Search

Abstract Objective Infantile spasm syndrome (ISS) is an epileptic encephalopathy without established treatment after the failure to standard of care based on steroids and vigabatrin. Converging lines of evidence indicating a role of NR2B subunits of the N‐methyl‐D‐aspartate (NMDA) receptor on the onset of spams in ISS patients, prompted us to test radiprodil, a negative allosteric NR2B modulator in preclinical seizure models and in infants with ISS. Methods Radiprodil has been tested in three models, including pentylenetetrazole‐induced seizures in rats across different postnatal (PN) ages. Three infants with ISS have been included in a phase 1b escalating repeated dose study. Results Radiprodil showed the largest protective seizure effects in juvenile rats (maximum at PN12, corresponding to late infancy in humans). Three infants resistant to a combination of vigabatrin and prednisolone received individually titrated doses of radiprodil for up to 34 days. Radiprodil was safe and well tolerated in all three infants, and showed the expected pharmacokinetic profile. One infant became spasm‐free and two showed clinical improvement without reaching spasm‐freedom. After radiprodil withdrawal, the one infant continued to be spasm‐free, while the two others experienced seizure worsening requiring the use of the ketogenic diet and other antiepileptic drugs. Interpretation Radiprodil showed prominent anti‐seizure effect in juvenile animals, consistent with the prevalent expression of NR2B subunit of the NMDA receptor at this age in both rodents and humans. The clinical testing, although preliminary, showed that radiprodil is associated with a good safety and pharmacokinetic profile, and with the potential to control epileptic spasms.

Here, the authors use atomic force microscopy under ultra-high vacuum conditions to study intramolecular single electron transfer within a single molecule. This allows them to investigate energy dissipation process related to the electron transfer as a function of temperature.

The blockchain technology is currently penetrating different areas of the modern Information and Communications Technology community. Most of the devices involved in blockchain-related processes are specially designed targeting only the mining aspect, i.e., solving the computational puzzle task. At the same time, the use of wearable and mobile devices may also become a part of eCommerce blockchain operation, especially during the on-charge time. The paper considers the possibility of using a large number of constrained devices to support the operation of the blockchain with a low impact on battery consumption. The utilization of such devices is expected to improve the system efficiency as well as to attract a more substantial number of users. This paper contributes to the body of knowledge with a survey of the main applications of blockchain for smartphones along with existing mobile blockchain projects. It also proposes a novel consensus protocol based on a combination of Proof-of-Work (PoW), Proof-of-Activity (PoA), and Proof-of-Stake (PoS) algorithms for efficient and on-the-fly utilization on resource-constrained devices. The system was deployed in a worldwide testnet with more than two thousand smartphones and compared with other projects from the user-experienced metrics perspective. The results prove that the utilization of PoA systems on a smartphone does not significantly affect the lifetime of the smartphone battery while existing methods based on PoW have a tremendous negative impact. Finally, the main open challenges and future investigation directions are outlined.

With the proliferation of machine-to-machine (M2M) communication in the course of the last decade, the importance of low-power wide-area network (LPWAN) technologies intensifies. However, the abundance of accurate propagation models proposed for these systems by standardization bodies, vendors, and research community hampers the deployment planning. In this paper, we question the selection of accurate propagation models for Narrowband IoT (NB-IoT), LoRaWAN, and Sigfox LPWAN technologies, based on extensive measurement campaign in two mid-size European cities. Our results demonstrate that none of the state-of-the-art models can accurately describe the propagation of LPWAN radio signals in an urban environment. For this reason, we propose enhancements to the selected models based on our experimental measurements. Performing the fine-tuning of the propagation models for one of the cities, we select Ericsson Urban (NB-IoT, LoRaWAN) and 3GPP (Sigfox) models as the ones providing the closest match. Finally, we proceed to perform cross-validation of the propagation models using the data set for another city. The tuned models demonstrate an excellent match with the real data in the cross-validation phase. They outperform their competitors by at least 20-80% in terms of relative deviation from the measured signal levels presenting the accurate option for NB-IoT, LoRaWAN, and Sigfox deployments planning in mid-size cities.

The infection mechanism and pathogenicity of Human T-lymphotropic virus 1 (HTLV-1) are ambiguously known for hundreds of years. Our knowledge about this virus is recently emerging. The purpose of the study is to design a vaccine targeting the envelope glycoprotein, GP62, an outer membrane protein of HTLV-1 that has an increased number of epitope binding sites. Data collection, clustering and multiple sequence alignment of HTLV-1 glycoprotein B, variability analysis of envelope Glycoprotein GP62 of HTLV-1, population protection coverage, HLA-epitope binding prediction, and B-cell epitope prediction were performed to predict an effective vaccine. Among all the predicted peptides, ALQTGITLV and VPSSSTPL epitopes interact with three MHC alleles. The summative population protection coverage worldwide by these epitopes as vaccine candidates was found nearly 70%. The docking analysis revealed that ALQTGITLV and VPSSSTPL epitopes interact strongly with the epitope-binding groove of HLA-A*02:03, and HLA-B*35:01, respectively, as this HLA molecule was found common with which every predicted epitope interacts. Molecular dynamics simulations of the docked complexes show they form stable complexes. So, these potential epitopes might pave the way for vaccine development against HTLV-1.

Background Extracellular vesicles are released into body fluids from the majority of, if not all, cell types. Because their secretion and specific cargo (e.g., proteins) varies according to pathology, extracellular vesicles may prove a rich source of biomarkers. However, their biological and pathophysiological functions are poorly understood in hematological malignancies. Objective Here, we investigated proteome changes in the exosome-rich fraction of the plasma of myelodysplastic syndrome patients and healthy donors. Methods Exosome-rich fraction of the plasma was isolated using ExoQuick™: proteomes were compared and statistically processed; proteins were identified by nanoLC-MS/MS and verified using the ExoCarta and QuickGO databases. Mann-Whitney and Spearman analyses were used to statistically analyze the data. 2D western blot was used to monitor clusterin proteoforms. Results Statistical analyses of the data highlighted clusterin alterations as the most significant. 2D western blot showed that the clusterin changes were caused by posttranslational modifications. Moreover, there was a notable increase in the clusterin proteoform in the exosome-rich fraction of plasma of patients with more severe myelodysplastic syndrome; this corresponded with a simultaneous decrease in their plasma. Conclusions This specific clusterin proteoform seems to be a promising biomarker for myelodysplastic syndrome progression.

Brachypodium distachyon is a useful model organism for studying interaction of cereals with phytopathogenic fungi. The present study tested the possibility of a compatible interaction of B. distachyon with the endophytic fungus Microdochium bolleyi originated from wheat roots. There was evaluated the effect of this endophytic fungus on the intensity of the attack by pathogen Fusarium culmorum in B. distachyon and wheat, and also changes in expression of genes (in B. distachyon: BdChitinase1, BdPR1-5, BdLOX3, BdPAL, BdEIN3, and BdAOS; and in wheat: TaB2H2(chitinase), TaPR1.1, TaLOX, TaPAL, TaEIN2, and TaAOS) involved in defence against pathogens. Using light microscopy and newly developed specific primers was found to be root colonization of B. distachyon by the endophyte M. bolleyi. B. distachyon plants, as well as wheat inoculated with M. bolleyi showed significantly weaker symptoms on leaves from infection by fungus F. culmorum than did plants without the endophyte. Expression of genes BdPR1-5, BdChitinase1, and BdLOX3 in B. distachyon and of TaPR1.1 and TaB2H2 in wheat was upregulated after infection with F. culmorum. M. bolleyi-mediated resistance in B. distachyon was independent of the expression of the most tested genes. Taken together, the results of the present study show that B. distachyon can be used as a model host system for endophytic fungus M. bolleyi.

Proper respiratory tract protection is the key factor to limiting the rate of COVID-19 spread and providing a safe environment for health care workers. Traditional N95 (FFP2) respirators are not easy to regenerate and thus create certain financial and ecological burdens; moreover, their quality may vary significantly. A solution that would overcome these disadvantages is desirable. In this study a commercially available knit polyester fleece fabric was selected as the filter material, and a total of 25 filters of different areas and thicknesses were prepared. Then, the size-resolved filtration efficiency (40–400 nm) and pressure drop were evaluated at a volumetric flow rate of 95 L/min. We showed the excellent synergistic effect of expanding the filtration area and increasing the number of filtering layers on the filtration efficiency; a filter cartridge with 8 layers of knit polyester fabric with a surface area of 900 cm2 and sized 25 × 14 × 8 cm achieved filtration efficiencies of 98% at 95 L/min and 99.5% at 30 L/min. The assembled filter kit consists of a filter cartridge (14 Pa) carried in a small backpack connected to a half mask with a total pressure drop of 84 Pa at 95 L/min. In addition, it is reusable, and the filter material can be regenerated at least ten times by simple methods, such as boiling. We have demonstrated a novel approach for creating high-quality and easy-to-breathe-through respiratory protective equipment that reduces operating costs and is a green solution because it is easy to regenerate.

The three-layer electrode consisting of the inner, middle, and outer layers of polythiophene (PTh), polyaniline (PANI), and poly(neutral red) (PNR), respectively, was developed, characterized, and tested as a potentiometric sensor for citrates. The spectroscopic and morphological findings based on Raman spectroscopy and scanning electron microscopy, respectively, demonstrated the consecutive formation of individual polymeric layers derived from PTh, PANI, and PNR in the multilayer system. The sharper and narrower peak profiles of PNR in the case of the three-layer system revealed a more organized structure than for the PNR layer alone. The PNR layer in such a novel arrangement shows the highest selectivity towards citrates among the tested carboxylates. Simultaneously, the unwanted influence of the underlying Pt surface is eliminated. The potentiometric characteristics of the proposed potentiometric sensor were examined at the detection of citrates in the real-world samples, compared with results for PNR simple electrode, and corresponded with the reference capillary electrophoresis and literature-based spectrophotometric method.

Layered sodium transition metal oxides belong to electrode materials for sodium-ion batteries that combine, in a better way, high performance with environmental requirements. However, their cycling stability is still far from desirable. Herein, we demonstrate a rational approach to control the cycling stability of sodium-deficient nickel manganese oxides, Na2/3Ni1/2Mn1/2O2, with two- and three-layer stacking through Al substitution and Al2O3 treatment. Layered Na2/3Ni1/2Mn1/2O2 oxide displays a limited ability to accommodate aluminum in its structure (i.e., up to 8 at. %). The substitution of Ni ions with electrochemically inactive Al3+ ions and keeping the amount of Mn ions in Na2/3Ni1/2−xAlxMn1/2O2 leads to the stabilization of the two-layer stacking and favors the participation of lattice oxygen in the electrochemical reaction in addition to Ni ions. This results in an increase in the specific capacity of the Al-substituted oxides. Furthermore, the kinetics of the cationic migration between layers occurring during oxide cycling was manipulated by oxide morphology. The best cycling stability is observed for Na2/3Ni0.42Al0.08Mn1/2O2 having a column-like morphology of stacked plate-like particles along the common faces. The treatment of the layered oxides with Al2O3 mitigates the Mn dissolution reaction during electrode cycling in the NaPF6-based electrolyte, thus contributing to a high cycling stability.

SARS-CoV-2 is a serious viral pathogen, and agents that inhibit its replication are in high demand. In the present work, we prepared two novel tryptanthrin derivates bearing a thiosemicarbazone moiety as potential antiviral agents. Both compounds displayed potent chelation activity against Fe(III/II) ion-associated COVID-19. The molecular docking results suggest that the compounds can display significant affinity towards SARS-CoV-2 papain-like proteases and SARS-CoV-2 main proteases. In addition, administering T8H-TSC can repress viral replication in the used model (Vero cells). Moreover, the therapeutic potential of the prepared compounds was predicted and analysed in terms of Lipinski’s rules, drug-likeness and drug score.

The paper presents the results of tensile and impact bending tests of 17%Cr-19%Mn-0.53%N high-nitrogen austenitic stainless steel in temperatures ranging from −196 to 20 °C. The steel microstructure and fracture surfaces were investigated using transmission and scanning electron microscopes, as well as X-ray diffraction analysis. The steel experiences a ductile-to-brittle transition (DBT); however, it possessed high tensile and impact strength characteristics, as well as the ductile fracture behavior at temperatures down to −114 °C. The correspondence between γ–ε microstructure and fracture surface morphologies was revealed after the tensile test at the temperature of −196 °C. In this case, the transgranular brittle and layered fracture surface was induced by ε-martensite formation. Under the impact bending test at −196 °C, the brittle intergranular fracture occurred at the elastic deflection stage without significant plastic strains, which preceded a failure due to the high internal stresses localized at the boundaries of the austenite grains. The stresses were induced by: (i) segregation of nitrogen atoms at the grain boundaries and in the near-boundary regions, (ii) quenching stresses, and (iii) reducing fcc lattice volume with the test temperature decrease and incorporation of nitrogen atoms into fcc austenite lattice. Anisotropy of residual stresses was revealed. This was manifested in the localization of elastic deformations of the fcc lattice and, consequently, the stress localization in -oriented grains; this is suggested to be the reason of brittle cleavage fracture.

V mobiliárním fondu zámku Kozel je uloženo malé torzo někdejší archeologické sbírky zámeckého muzea. Jedním z předmětů je kovová přilba typu Stromovka–Gnězdovo–Bojná, pravděpodobně z 9.–10. století. Stejně jako k ostatním nálezům ze zámku Kozel se k ní nedochovaly žádné původní informace nebo dokumentace. Cílem textu je porovnat tento dochovaný kus s analogiemi a vypátrat pravděpodobné okolnosti, které mohly vést k jeho nálezu, a jeho následné osudy.

This study deals with remembering of former "Leader of the Nation" František Ladislav Rieger in the annual years of his birth and death in 1918, 1938 and 1948. It will be focused on celebrations and commemorative acts, which took place in these years, and on the participation of the political representation, historians and Rieger's family. The main questions are: how Rieger's legacy was interpreted by different political parties and how Rieger's place in the Czech historical memory changed owing to the events happened in the years ending with eight which are traditionally considered as an important milestones of the modern Czech history.

Selenium is a micronutrient with a wide range of functions in animals, including humans, and in microorganisms such as microalgae. However, its role in plant metabolism remains ambiguous. Recent studies of Se supplementation showed that not only does it increase the content of the element itself, but also affects the accumulation of secondary metabolites in plants. The purpose of this review is to analyze and summarize the available data on the place of selenium in the secondary metabolism of plants and its effect on the accumulation of some plant metabolites (S- and N-containing secondary metabolites, terpenes, and phenolic compounds). In addition, possible molecular mechanisms and metabolic pathways underlying these effects are discussed. It should be noted that available data on the effect of Se on the accumulation of secondary metabolites are inconsistent and contradictory. According to some studies, selenium has a positive effect on the accumulation of certain metabolites, while other similar studies show a negative effect or no effect at all. The following aspects were identified as possible ways of regulating plant secondary metabolism by Se-supplementation: changes occurring in primary S/N metabolism, hormonal regulation, redox metabolism, as well as at the transcriptomic level of secondary metabolite biosynthesis. In all likelihood, the confusion in the results can be explained by other, more complex regulatory mechanisms in which selenium is involved and which affect the production of metabolites. Further study on the involvement of various forms of selenium in metabolic and signaling pathways is crucial for a deeper understanding of its role in growth, development, and health of plants, as well as the regulatory mechanisms behind them.

The reliability of numerical simulations of the structural response of nonhomogeneous materials to high velocity loadings is highly dependent on the used material model and parameters. For nonhomogeneous materials, such as fibres, reinforced concrete is widely used for the Winfrith model, but the question of appropriate material parameters for Ultra-High Performance Fibre Reinforcement Concrete (UHPFRC) under high velocity loadings is still open. The article deals with possible method of inverse identification of material parameters of a UHPFRC slab under blast loading for a Winfrith material model. Possible application is in the field of numerical simulation of protective or critical infrastructure response to blast loading. Experimental measurement of the time–deflection curve through laser scanning using the triangulation method gave us input data for an inverse identification phase conducted in Optislang software. Obtained material parameters from a given range are optimized for blast loading and their Pearson’s correlation coefficient provides us information about their significance for simulation.

The article is concerned with the experimental study of the crown fire effect on atmospheric transport processes: the formation of induced turbulence in the vicinity of the fire source and the transport of aerosol combustion products in the atmosphere surface layer at low altitudes. The studies were carried out in seminatural conditions on the reconstructed forest canopy. It was established that the structural characteristics of fluctuations of some atmosphere physical parameters in the case of a crown fire practically coincide with the obtained earlier values for a steppe fire. The highest concentration of aerosol combustion products was recorded at a height of 10–20 m from the ground surface. It was found that the largest number of aerosol particles formed during a crown fire had a particle diameter of 0.3 to 0.5 µm. As a result of experimental data extrapolation, it is concluded that an excess of aerosol concentration over the background value will be recorded at a distance of up to 2000 m for a given volume of burnt vegetation. It is of interest to further study these factors of the impact of wildfires on atmosphere under the conditions of a real large natural wildfire and determine the limiting distance of aerosol concentration excesses over background values.

Hyssop (Hyssopus officinalis L.) is an aromatic plant that is rich in various biologically active compounds and is widely used as a natural preservative and flavoring agent in the food and cosmetic industry and as a folk medicine against certain respiratory diseases. Despite the fact that selenium is not an essential trace element for plants, in a certain range of concentrations it can not only improve plant growth, but also increase the content of nutrients and biologically active compounds in plants. In the present study, the effect of treatment type (in a nutrient solution (NS) or by foliar application (FA)) and selenium (Se) concentration (2.0, 5.0, 10.0, 20.0, 40.0 μM) on the biomass, phenolic compounds, essential oil content, and antioxidant properties of hyssop grown in hydroponics was studied. Neither a toxic nor a beneficial effect of Se addition on the plants was observed. Selenium treatment significantly increased Se concentration in hyssop up to 38.35 μg g−1 (NS) and 34.86 μg g−1 (FA). The effect of selenium on the content of phenolic compounds, essential oil, and the antioxidant activity of hyssop depended on the applied selenium concentration. Hyssop treated with 10 μM Se (NS) and with 20 μM Se (FA) had a higher total content of hydroxycinnamic acids and higher contents of rosmarinic and chlorogenic acids, as well as a higher total content of phenolic compounds, higher content of essential oil, and higher antioxidant activity compared to other experimental plants. The results confirm the feasibility of selenium treatment of hyssop without reducing its production in order to enhance its nutritional and pharmaceutical properties.

From an economic and ecological standpoint, it is crucial to investigate the biologically active compounds of mistletoe plants, which are currently discarded by pruning urban mistletoe-infested trees. In the present study, the content of phenolic compounds, triterpenic and organic acids, as well as the antioxidant activity of the extracts of various mistletoe organs (leaves, stems, and fruits) collected from the most infested tree species were investigated. The mistletoe samples collected from Betula pendula, Acer platanoides, Crataegus monogyna, and Sorbus aucuparia showed the highest content of phenolic acids and flavonoids as well as antioxidant activity, as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and ferric reducing/antioxidant power (FRAP) assays. The leaves and stems of mistletoe from Tilia cordata were characterized by a high content of triterpenic acids (oleanolic, ursolic, and betulinic). The leaves and fruits of mistletoe plants from Populus nigra and Salix alba contained a high concentration of organic acids, particularly succinic and citric acids. Compared to stem and leaf extracts, the antioxidant activity of the mistletoe fruit extracts was 1.5–3 times higher. The obtained results indicate that mistletoe is a valuable raw material and can be used as a source of phenolic compounds and triterpenic and organic acids, as well as for producing extracts with antioxidant properties.

Modern biomedical science still experiences a significant need for easy and reliable sources of human cells. They are used to investigate pathological processes underlying disease, conduct pharmacological studies, and eventually applied as a therapeutic product in regenerative medicine. For decades, the pool of adult mesenchymal stem/stromal cells (MSCs) remains a promising source of stem and progenitor cells. Their isolation is more feasible than most other stem cells from human donors, yet they have a fair share of drawbacks. They include significant variability between donors, loss of potency, and transformation during long-term culture, which may impact the efficacy and reproducibility of research. One possible solution is a derivation of immortalized MSCs lines which receive a broader use in many medical and biological studies. In the present work, we demonstrated that in the most widely spread commercially available hTERT-immortalized MSCs cell line ASC52telo, sensitivity to hormonal stimuli was reduced, affecting their differentiation efficacy. Furthermore, we found that immortalized MSCs have impaired insulin-dependent and cAMP-dependent signaling, which impairs their adipogenic, but not osteogenic or chondrogenic, potential under experimental conditions. Our findings indicate that hTERT-immortalized MSCs may present a suboptimal choice for studies involving modeling or investigation of hormonal sensitivity.

Book review: Kuklík, J. Příběh československé ústavy 1920. I. díl: Příprava a přijetí ústavní listiny. Praha: Karolinum, 2020, 334 s.

Book review: Vojáček, L. První československý zákon: pokus o opožděný komentář. Praha: Wolters Kluwer, 2018, 379 p.

Multidimensional spectroscopic tools are important to explore the details of molecular dynamics. Here the authors use shaped pulses to demonstrate a 3D fluorescence spectroscopy method to extract the fourth and higher-order nonlinear responses in light-molecule interaction.

Light-harvesting antennas and efficient energy transfer enable photosynthesis in low light conditions in natural systems. Here the authors resolve exciton properties and the role of structural hierarchy in a model light-harvesting complex by excited-state 2D spectroscopy on a microfluidic platform.

NMR structure determination is challenging for proteins with a molecular weight above 30 kDa and atomic-resolution structure determination from cryo-EM data is currently not the rule. Here the authors describe an integrated structure determination approach that simultaneously uses NMR and EM data and allows them to determine the structure of the 468 kDa dodecameric aminopeptidase TET2 complex.

The focus of the research is to develop recommendations of smart specialization (SS) for Ukrainian policymakers using European approaches. The authors revealed that the main SS projects are presented in such sectors as agri-food, industrial modernization and energy. More than 12 EU countries were the plot for conducted analysis of SS, as a result of which the level of activity of each country was determined. The creation of consortiums, including SMEs, associations, universities and other participants, disclosed the successful way of SS realization. The structure of SME’s innovative potential in Ukraine was identified underlining their main characteristic features like types of innovations and innovative activity, differentiation according to enterprise size, their regional distribution. The authors explored lack of innovations on regional and national level and significant territorial disparities, which could be eliminated through policy implementation of regional SS. The existing legislative norms for possibility of SS implementation in Ukraine were analyzed due to correspondence with the EU ones. The analysis provides the opportunity to consider them only as general framework documents without any action plans and sectoral prioritization at all. The weak points of these law documents are emphasized. As a result of research, the authors developed recommendations presented by direct action plan for Ukrainian policymakers, which include such activities as underlining key priorities (especially ICT applicability in every SS project) and their correspondence with the EU ones; eliminating regional imbalances by focusing on innovation development and reorientation of some regions according to SS priorities; respecting regional existing capacities; providing organizational mechanism for cooperation of stakeholders and financial mechanism for SS support through the EU structural funds.

Introduction: Hormone changes during pregnancy lead to increased plasma lipid levels. When there is added disorder of lipid metabolism, this otherwise physiological change can cause extremely high triglyceride levels with potentionally life-threatening complications, such as non-biliary acute pancreatitis. Materials and Methods: We present a case report of a 27-year-old pregnant woman with familial hyperchylomicronemia and a history of 7 hypertriglyceridemia-induced acute pancreatitis attacks. Three attacks occured during her first pregnancy with the last one leading to its termination at 33 weeks owing to the death of the fetus. During her second pregnancy, standard treatment was not able to lower the triglyceride levels sufficiently and she suffered another acute pancreatitis attack. Therapeutic plasma exchange was therefore chosen as the treatment method. Results and Conclusion: Plasma exchange was succesful in the secondary prevention of acute pancreatitis attack and she delivered a healthy baby at 36 weeks of gestation. Treatment was very well tolerated by the mother and the fetus and this supports the use of apheresis as a safe and efficient method in tackling gestational hypertriglyceridemia.

Time-varying requirements of users on communication push mobile operators to increase density of base stations. However, the dense deployment of conventional static base stations (SBSs) is not always economical, for example, when periods of peak load are short and infrequent. In such cases, several flying base stations (FlyBSs) mounted on unmanned aerial vehicles can be seen as a convenient substitution for the dense deployment of SBSs. This paper focuses on maximization of user satisfaction with provided data rates. To this end, we propose an algorithm that associates users with the most suitable SBS/FlyBS and finds optimal positions of all FlyBSs. Furthermore, we investigate the performance of two proposed approaches for the joint association and positioning based on the genetic algorithm (GA) and particle swarm optimization (PSO). It is shown that both solutions improve the satisfaction of users with provided data rates in comparison with a competitive approach. We also demonstrate trade-offs between the GA and the PSO. While the PSO is of lower complexity than the GA, the GA requires a slightly lower number of active FlyBSs to serve the users.

The concept of device-to-device (D2D) communication, combining common radio frequency (RF) and visible light communication (VLC), is seen as a feasible way how to cope with spectrum crunch in the RF domain and how to maximize spectral efficiency in general. In this paper, our objective is to decide when RF should be utilized or if VLC proves to be the more profitable option. The selection between RF and VLC is defined as a multi-objective optimization problem targeting primarily to minimize the outage ratio while the secondary objective is to maximize the sum capacity of D2D pairs, composed by D2D transmitters and D2D receivers. To solve this problem, we design a centralized low-complexity heuristic algorithm selecting either RF or VLC band for each D2D pair relying on the mutual interference among the pairs. For interpretation of the mutual interference among the D2D pairs, we exploit directed weighted graphs adopted from the graph theory. The simulation results show that the proposed algorithm outperforms state-of-the-art algorithms in terms of the outage ratio, sum capacity and average energy efficiency. What is more, despite a very low complexity, the proposed algorithm reaches a close-to-optimum performance provided by the exhaustive search algorithm.

Significant attention has been devoted to the forced switch to distance learning as a result of the COVID-19 pandemic. However, some aspects of this issue that are very important for practice are still understudied. The aim of this study is to describe the development of an online-available screening tool which could help the teachers to identify the students at risk of lowered effectiveness during the distance learning and also to select an appropriate teaching approach for the given class. A complex survey involving 35 teachers of Czech language, German language, Mathematics, Physics and Geography, and more than 1400 of their students from 70 classes, was carried out. In the first step, we identified which out of the more than 100 potentially relevant variables have predictive value for the effectiveness of distance learning. Subsequently, a series of multilinear regression models enabling to quantify the impact of the individual variables on effectiveness and perceived usefulness of distance learning were developed. Moderation analysis was also used to model how suitable synchronous and asynchronous activities based on active learning are for classes with different characteristics. Based on the results of the models, a simple screening tool helping teachers to tailor their approach and strategy is being developed.

Biologically active substances from microalgae can exhibit antioxidant, immunostimulating, antibacterial, antiviral, antitumor, antihypertensive, regenerative, and neuroprotective effects. Lipid complexes of microalgae Chlorella vulgaris and Arthrospira platensis exhibit antibacterial activity and inhibit the growth of the Gram-positive strain Bacillus subtilis; the maximum zone of inhibition is 0.7 ± 0.03 cm at all concentrations. The carbohydrate-containing complex of C. vulgaris exhibits antibacterial activity, inhibits the growth of the Gram-positive strain B. subtilis, Bacillus pumilus; the maximum zone of inhibition is 3.5 ± 0.17 cm at all concentrations considered. The carbohydrate complex of A. platensis has antimicrobial activity against the Gram-negative strain of Escherichia coli at all concentrations, and the zone of inhibition is 2.0–3.0 cm. The presence of mythelenic, carbonyl groups, ester bonds between fatty acids and glycerol in lipid molecules, the stretching vibration of the phosphate group PO2, neutral lipids, glyco- and phospholipids, and unsaturated fatty acids, such as γ-linolenic, was revealed using FTIR spectra. Spectral peaks characteristic of saccharides were found, and there were cellulose and starch absorption bands, pyranose rings, and phenolic compounds. Both algae in this study had phenolic and alcohol components, which had high antibacterial activity. Microalgae can be used as biologically active food additives and/or as an alternative to antibiotic feed in animal husbandry due to their antibacterial properties.

IL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts 5 and 6 (meta and para) bearing indole moieties. Molecular docking studies showed that both compounds have the potential to bind IL-6R (free energy of binding −9.5 and −8.1 kcal/mol). The interaction with IL-6R was confirmed using microscale thermophoresis analyses, which revealed that both compounds had strong affinity for the IL-6R (experimentally determined dissociation constants 26.5 ± 2.5 nM and 304 ± 27.6 nM, respectively). In addition, both compounds were cytotoxic for a broad spectrum of cancer cell lines in micromolar concentrations, most likely due to their accumulation in mitochondria and inhibition of mitochondrial respiration. In summary, the structure motif of bis-pentamethinium salts represents a promising starting point for the design of novel multitargeting compounds with the potential to inhibit IL-6 signaling and simultaneously target mitochondrial metabolism in cancer cells.

Besides certain exceptions, healing of most tissues in the human body occurs via formation of scar tissue, rather than restoration of lost structures. After extensive acute injuries, this phenomenon substantially limits the possibility of lost function recovery and, in case of chronic injury, it leads to pathological remodeling of organs affected. Managing outcomes of damaged tissue repair is one of the main objectives of regenerative medicine. The first priority for reaching it is comparative investigation of mechanisms responsible for complete restoration of damaged tissues and mechanisms of scarring. However, human body tissues that undergo complete scar-free healing are scarce. The endometrium is a unique mucous membrane in the human body that heals without scarring after various injuries, as well as during each menstrual cycle (i.e., up to 400 times during a woman’s life). We hypothesized that absence of scarring during endometrial healing may be associated with tissue-specific features of its stromal cells (SCs) or their microenvironment, since SCs transform into myofibroblasts—the main effector link of scarring. We found that during healing of the endometrium, soluble factors are formed that inhibit the transition of SCs into myofibroblasts. Without influence of these factors, the SCs of the endometrium undergo transformation into myofibroblasts after transforming growth factor β1 (TGF-β1) treatment as well as the SCs from tissues that heal by scarring—skin or fat. However, unlike the latter, endometrial SCs organize extracellular matrix (ECM) in a specific way and are not prone to formation of bulky connective tissue structures. Thus, we may suggest that tissue-specific features of endometrial SCs along with effects of soluble factors secreted in utero during menstruation ensure scar-free healing of human endometrium.

Human protoporphyrinogen oxidase IX (hPPO) is an oxygen-dependent enzyme catalyzing the penultimate step in the heme biosynthesis pathway. Mutations in the enzyme are linked to variegate porphyria, an autosomal dominant metabolic disease. Here we investigated eukaryotic cells as alternative systems for heterologous expression of hPPO, as the use of a traditional bacterial-based system failed to produce several clinically relevant hPPO variants. Using bacterially-produced hPPO, we first analyzed the impact of N-terminal tags and various detergent on hPPO yield, and specific activity. Next, the established protocol was used to compare hPPO constructs heterologously expressed in mammalian HEK293T17 and insect Hi5 cells with prokaryotic overexpression. By attaching various fusion partners at the N- and C-termini of hPPO we also evaluated the influence of the size and positioning of fusion partners on expression levels, specific activity, and intracellular targeting of hPPO fusions in mammalian cells. Overall, our results suggest that while enzymatically active hPPO can be heterologously produced in eukaryotic systems, the limited availability of the intracellular FAD co-factor likely negatively influences yields of a correctly folded protein making thus the E.coli a system of choice for recombinant hPPO overproduction. At the same time, PPO overexpression in eukaryotic cells might be preferrable in cases when the effects of post-translational modifications (absent in bacteria) on target protein functions are studied.

Brain-derived neurotrophic factor (BDNF) is a classic neuroprotective and pro-regenerative factor in peripheral and central nervous tissue. Its ability to stimulate the restoration of damaged nerve and brain tissue after ischemic stroke and intraventricular hemorrhage has been demonstrated. However, the current concept of regeneration allows us to assert that one factor, even if essential, cannot be the sole contributor to this complex biological process. We have previously shown that urokinase-type plasminogen activator (uPA) complements BDNF activity and stimulates restoration of nervous tissue. Using a model of intracerebral hemorrhage in rats, we investigated the neurotrophic and neuroprotective effect of BDNF combined with uPA. The local simultaneous administration of BDNF and uPA provided effective neuroprotection of brain tissue after intracerebral hemorrhage, promoted survival of experimental animals and their neurological recovery, and decreased lesion volume. The study of cellular mechanisms of the observed neurotrophic effect of BDNF and uPA combination revealed both known mechanisms (neuronal survival and neurite growth) and new ones (microglial activation) that had not been shown for BDNF and uPA. Our findings support the concept of using combinations of biological factors with diverse but complementary mechanisms of action as a promising regenerative approach.

The reaction of twenty-five winter wheat cultivars frequently grown in the Czech Republic to inoculation with Oculimacula yallundae and Oculimacula acuformis was evaluated in small plot trials from 2019 to 2021. The eyespot infection assessment was carried out visually using symptoms on stem bases and quantitative real-time polymerase chain reaction (qPCR). The cultivars were also tested for the presence of the resistance gene Pch1 using the STS marker Xorw1. Statistical differences were found between cultivars and between years. The lowest mean level of eyespot infection (2019–2021) was visually observed in cultivar Annie, which possessed resistance gene Pch1, and in cultivar Julie. Cultivars Turandot and RGT Sacramento were the most susceptible to eyespot. The method qPCR was able to distinguish two eyespot pathogens. O. yallundae was detected in higher concentrations in inoculated plants compared with O. acuformis. The relationship between the eyespot symptoms and the pathogen’s DNA content in plant tissues followed a moderate linear regression only in 2021. The highest eyespot infection rate was in 2020 due to weather conditions suitable for the development of the disease.

The knife-edge method is an established technique for profiling of even tightly focused light beams. However, the straightforward implementation of this method fails if the materials and geometry of the knife-edges are not chosen carefully or, in particular, if knife-edges are used that are made of pure materials. Artifacts are introduced in these cases in the shape and position of the reconstructed beam profile due to the interaction of the light beam under study with the knife. Hence, corrections to the standard knife-edge evaluation method are required. Here we investigate the knife-edge method for highly focused radially and azimuthally polarized beams and their linearly polarized constituents. We introduce relative shifts for those constituents and report on the consistency with the case of a linearly polarized fundamental Gaussian beam. An adapted knife-edge reconstruction technique is presented and proof-of-concept tests are shown, demonstrating the reconstruction of beam profiles.

The presented work is dedicated to the numerical study of the aerodynamic characteristics of the helicopter rotor. Two approaches to modeling of the rotor are applied: the free wake model developed by the Authors with using steady airfoil characteristics and the Unsteady RANS method based on the Ansys Fluent software. The modes of hovering and horizontal flight in the range of advancing ratio μ = (0-0.45) are considered. The shapes of the rotor wake, the distributions of the normal force coefficient and the fields of inductive velocities for all considered flight modes are calculated. For a particular case with μ = 0.25 there is a comparison with experimental data. The time needed for calculation of the applied methods is estimated. Accuracy of the used methods in the framework of the solved task is analysed with taking into account used models assumptions. It is shown that in the range of μ = (0-0.25) the free wake model provides a fast and reliable calculation of the aerodynamic characteristics of the helicopter rotor. For values of μ > 0.35 it is necessary to take into account the unsteady characteristics of the airfoil.

Abstrakt: Cílem této teoreticko-metodologické studie je vymezit didaktický konstrukt dynamická místa kurikula, zasadit ho do širšího teoretického rámce, charakterizovat s ním spojené metody výzkumu a uvést příklady dobré praxe. V úvodní části příspěvku definujeme pojem dynamická místa a zasazujeme jej do kontextu etablovaných konstruktů jako je obsahová transformace nebo modernizace kurikula. V této části studie také diskutujeme roli formálního a neformálního vzdělávání při řešení dynamických míst kurikula. Další část příspěvku je zaměřena metodologicky a věnuje se různým způsobům vymezování dynamických míst oborů a jejich výběru a legitimizace pro následnou transformaci. Poslední část se věnuje příkladům dobré praxe. Představujeme zde dva návrhy řešení zjištěných dynamických míst z kurikula fyziky a zeměpisu pro ZŠ. Konstrukt dynamických míst je platný také pro kurikulum středních škol. V textu nicméně klademe důraz především na implementaci dynamických míst do kurikula základních škol, které se dotýká všech žáků. Dynamická místa kurikula v tomto textu představujeme jako potenciální spojnici mezi formálním a neformálním vzděláváním. Prvním důvodem je, že při procesu vymezování a výběru dynamických míst se nabízí spolupráce zástupců formálního vzdělávání (oboroví didaktici, učitelé z praxe) i vzdělávání neformálního (pracovníci science center a dalších institucí neformálního vzdělávání). Druhým důvodem je vysoký potenciál institucí neformálního vzdělávání pro ztvárnění dynamických míst díky dobře vybaveným expozicím a laboratořím. Skrze výukové programy nabízené institucemi neformálního vzdělávání školám tak může docházet k aktualizaci kurikula formálního vzdělávání.

Abstract Nanotheranostics, which combines optical multiplexed disease detection with therapeutic monitoring in a single modality, has the potential to propel the field of nanomedicine toward genuine personalized medicine. Currently employed mainstream modalities using gold nanoparticles (AuNPs) in diagnosis and treatment are limited by a lack of specificity and potential issues associated with systemic toxicity. Light‐mediated nanotheranostics offers a relatively non‐invasive alternative for cancer diagnosis and treatment by using AuNPs of specific shapes and sizes that absorb near infrared (NIR) light, inducing plasmon resonance for enhanced tumor detection and generating localized heat for tumor ablation. Over the last decade, significant progress has been made in the field of nanotheranostics, however the main biological and translational barriers to nanotheranostics leading to a new paradigm in anti‐cancer nanomedicine stem from the molecular complexities of cancer and an incomplete mechanistic understanding of utilization of Au‐NPs in living systems. This work provides a comprehensive overview on the biological, physical and translational barriers facing the development of nanotheranostics. It will also summarise the recent advances in engineering specific AuNPs, their unique characteristics and, importantly, tunability to achieve the desired optical/photothermal properties.

Homeotic genes (Hox) are universal regulators of the body patterning process in embryogenesis of metazoans. The Hox gene expression pattern (Hox code) retains in adult tissues and serves as a cellular positional identity marker. Despite previously existing notions that the Hox code is inherent in all stroma mesenchymal cells as a whole, recent studies have shown that the Hox code may be an attribute of a distinct subpopulation of adult resident mesenchymal stromal cells (MSC). Recent evidence allows suggesting a “non-canonical” role for Hox gene expression which is associated with renewal and regeneration in postnatal organs after damage. In tissues with high regenerative capacity, it has been shown that a special cell population is critical for these processes, a distinctive feature of which is the persistent expression of tissue-specific Hox genes. We believe that in the postnatal period Hox-positive subpopulation of resident MSC may serve as a unique regenerative reserve. These cells coordinate creation and maintenance of the correct structure of the stroma through a tissue-specific combination of mechanisms. In this article, we summarize data on the role of resident MSC with a tissue-specific pattern of Hox gene expression as regulators of correct tissue reconstruction after injury.

V mobiliárním fondu zámku Kozel se nachází kovový nánosník vyspělé konstrukce, jenž byl s oblibou upevňován na přilby především v pokročilém 14. století. Jedná se o starý nález bez adekvátní dokumentace a neznáme ani nálezové okolnosti ani místo nálezu. Jde ovšem o exemplář morfologicky i rozměrově téměř totožný s nedávno publikovaným nánosníkem z hradu Ronovce (Knápek–Macků 2016), přičemž kozelský nánosník je dochovaný v mnohem lepším stavu a je stále pohyblivý. Cílem tohoto příspěvku není znovu popisovat vývoj tohoto druhu militaria ve středověku, ale doplnit doposud neúplnou mozaiku o možnostech "sériové" výroby specifických předmětů – militarií ve 14. století.

ABSTRACT The posttranslational Ca2+-dependent “clip-and-link” activity of large repeat-in-toxin (RTX) proteins starts by Ca2+-dependent structural rearrangement of a highly conserved self-processing module (SPM). Subsequently, an internal aspartate-proline (Asp-Pro) peptide bond at the N-terminal end of SPM breaks, and the liberated C-terminal aspartyl residue can react with a free ε-amino group of an adjacent lysine residue to form a new isopeptide bond. Here, we report a solution structure of the calcium-loaded SPM (Ca-SPM) derived from the FrpC protein of Neisseria meningitidis. The Ca-SPM structure defines a unique protein architecture and provides structural insight into the autocatalytic cleavage of the Asp-Pro peptide bond through a “twisted-amide” activation. Furthermore, in-frame deletion of the SPM domain from the ApxIVA protein of Actinobacillus pleuropneumoniae attenuated the virulence of this porcine pathogen in a pig respiratory challenge model. We hypothesize that the Ca2+-dependent clip-and-link activity represents an unconventional strategy for Gram-negative pathogens to adhere to the host target cell surface. IMPORTANCE The Ca2+-dependent clip-and-link activity of large repeat-in-toxin (RTX) proteins is an exceptional posttranslational process in which an internal domain called a self-processing module (SPM) mediates Ca2+-dependent processing of a highly specific aspartate-proline (Asp-Pro) peptide bond and covalent linkage of the released aspartyl to an adjacent lysine residue through an isopeptide bond. Here, we report the solution structures of the Ca2+-loaded SPM (Ca-SPM) defining the mechanism of the autocatalytic cleavage of the Asp414-Pro415 peptide bond of the Neisseria meningitidis FrpC exoprotein. Moreover, deletion of the SPM domain in the ApxIVA protein, the FrpC homolog of Actinobacillus pleuropneumoniae, resulted in attenuation of virulence of the bacterium in a pig infection model, indicating that the Ca2+-dependent clip-and-link activity plays a role in the virulence of Gram-negative pathogens.

High-throughput DNA sequencing techniques enable time- and cost-effective sequencing of large portions of the genome. Instead of sequencing and annotating whole genomes, many phylogenetic studies focus sequencing effort on large sets of pre-selected loci, which further reduces costs and bioinformatic challenges while increasing coverage. One common approach that enriches loci before sequencing is often referred to as target sequence capture. This technique has been shown to be applicable to phylogenetic studies of greatly varying evolutionary depth. Moreover, it has proven to produce powerful, large multi-locus DNA sequence datasets suitable for phylogenetic analyses. However, target capture requires careful considerations, which may greatly affect the success of experiments. Here we provide a simple flowchart for designing phylogenomic target capture experiments. We discuss necessary decisions from the identification of target loci to the final bioinformatic processing of sequence data. We outline challenges and solutions related to the taxonomic scope, sample quality, and available genomic resources of target capture projects. We hope this review will serve as a useful roadmap for designing and carrying out successful phylogenetic target capture studies.

In order to identify reasons for treatment failures when using targeted therapies, we have analyzed the comprehensive molecular profiles of three relapsed, poor-prognosis Burkitt lymphoma cases. All three cases had resembling clinical presentation and histology and all three patients relapsed, but their outcomes differed significantly. The samples of their tumor tissue were analyzed using whole-exome sequencing, gene expression profiling, phosphoproteomic assays, and single-cell phosphoflow cytometry. These results explain different treatment responses of the three histologically identical but molecularly different tumors. Our findings support a personalized approach for patient with high risk, refractory, and rare diseases and may contribute to personalized and customized treatment efforts for patients with limited treatment options like relapsed/refractory Burkitt lymphoma.SummaryThe main aim of this study is to analyze three relapsed Burkitt lymphoma patients using a comprehensive molecular profiling, in order to explain their different outcomes and to propose a biomarker-based targeted treatment. In cases 1 and 3, the tumor tissue and the host were analyzed prospectively and appropriate target for the treatment was successfully implemented; however, in case 2, analyses become available only retrospectively and his empirically based rescue treatment did not hit the right target of his disease.

This study deals with the view of Václav Červinka, son-in-low of František Ladislav Rieger, administrator of Rieger's estate Maleč and a man of many intellectual interests, on radical changes of the Central Europe at the turn of the 20th century, especially destruction of traditional political, economic, social and cultural structures, outbreak of the First World War, collapse of the Austria-Hungary and estabilishment of the independent Czechoslovakia. It is shown, how Červinka, as a man who was closely tied to the traditional conservative policy and politicians of the end of the 19th century, evaluated all these changes and what was his reaction, e. g. in his literary work.

Oxidative stress in humans is related to various pathophysiological processes, which can manifest in numerous diseases including cancer, cardiovascular diseases, and Alzheimer's disease. On the atomistic level, oxidative stress causes posttranslational modifications, thus inducing structural and functional changes into the proteins structure. This study focuses on fibrinogen, a blood plasma protein that is frequently targeted by reagents causing posttranslational modifications in proteins. Fibrinogen was in vitro modified by three reagents, namely sodium hypochlorite, malondialdehyde, and 3-morpholinosydnonimine that mimic the oxidative stress in diseases. Newly induced posttranslational modifications were detected via mass spectrometry. Electron microscopy was used to visualize changes in the fibrin networks, which highlight the extent of disturbances in fibrinogen behavior after exposure to reagents. We used molecular dynamics simulations to observe the impact of selected posttranslational modifications on the fibrinogen structure at the atomistic level. In total, 154 posttranslational modifications were identified, 84 of them were in fibrinogen treated with hypochlorite, 51 resulted from a reaction of fibrinogen with malondialdehyde, and 19 were caused by 3-morpholinosydnonimine. Our data reveal that the stronger reagents induce more posttranslational modifications in the fibrinogen structure than the weaker ones, and they extensively alter the architecture of the fibrin network. Molecular dynamics simulations revealed that the effect of posttranslational modifications on fibrinogen secondary structure varies from negligible alternations to serious disruptions. Among the serious disruptions is the oxidation of γR375 resulting in the release of Ca2+ ion that is necessary for appropriate fibrin fiber formation. Folding of amino acids γE72-γN77 into a short α-helix is a result of oxidation of γP76 to glutamic acid. The study describes behaviour of fibrinogen coiled-coil connecter in the vicinity of plasmin and hementin cleavage sites.

A facultative parasite of cereals, Fusarium culmorum is a soil-, air- and seed-borne fungus causing foot and root rot, fusarium seedling blight, and especially Fusarium head blight, a spike disease leading to decreased yield and mycotoxin contamination of grain. In the present study, we tested changes in expression of wheat genes (B2H2, ICS, PAL, and PR2) involved in defence against diseases. We first compared expression of the analysed genes in seedlings of non-inoculated and artificially inoculated wheat (variety Bohemia). The second part of the experiment compared expression of these genes in seedlings grown under various treatment conditions. These treatments were chosen to determine the effects of prochloraz, sodium bicarbonate, ergosterol, aescin and potassium iodide on expression of the analysed defence genes. In addition to the inoculated and non-inoculated cultivar Bohemia, we additionally examined two other varieties of wheat with contrasting resistance to Fusarium sp. infection. These were the blue aleurone layer variety Scorpion that is susceptible to Fusarium sp. infection and variety V2-49-17 with yellow endosperm and partial resistance to Fusarium sp. infection. In this manner, we were able to compare potential effects of inductors upon defence gene expression among three varieties with different susceptibility to infection but also between inoculated and non-inoculated seedlings of a single variety. The lowest infection levels were detected in the sodium bicarbonate treatment. Sodium bicarbonate had not only negative influence on Fusarium growth but also positively affected expression of plant defence genes. Expression of the four marker genes shown to be important in plant defence was significantly affected by the treatments. The greatest upregulation in comparison to the water control was identified under all treatments for the B2H2 gene. Only expression of PAL under the ergosterol and prochloraz treatments were not statistically significant.