This study presents a combined experimental and numerical investigation of fiber transport and deposition in a realistic model of the female respiratory tract, extending to the seventh generation of branching. Numerical simulations were performed using the Euler-Lagrange Euler-Rotation (ELER) method, an efficient alternative to conventional Finite Volume Methods that benefits from explicit formulation and vast scalability, enabling fast parallelization on high-performance clusters. The ELER method was coupled with the Lattice Boltzmann Method (LBM) to simulate fiber dynamics under a realistic inspiratory flow profile. Experimental validation was conducted using an identical physical airway replica. The results demonstrated good agreement between simulations and experiments in the upper airways and trachea, with some discrepancies in the bifurcations, likely owing to the challenges of modeling complex turbulent flow with ELER. This method is more accurate than corresponding effective diameter simulations. Deposition patterns were analyzed as a function of fiber dimensions, revealing higher accuracy of the ELER method for smaller particles and confirming the tendency of higher aspect ratio fibers to penetrate deeper into the lungs. The orientation-dependent deposition mechanism was deployed, underscoring the importance of solving the actual orientations of the fibers. While advancing our understanding of fiber transport in female airways, the findings also reveal limitations in current numerical techniques, particularly in bifurcations. This study emphasizes the distinct behavior of fibrous versus spherical particles, with fibers exhibiting a greater propensity to reach deeper lung regions, which has significant implications for inhalation toxicology and drug delivery.

• Klíčová slova
• Deposition, Euler–Lagrange Euler-rotation, Female airway geometry, Fiber transport, In silico, In vitro, Lattice Boltzmann method,
• Publikační typ
• časopisecké články MeSH

The main lipid compounds of the outermost layer of human skin are ceramides (CERs), free fatty acids, and cholesterol. Although numerous studies performed in the past could demonstrate the importance of these lipids for an intact skin barrier function, knowledge about the impact of each single component on the lamellar lipid films is still lacking. Especially, the CERs are a very heterogeneous group with high relevance for a proper barrier. It was found that the reason for the high stability of the lamellae is related to the lipid structure and function, with the type and extent of interactions between the head groups of the individual CER subspecies being particularly important. Elucidating these at the molecular level could help us to understand CER phase behavior in general. Using grazing incidence X-ray diffraction and measurements of Langmuir isotherms, the current work investigated the lateral packing of the monolayers of different subclasses of C18:0 CERs at air-water interfaces, including phytosphingosine, sphingosine, and dihydrosphingosine CERs, all with either α-hydroxy and nonhydroxy N-acylated fatty acyl. We were able to observe clear effects of the minimal differences in the polar headgroup structures of the sphingoid bases, with respect to the number and position of hydroxyl groups and double bonds, on the CER arrangement regarding the compressibility and structure of the films they formed, revealing that the hydroxyl group at the C4 of the phytosphingosine CERs leads not only to the formation of a hydrogen bond network but also to a stable suprastructure, which might be of high benefit for the barrier properties of intact skin.

• MeSH
• ceramidy * chemie   MeSH
• difrakce rentgenového záření MeSH
• lidé MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ceramidy * MeSH

Preparative chromatography for purification of sugars has found numerous applications in food processing and biochemical industries. Parameter estimation leading to robust modelling and model-based design are essential for transferring this technology into industrial practice. This study examines the Equilibrium Dispersive model with a non-linear isotherm and the formulation of apparent dispersion based on the Bodenstein number. A parameter estimation workflow is proposed, incorporating chromatography-specific algorithmic data preprocessing and a curve uncertainty scoring system, enabling the simultaneous utilization of data from pulse-feed experiments conducted under varying conditions. A bilevel optimization scheme is introduced, leading to increased performance and robustness. The introduction of parameter bounding and initialization eliminates arbitrariness in the process. Experiments on the chromatographic separation of a d-glucose and sucrose mixture, performed under different flow rates and feed loads using an anion-exchange resin, were conducted. Lab-scale experiments were used for parameter estimation, supported by subsequent identifiability and sensitivity analyses. Scaling-up predictions of the calibrated model were evaluated by experimental data from a 2-meter-long pilot-scale column. The results demonstrate the benefits of the proposed modeling and parameter estimation framework, as well as the sufficient predictive accuracy of the calibrated model under the conditions of scaled-up flow rates and column dimensions.

• Klíčová slova
• Equilibrium dispersive model, Parameter estimation and bilevel optimization, Preparative chromatography, Process scale-up modelling and pilot plant evaluation, Sugars separation,
• Publikační typ
• časopisecké články MeSH

The rate coding hypothesis is the oldest and still one of the most accepted hypotheses of neural coding. Consequently, many approaches have been devised for the firing rate estimation, ranging from simple binning of the time axis to advanced statistical methods. Nonetheless the concept of firing rate, while informally understood, can be mathematically defined in several distinct ways. These definitions may yield mutually incompatible results unless implemented properly. Recently it has been shown that the notions of the instantaneous and the classical firing rates can be made compatible, at least in terms of their averages, by carefully discerning the time instant at which the neuronal activity is observed. In this paper we revisit the properties of instantaneous interspike intervals in order to derive several novel firing rate estimators, which are free of additional assumptions or parameters and their temporal resolution is 'locally self-adaptive'. The estimators are simple to implement and are numerically efficient even for very large sets of data.

• Klíčová slova
• Big data, Estimator, Firing rate, Spike train,
• MeSH
• akční potenciály * fyziologie   MeSH
• lidé MeSH
• modely neurologické * MeSH
• neurony * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The biogenesis of Photosystem II is a complicated process requiring numerous auxiliary factors to assist in all steps of its assembly. The cyanobacterial protein Ycf39 forms a stress-induced complex with 2 small chlorophyll-binding, High-light-inducible proteins C and D (HliC and HliD), and has been reported to participate in the insertion of chlorophyll molecules into the central D1 subunit of Photosystem II. However, how this process is organized remains unknown. Here, we show that Ycf39 and both HliC and HliD can form distinct complexes with chlorophyll synthase (ChlG) in the model cyanobacterium Synechocystis sp. PCC 6803. We isolated and characterized ChlG complexes from various strains grown under different conditions and provide a mechanistic view of the docking of Ycf39 to ChlG via HliD and the structural role of HliC. In the absence of stress, chlorophyll is produced by the ChlG-HliD2-ChlG complex, which is stabilized by chlorophyll and zeaxanthin molecules bound to the HliD homodimer. The switch to high light leads to stress pressure and greatly elevated synthesis of HliC, resulting in the replacement of HliD homodimers with HliC-HliD heterodimers. Unlike HliD, HliC cannot interact directly with ChlG or Ycf39. Therefore, the original ChlG-HliD2-ChlG complex is converted into a ChlG-HliD-HliC hetero-trimer that presumably binds transiently to Ycf39 and the nascent D1 polypeptide. We speculate that this molecular machinery promotes the delivery of chlorophyll to D1 upon high-light-induced chlorophyll deficiency. The HliD homodimers formed under standard, nonstress growth conditions and attached to ChlG could serve as an emergency chlorophyll reserve.

• MeSH
• bakteriální proteiny * metabolismus   genetika   MeSH
• chlorofyl metabolismus   MeSH
• fotosystém II (proteinový komplex) * metabolismus   MeSH
• ligasy tvořící vazby C-O * metabolismus   genetika   MeSH
• světlo * MeSH
• světlosběrné proteinové komplexy MeSH
• Synechocystis * metabolismus   účinky záření   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bakteriální proteiny * MeSH
• chlorofyl MeSH
• chlorophyll synthetase MeSH Prohlížeč
• fotosystém II (proteinový komplex) * MeSH
• high light-inducible protein, cyanobacteria MeSH Prohlížeč
• ligasy tvořící vazby C-O * MeSH
• světlosběrné proteinové komplexy MeSH

Alzheimer's disease is a neurodegenerative disorder characterized by two hallmarks: amyloid beta plaques and neurofibrillary tangles. The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor involved in the pathophysiology of various diseases including cancer, diabetes, cardiovascular diseases, and Alzheimer's disease (AD). Therefore, targeting RAGE could be an effective strategy to block RAGE signaling pathways. The present study aims to identify potential RAGE inhibitors against AD through comprehensive in-silico approaches. A total of 708,580 compounds were screened from numerous databases using structure-based virtual screening and ADMET evaluation. Further, the molecules with good glide scores were assessed by molecular docking studies. Subsequently, the top six ligands were subjected to molecular dynamic (MD) simulations for 100 ns and binding free energy calculations to check their stability with RAGE (PDB: 6XQ3). The per-residue decomposition analysis revealed that specific residues namely, GLY_20, ALA_21, LYS_39, GLU_50, LYS_52, ARG_98, GLN_100, LYS_110, ASN_112, and ARG_198 played a key role in the binding process. Furthermore, the trajectory analysis (DCCM and PCA) analyzed the dominant motions of residues and predicted the stability of protein-ligand complexes. In conclusion, the Hit-6 compound could be a promising candidate for targeting RAGE and deserves further consideration as an anti-Alzheimer drug.

• Klíčová slova
• Alzheimer’s disease, MM-GBSA, Molecular dynamics, RAGE inhibitors, Virtual screening,
• MeSH
• Alzheimerova nemoc * farmakoterapie   metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• počítačová simulace MeSH
• receptor pro konečné produkty pokročilé glykace * antagonisté a inhibitory   chemie   metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ligandy MeSH
• receptor pro konečné produkty pokročilé glykace * MeSH

This study investigates the effects of post-curing temperatures on the tensile properties of hybrid basalt-jute-glass-carbon fiber-reinforced polymers (FRPs). Composite specimens were post-cured at 60 °C and 100 °C for 60 min, and their tensile behavior was assessed using a servo-hydraulic testing machine. Numerical simulations using the Abaqus software V6.14 were also conducted to compare experimental and computational results. The findings indicate that post-curing heat treatment enhances ductility due to increased polymer cross-linking, but excessive heat treatment at 100 °C negatively impacts elongation at fracture. The results revealed that specimens post-cured at 60 °C exhibited the optimal balance between strength and ductility, with increased elongation and moderate tensile strength. However, at 100 °C, while tensile strength improved in some cases, a significant decrease in elasticity and an increased risk of brittleness were observed, suggesting that extreme heat treatment may degrade polymer integrity. Natural fiber composites, particularly jute-based samples, outperformed synthetic composites in terms of elongation and overall mechanical stability. The numerical simulations provided further insights but showed discrepancies with experimental results, mainly due to fiber property variations and fabric waviness, underscoring the challenges of accurately modeling woven composites. The study highlights the importance of controlled post-curing temperatures in optimizing the mechanical performance of FRP composites, with 60 °C identified as the most effective condition for achieving a favorable balance between tensile strength, flexibility, and material durability. These findings offer valuable insights for material scientists and engineers working on the development of high-performance composite materials for structural and industrial applications.

• Klíčová slova
• basalt, carbon, composites, epoxy, fiberglass, hybrid, jute, temperature, tensile,
• Publikační typ
• časopisecké články MeSH

The research focuses on optical solitons and employs the generalized auxiliary equation technique to obtain soliton resolutions for the nonlinear Kairat-X equation. This equation considers wave number groups influenced by time and velocity dispersion in non-linear mediums. Because of their stability and numerous uses in signal processing, telecommunications, and quantum physics, optical solitons are appreciated. Novel periodic, exponential, and other soliton solutions are shown in the work, and the dynamics of the model are thoroughly examined using phase portraits, quasi-periodic patterns, Lyapunov exponents, 3D attractors, 2D power spectra, and sensitivity analysis. Various simulations show how noise intensity variations affect system sensitivity and instability through the assessment of stochastic sensitivity along with Poincaré, and Lyapunov analysis. These results provide a significant addition to the discipline.

• Klíčová slova
• Chaos, Lyapunov exponent, Multistability, Sensitivity analysis,
• Publikační typ
• časopisecké články MeSH

Cell communication systems based on polypeptide ligands use transmembrane receptors to transmit signals across the plasma membrane. In their biogenesis, receptors depend on the endoplasmic reticulum (ER)-Golgi system for folding, maturation, transport and localization to the cell surface. ER stress, caused by protein overproduction and misfolding, is a well-known pathology in neurodegeneration, cancer and numerous other diseases. How ER stress affects cell communication via transmembrane receptors is largely unknown. In disease models of multiple myeloma, chronic lymphocytic leukemia and osteogenesis imperfecta, we show that ER stress leads to loss of the mature transmembrane receptors FGFR3, ROR1, FGFR1, LRP6, FZD5 and PTH1R at the cell surface, resulting in impaired downstream signaling. This is caused by downregulation of receptor production and increased intracellular retention of immature receptor forms. Reduction of ER stress by treatment of cells with the chemical chaperone tauroursodeoxycholic acid or by expression of the chaperone protein BiP resulted in restoration of receptor maturation and signaling. We show a previously unappreciated pathological effect of ER stress; impaired cellular communication due to altered receptor processing. Our findings have implications for disease mechanisms related to ER stress and are particularly important when receptor-based pharmacological approaches are used for treatment.

• Klíčová slova
• ER, Endoplasmic reticulum, Impaired, Receptor, Signaling, Stress, Transmembrane,
• MeSH
• chaperon endoplazmatického retikula BiP MeSH
• kyselina taurochenodeoxycholová farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• receptory buněčného povrchu * metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• stres endoplazmatického retikula * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chaperon endoplazmatického retikula BiP MeSH
• kyselina taurochenodeoxycholová MeSH
• receptory buněčného povrchu * MeSH
• ursodoxicoltaurine MeSH Prohlížeč

This research presents the results of a combined numerical and experimental study of the thermal decomposition behavior of copolymers based on polypropylene glycol fumarate phthalate. The thermal decomposition of polymers plays a key role in various fields, such as waste recycling and energy recovery, and in the development of new materials. The objective of this study is to model the degradation kinetics using thermogravimetric data, matrix-based numerical methods, and quantum chemical calculations. To solve the resulting systems of linear algebraic equations (SLAEs), matrix decomposition algorithms (QR, SVD, and Cholesky) were employed, which enabled the determination of activation energy values for the process. Comparison of the activation energy (Ea) results obtained using the decomposition method of Cholesky (207.21 kJ/mol), normal equations (205.22 kJ/mol), singular value decomposition (206.23 kJ/mol), and QR decomposition (206.23 kJ/mol) showed minor changes that were associated with the features of each method. Quantum chemical calculations based on density functional theory (DFT) at the B3LYP/6-31G(d) level were performed to analyze the molecular structure and interpret the IR spectra. This study establishes that the content of functional groups (ether and ester) and the type of chemical bonds exert critical influences on the decomposition mechanism and associated thermal parameters. The results confirm that the polymer's structural architecture governs its thermal stability. The scientific novelty of this work lies in the integration of numerical approximation methods and quantum chemical analysis for investigating the thermal behavior of polymers. This approach is applied for the first time to copolymers of this composition and may be employed in the design of heat-resistant materials for agricultural and environmental applications.

• Klíčová slova
• matrix, polymer, polymer degradation, polypropylene glycol fumarate phthalate, thermodynamic characteristics,
• Publikační typ
• časopisecké články MeSH