. The data produced by the experimental and theoretical approaches provide valuable insights. Processing these data can help optimize the design of LNCs for better performance. In the final section of this Review, state-of-the-art of computer simulations of LNCs are reviewed, specifically addressing the compatibility of experimental and computational insights.
- MeSH
- Pharmaceutical Preparations chemistry MeSH
- Drug Delivery Systems methods MeSH
- Humans MeSH
- Lipids * chemistry MeSH
- Nanoparticles chemistry MeSH
- Drug Carriers chemistry MeSH
- Computer Simulation MeSH
- Molecular Dynamics Simulation * MeSH
- Machine Learning MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Evoked neural responses to sensory stimuli have been extensively investigated in humans and animal models both to enhance our understanding of brain function and to aid in clinical diagnosis of neurological and neuropsychiatric conditions. Recording and imaging techniques such as electroencephalography (EEG), magnetoencephalography (MEG), local field potentials (LFPs), and calcium imaging provide complementary information about different aspects of brain activity at different spatial and temporal scales. Modeling and simulations provide a way to integrate these different types of information to clarify underlying neural mechanisms. In this study, we aimed to shed light on the neural dynamics underlying auditory evoked responses by fitting a rate-based model to LFPs recorded via multi-contact electrodes which simultaneously sampled neural activity across cortical laminae. Recordings included neural population responses to best-frequency (BF) and non-BF tones at four representative sites in primary auditory cortex (A1) of awake monkeys. The model considered major neural populations of excitatory, parvalbumin-expressing (PV), and somatostatin-expressing (SOM) neurons across layers 2/3, 4, and 5/6. Unknown parameters, including the connection strength between the populations, were fitted to the data. Our results revealed similar population dynamics, fitted model parameters, predicted equivalent current dipoles (ECD), tuning curves, and lateral inhibition profiles across recording sites and animals, in spite of quite different extracellular current distributions. We found that PV firing rates were higher in BF than in non-BF responses, mainly due to different strengths of tonotopic thalamic input, whereas SOM firing rates were higher in non-BF than in BF responses due to lateral inhibition. In conclusion, we demonstrate the feasibility of the model-fitting approach in identifying the contributions of cell-type specific population activity to stimulus-evoked LFPs across cortical laminae, providing a foundation for further investigations into the dynamics of neural circuits underlying cortical sensory processing.
- MeSH
- Acoustic Stimulation methods MeSH
- Electroencephalography methods MeSH
- Haplorhini MeSH
- Humans MeSH
- Computer Simulation MeSH
- Evoked Potentials, Auditory physiology MeSH
- Auditory Cortex * physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, N.I.H., Extramural MeSH
