Turing (1937) introduces a model of code that is followed by other pioneers of computing machines (such as Flowers 1983, Eckert, Mauchly, Brainerd 1945 and others). One of them is John von Neumann, who defines the concept of optimal code in the context of the conception of EDVAC. He later uses it to build on in his theoretical considerations of the universal constructor (von Neumann 1966). Von Neumann (1963) further presents one of the first neural network models, in relation to the work of McCulloch and Pitts (1943), for both theoretical purposes (von Neumann probe) and practical applications (computer architecture of EDVAC). The aim of this paper is (1) to describe the differences between Turing's and von Neumann's conceptualizations of code and the mechanical computing model. Between von Neumann's abstract technical conception (von Neumann 1963 and 1966) and Turing's more concrete biochemical conception (Turing 1952). Furthermore, (2) we want to answer the question why these influential models of mechanisms (predominantly in computer science) have so far been ignored by philosophers of the new mechanism (Machamer, Darden, Craver 2000, Glennan 2017). We will show that these classical models of machines are not only compatible with the new mechanism, but moreover complement it, since they represent a completely separate type of model of mechanism, alongside producing, maintaining and underlying (Zámečník 2021). The final (3) and main goal of our paper will be an attempt to relate von Neumann's and Turing's notion of mechanism to Barbieri's notion of extended mechanism (Barbieri 2015).

• Klíčová slova
• Code biology, Extended mechanism, New mechanism, Turing machine, von Neumann probe,
• MeSH
• neuronové sítě (počítačové) * MeSH
• Publikační typ
• časopisecké články MeSH

Intramembrane serine proteases of the rhomboid family are widespread, and their gradually uncovered functions in different organisms already suggest medical relevance for infectious diseases and cancer. However, selective inhibitors that could serve as research tools for rhomboids, for validation of their disease relevance, or as templates for drug development are lacking. Here I summarize the current knowledge about rhomboid protease mechanism and specificity, overview the currently used inhibitors, and conclude by proposing avenues for future development of rhomboid protease inhibitors.

• Klíčová slova
• Disease, Inhibitor, Mechanism, Rhomboid protease, Substrate specificity,
• MeSH
• endopeptidasy chemie   metabolismus   MeSH
• inhibitory proteas chemie   MeSH
• lidé MeSH
• membránové proteiny antagonisté a inhibitory   chemie   MeSH
• substrátová specifita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• endopeptidasy MeSH
• inhibitory proteas MeSH
• membránové proteiny MeSH

Objective. This paper introduces a winning solution (team ISIBrno-AIMT) to the official round of PhysioNet Challenge 2021. The main goal of the challenge was a classification of ECG recordings into 26 multi-label pathological classes with a variable number of leads (e.g. 12, 6, 4, 3, 2). The main objective of this study is to verify whether the multi-head-attention mechanism influences the model performance.Approach. We introduced an ECG classification method based on the ResNet architecture with a multi-head attention mechanism for the official round of the challenge. However, empirical findings collected during model development suggested that the multi-head attention layer might not significantly impact the final classification performance. For this reason, during the follow-up round, we removed a multi-head attention layer to test the influence on model performance. Like the official round, the model is optimized using a mixture of loss functions, i.e. binary cross-entropy, custom challenge score loss function, and custom sparsity loss function. Probability thresholds for each classification class are estimated using the evolutionary optimization method. The final architecture consists of three submodels forming a majority voting classification ensemble.Main results. The modified model without the multi-head attention layer increased the overall challenge score to 0.59 compared to the 0.58 from the official round.Significance. Our findings from the follow-up submission support the fact that the multi-head attention layer in the proposed architecture does not significantly affect the classification performance.

• Klíčová slova
• ECG, PhysioNet challenge 2021, attention mechanism, classification, deep learning,
• MeSH
• algoritmy * MeSH
• elektrokardiografie * metody   MeSH
• entropie MeSH
• pravděpodobnost MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Stricter climate policies across the European Union are enhancing the phenomenon of free riding by nonacting countries, which translates into carbon leakage and loss of competitiveness. This paper investigates the trade, economic and environmental implications of the future implementation of a carbon border adjustment mechanism (CBAM) in Visegrád countries as EU member states. We exploit trade data to estimate price and income elasticities for emission-intensive trade-exposed (EITE) goods imported from non-EU trading partners to Visegrád countries. Based on these estimates, which are combined with the average carbon intensity of the EU's proposed list of EITE goods, we simulate the implications of six different configurations of restrictiveness of the CBAM imposed on imports from non-EU countries. We find that a high price elasticity and carbon intensity tend to significantly decrease import demand for EITE goods under the CBAM. Moreover, future CBAM implementation will yield a relatively small adverse impact on economic growth in Visegrád countries and a small decrease in total carbon emissions in non-EU countries.

• Klíčová slova
• Carbon border adjustment mechanism, Carbon leakage, Emission-intensive trade-exposed goods,
• Publikační typ
• časopisecké články MeSH

Multiwall WS2 nanotubes have been synthesized from W18O49 nanowhiskers in substantial amounts for more than a decade. The established growth model is based on the "surface-inward" mechanism, whereby the high-temperature reaction with H2S starts on the nanowhisker surface, and the oxide-to-sulfide conversion progresses inward until hollow-core multiwall WS2 nanotubes are obtained. In the present work, an upgraded in situ SEM μReactor with H2 and H2S sources has been conceived to study the growth mechanism in detail. A hitherto undescribed growth mechanism, named "receding oxide core", which complements the "surface-inward" model, is observed and kinetically evaluated. Initially, the nanowhisker is passivated by several WS2 layers via the surface-inward reaction. At this point, the diffusion of H2S through the already existing outer layers becomes exceedingly sluggish, and the surface-inward reaction is slowed down appreciably. Subsequently, the tungsten suboxide core is anisotropically volatilized within the core close to its tips. The oxide vapors within the core lead to its partial out-diffusion, partially forming a cavity that expands with reaction time. Additionally, the oxide vapors react with the internalized H2S gas, forming fresh WS2 layers in the cavity of the nascent nanotube. The rate of the receding oxide core mode increases with temperatures above 900 °C. The growth of nanotubes in the atmospheric pressure flow reactor is carried out as well, showing that the proposed growth model (receding oxide core) is also relevant under regular reaction parameters. The current study comprehensively explains the WS2 nanotube growth mechanism, combining the known model with contemporary insight.

• Klíčová slova
• WS2 nanotube, electron microscopy, ex situ, in situ, reaction mechanism, sulfidation,
• Publikační typ
• časopisecké články MeSH

Even though amyloid aggregates were discovered many years ago the mechanism of their formation is still a mystery. Because of their connection to many of untreatable neurodegenerative diseases the motivation for finding a common aggregation path is high. We report a new high heat induced fibrillization path of a model protein β-lactoglobulin (BLG) when incubated in glycine instead of water at pH 2. By combining atomic force microscopy (AFM), transmission emission microscopy (TEM), dynamic light scattering (DLS) and circular dichroism (CD) we predict that the basic building blocks of fibrils made in glycine are not peptides, but rather spheroid oligomers of different height that form by stacking of ring-like structures. Spheroid oligomers linearly align to form fibrils by opening up and combining. We suspect that glycine acts as an hydrolysation inhibitor which consequently promotes a different fibrillization path. By combining the known data on fibrillization in water with our experimental conclusions we come up with a new fibrillization scheme for BLG. We show that by changing the fibrillization conditions just by small changes in buffer composition can dramatically change the aggregation pathway and the effect of buffer shouldn't be neglected. Fibrils seen in our study are also gaining more and more attention because of their pore-like structure and a possible cytotoxic mechanism by forming pernicious ion-channels. By preparing them in a simple model system as BLG we opened a new way to study their formation.

• Klíčová slova
• Buffer specific effects, Fibrillization mechanism, Spheroid oligomers, β-lactoglobulin,
• MeSH
• amyloid * chemie   MeSH
• glycin farmakologie   MeSH
• laktoglobuliny * chemie   MeSH
• mikroskopie atomárních sil metody   MeSH
• voda MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amyloid * MeSH
• glycin MeSH
• laktoglobuliny * MeSH
• voda MeSH

Naphthoquinone is a heterocyclic moiety whose natural derivatives are present as bioactive compounds in many plants and have stimulated a resurgence of interest in the past decades due to their wide range of pharmacological activities. Naphthoquinone agents have dynamic pharmacophores and privileged sub-structures in the chemistry of medicine. They have received much interest in drug discovery as trypanocidal because naphthoquinone and their derivatives revealed massive significance potential against the trypanosomes. Among natural naphthoquinones, lapachol, β-lapachone and its α-isomer exhibited useful trypanocidal activities. Some naphthoquinones have already been used commercially as an antiparasitic agent. Several naphthoquinones with diverse structural motifs have been synthesized and evaluated mainly against Trypanosoma cruzi and some studies have also been reported against Trypanosoma brucei and Trypanosoma evansi. This review summarized various mechanisms of action of naphthoquinone like reductive activation of quinone by the production of the semiquinone, generation of reactive oxygen species and free radicals such as superoxide anion radical and H2O2, and oxidative stress in the parasite. The information assembled in this review will help to understand the mechanism behind the activity and may also be useful to find the bio-efficacy of naphthoquinone compounds upon substitution against trypanosomatids.

• Klíčová slova
• Mechanism of action., Naphthoquinone, Oxidative stress, Quinone reduction, Reactive oxygen species, Trypanosomatids,
• MeSH
• naftochinony * farmakologie   MeSH
• peroxid vodíku * MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• naftochinony * MeSH
• peroxid vodíku * MeSH

In this work, we investigate ethanol (EtOH)-sensing mechanisms of a ZnO nanorod (NRs)-based chemiresistor using a near-ambient-pressure X-ray photoelectron spectroscopy (NAP-XPS). First, the ZnO NRs-based sensor was constructed, showing good performance on interaction with 100 ppm of EtOH in the ambient air at 327 °C. Then, the same ZnO NRs film was investigated by NAP-XPS in the presence of 1 mbar oxygen, simulating the ambient air atmosphere and O2/EtOH mixture at the same temperature. The partial pressure of EtOH was 0.1 mbar, which corresponded to the partial pressure of 100 ppm of analytes in the ambient air. To better understand the EtOH-sensing mechanism, the NAP-XPS spectra were also studied on exposure to O2/EtOH/H2O and O2/MeCHO (MeCHO = acetaldehyde) mixtures. Our results revealed that the reaction of EtOH with chemisorbed oxygen on the surface of ZnO NRs follows the acetaldehyde pathway. It was also demonstrated that, during the sensing process, the surface becomes contaminated by different products of MeCHO decomposition, which decreases dc-sensor performance. However, the ac performance does not seem to be affected by this phenomenon.

• Klíčová slova
• ZnO nanorods, acetaldehyde pathway, carbon contamination, ethanol-sensing mechanism, near-ambient pressure XPS,
• Publikační typ
• časopisecké články MeSH

For the past decade, researchers have been trying to understand the mechanism of the thermal reduction of graphite oxide. Because deuterium is widely used as a marker in various organic reactions, we wondered if deuterium-labeled graphite oxide could be the key to fully understand this mechanism. Graphite oxides were prepared by the Hofmann, Hummers, Staudenmaier, and Brodie methods, and a deuterium-labeled analogue was synthesized by the Hofmann method. All graphite oxides were analyzed not only using the traditional techniques but also by gas chromatography-mass spectrometry (GC-MS) during exfoliation in hydrogen and nitrogen atmospheres. GC-MS enabled us to compare differences between the chemical compositions of the organic exfoliation products formed during the thermal reduction of these graphite oxides. Nuclear analytical methods (Rutherford backscattering spectroscopy, elastic recoil detection analysis) were used to calculate the concentrations of light elements, including the ratio of hydrogen to deuterium. Combining all of these results we were able to determine graphite oxide's thermal reduction mechanism. Carbon dioxide, carbon monoxide, and water are formed from the thermal reduction of graphite oxide. This process is also accompanied by various radical reactions that lead to the formation of a large amount of carcinogenic volatile organic compounds, and this will have major safety implications for the mass production of graphene.

• Klíčová slova
• exfoliation, graphene, graphite oxide, isotope labeling, mechanism,
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In laboratory experiments, many electrophilic cytotoxic agents induce cell death accompanied by reactive oxygen species (ROS) production and/or by glutathione (GSH) depletion. Not surprisingly, millimolar concentrations of N-acetylcysteine (NAC), which is used as a universal ROS scavenger and precursor of GSH biosynthesis, inhibit ROS production, restore GSH levels, and prevent cell death. The protective effect of NAC is generally used as corroborative evidence that cell death induced by a studied cytotoxic agent is mediated by an oxidative stress-related mechanism. However, any simple interpretation of the results of the protective effects of NAC may be misleading because it is unable to interact with superoxide (O2•-), the most important biologically relevant ROS, and is a very weak scavenger of H2O2. In addition, NAC is used in concentrations that are unnecessarily high to stimulate GSH synthesis. Unfortunately, the possibility that NAC as a nucleophile can directly interact with cytotoxic electrophiles to form non-cytotoxic NAC-electrophile adduct is rarely considered, although it is a well-known protective mechanism that is much more common than expected. Overall, apropos the possible mechanism of the cytoprotective effect of NAC in vitro, it is appropriate to investigate whether there is a direct interaction between NAC and the cytotoxic electrophile to form a non-cytotoxic NAC-electrophilic adduct(s).

• Klíčová slova
• N-acetylcysteine, N-acetylcysteine-electrophile adduct, electrophile, mechanism of protection, nucleophile,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH