Cyclization of 1-hydrazinyl-3,3-dimethyl-3,4-tetrahydro-5
H
-benzo
c
azepine with ethyl orthoformate gave 5,5-dimethyl-6,7-dihydro-5
H
benzo
c
-1,2,4-triazolo3,4-
a
azepine, and its reaction with ...acetic acid afforded 3,5,5-trimethyl-9,10-dimethoxy-6,7-dihydro-5
Н
-benzo
c
-1,2,4-triazolo3,4-
a
azepine. Nitrosation of 1-hydrazino-3,3-dimethyl-3,4-tetrahydro-5
H
-benzo
c
azepine led to the formation of substituted 6,7-dihydro-5
H
-benzo
c
tetrazolo5,1-
a
azepines.
Introduction: the article deals with maintaining the quality of teaching during curtailment of academic hours in curriculum. A university teacher should motivate students to use modern information ...technology training. The authors of the article describe the optimal didactic capabilities of modern information technologies to be used to improve the preparedness of a chemistry graduate. The aim of the article is to highlight the problem of finding the optimal didactic capabilities of modern information technologies used for improving the system of training specialists in the field of chemistry and to discuss the results of current studies in this direction. Materials and Methods: the authors summarised the relevant literature and results of the research and teaching experience. The main theoretical methods of research are modeling and designing the process of incorporating modern information technologies into the teaching of chemistry in the university. Theoretical methods are supplemented by empirical methods, such as observation, survey, testing, experimental work and methodological analysis. Results: the article reveals the main components of the system of teaching chemistry at higher educational establishments using information technology, identifies necessary electronic didactic materials for their implementation, training and monitoring programmes, presents their approbation in real conditions of pedagogical activity and the results obtained. The article presents the results of a pedagogical experiment, which proves the effectiveness of using these approaches in the training of chemists. Discussion and Conclusions: the electronic educational materials, manuals and recommendations developed by the authors can be used in teachinga future chemistry graduate in a number of chemical disciplines and can serve as a basis for the development of information, communication and instrumental provision in other chemical subjects. The main directions for further research are as follows: to create and to test electronic textbooks and teaching aids, to develop variants of using Internet technologies in teaching chemistry.
Atrial fibrillation (AF) commonly associates with atrial dilatation by poorly understood mechanisms. We hypothesized that elevation of intra-atrial pressure elicits high-frequency and ...spatio-temporally organized left atrial (LA) sources emanating from the superior pulmonary veins.
We used a stretch-related AF model in the sheep heart to induce stable episodes of AF (>40 minutes) in 9 animals. Video movies of the LA free wall (LAFW) and LA superior pulmonary vein junction (JPV) were obtained by using di-4-ANEPPS. Electrograms from the right atrium were recorded. At intra-atrial pressures >10 cm H2O, the maximum dominant frequency (DFMax) was significantly higher in the JPV than in the LAFW (12.0+/-0.2 and 10.5+/-0.2 Hz, respectively mean+/-SEM; P<0.001). Below 10 cm H2O, DFMax was similar in the JPV and LAFW (10.8+/-0.3 versus 10.2+/-0.3 Hz; P=0.6); DFMax in both JPV and LAFW was significantly higher than in the right atrium (7.8+/-0.3 Hz; P<0.001). Analysis of excitation direction in JPV showed positive correlation between intra-atrial pressure and the number of waves emanating from the left superior pulmonary vein (r=0.79, P=0.02) but not from the LAFW (r=0.54, P=0.09). The number of spatio-temporally periodic waves in the JPV correlated with pressure (r=0.92, P=0.002). In 3 cases, JPV rotors were identified with a cycle length equal to 1/DFMax.
We demonstrate for the first time that an increase in intra-atrial pressure increases the rate and organization of waves emanating from the superior pulmonary veins underlying stretch-related AF.
High-frequency fractionated electrograms recorded during atrial fibrillation (AF) in the posterior left atrium (PLA) and elsewhere are being used as target sites for catheter ablation. We tested the ...hypothesis that highly periodic electric waves emerging from AF sources at or near the PLA give rise to the most fractionated activity in adjacent locations.
Sustained AF was induced in 8 isolated sheep hearts (0.5 micromol/L acetylcholine). Endocardial videoimaging (DI-4-ANEPPS) and electric mapping of the PLA enabled spatial characterization of dominant frequencies (DFs) and a regularity index (ratio of DF to total power). Regularity index showed that fractionation was lowest within the area with the maximal DF (DFmax domain; 0.19+/-0.02) and highest within a band of &3 mm (0.16+/-0.02; P=0.047) at boundaries with lower-frequency domains. The numbers of spatiotemporal periodic episodes (25.9+/-2.3) and rotors per experiment (1.9+/-0.7) were also highest within the DFmax domain. Most commonly, breakthrough waves at the PLA traveled toward the rest of the atria (76.8+/-8.1% outward versus 23.2+/-8.1% inward; P<0.01). In both experiments and simulations with an atrial ionic model, fractionation at DFmax boundaries was associated with increased beat-to-beat variability of conduction velocity and directionality with wavebreak formation.
During stable AF, the PLA harbors regular, fast, and highly organized activity; the outer limit of the DFmax domain is the area where the most propagation pattern variability and fractionated activity occur. These new concepts introduce a new perspective in the clinical use of high-frequency fractionated electrograms to localize sources of AF precisely at the PLA and elsewhere.
The "stress" kinases cAMP-dependent protein kinase (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII), phosphorylate the Na
channel Nav1.5 subunit to regulate its function. However, ...how the channel regulation translates to ventricular conduction is poorly understood. We hypothesized that the stress kinases positively and differentially regulate conduction in the right (RV) and the left (LV) ventricles. We applied the CaMKII blocker KN93 (2.75 μM), PKA blocker H89 (10 μM), and broad-acting phosphatase blocker calyculin (30 nM) in rabbit hearts paced at a cycle length (CL) of 150-8,000 ms. We used optical mapping to determine the distribution of local conduction delays (inverse of conduction velocity). Control hearts exhibited constant and uniform conduction at all tested CLs. Calyculin (15-min perfusion) accelerated conduction, with greater effect in the RV (by 15.3%) than in the LV (by 4.1%;
< 0.05). In contrast, both KN93 and H89 slowed down conduction in a chamber-, time-, and CL-dependent manner, with the strongest effect in the RV outflow tract (RVOT). Combined KN93 and H89 synergistically promoted conduction slowing in the RV (KN93: 24.7%; H89: 29.9%; and KN93 + H89: 114.2%;
= 0.0016) but not the LV. The progressive depression of RV conduction led to conduction block and reentrant arrhythmias. Protein expression levels of both the CaMKII-δ isoform and the PKA catalytic subunit were higher in the RVOT than in the apical LV (
< 0.05). Thus normal RV conduction requires a proper balance between kinase and phosphatase activity. Dysregulation of this balance due to pharmacological interventions or disease is potentially proarrhythmic.
We show that uniform ventricular conduction requires a precise physiological balance of the activities of calcium/calmodulin-dependent protein kinase II (CaMKII), PKA, and phosphatases, which involves region-specific expression of CaMKII and PKA. Inhibiting CaMKII and/or PKA activity elicits nonuniform conduction depression, with the right ventricle becoming vulnerable to the development of conduction disturbances and ventricular fibrillation/ventricular tachycardia.
Organismal functional strategies form a continuum from slow- to fast-growing organisms, in response to common drivers such as resource availability and disturbance. However, whether there is ...synchronisation of these strategies at the entire community level is unclear. Here, we combine trait data for >2800 above- and belowground taxa from 14 trophic guilds spanning a disturbance and resource availability gradient in German grasslands. The results indicate that most guilds consistently respond to these drivers through both direct and trophically mediated effects, resulting in a 'slow-fast' axis at the level of the entire community. Using 15 indicators of carbon and nutrient fluxes, biomass production and decomposition, we also show that fast trait communities are associated with faster rates of ecosystem functioning. These findings demonstrate that 'slow' and 'fast' strategies can be manifested at the level of whole communities, opening new avenues of ecosystem-level functional classification.
1. Along with the global decline of species richness goes a loss of ecological traits. Associated biotic homogenization of animal communities and narrowing of trait diversity threaten ecosystem ...functioning and human well-being. High management intensity is regarded as an important ecological filter, eliminating species that lack suitable adaptations. Below-ground arthropods are assumed to be less sensitive to such effects than above-ground arthropods. 2. Here, we compared the impact of management intensity between (grassland vs. forest) and within land-use types (local management intensity) on the trait diversity and composition in below- and above-ground arthropod communities. 3. We used data on 722 arthropod species living above-ground (Auchenorrhyncha and Heteroptera), primarily in soil (Chilopoda and Oribatida) or at the interface (Araneae and Carabidae). 4. Our results show that trait diversity of arthropod communities is not primarily reduced by intense local land use, but is rather affected by differences between land-use types. Communities of Auchenorrhyncha and Chilopoda had significantly lower trait diversity in grassland habitats as compared to forests. Carabidae showed the opposite pattern with higher trait diversity in grasslands. Grasslands had a lower proportion of large Auchenorrhyncha and Carabidae individuals, whereas Chilopoda and Heteroptera individuals were larger in grasslands. Body size decreased with land-use intensity across taxa, but only in grasslands. The proportion of individuals with low mobility declined with land-use intensity in Araneae and Auchenorrhyncha, but increased in Chilopoda and grassland Heteroptera. The proportion of carnivorous individuals increased with land-use intensity in Heteroptera in forests and in Oribatida and Carabidae in grasslands. 5. Our results suggest that gradients in management intensity across land-use types will not generally reduce trait diversity in multiple taxa, but will exert strong trait filtering within individual taxa. The observed patterns for trait filtering in individual taxa are not related to major classifications into above- and below-ground species. Instead, ecologically different taxa resembled each other in their trait diversity and compositional responses to land-use differences. These previously undescribed patterns offer an opportunity to develop management strategies for the conservation of trait diversity across taxonomic groups in permanent grassland and forest habitats.
Styryl voltage-sensitive dyes (e.g., di-4-ANEPPS) have been used successfully for optical mapping in cardiac cells and tissues. However, their utility for probing electrical activity deep inside the ...myocardial wall and in blood-perfused myocardium has been limited because of light scattering and high absorption by endogenous chromophores and hemoglobin at blue-green excitation wavelengths.
The purpose of this study was to characterize two new styryl dyes--di-4-ANBDQPQ (JPW-6003) and di-4-ANBDQBS (JPW-6033)--optimized for blood-perfused tissue and intramural optical mapping.
Voltage-dependent spectra were recorded in a model lipid bilayer. Optical mapping experiments were conducted in four species (mouse, rat, guinea pig, and pig). Hearts were Langendorff perfused using Tyrode's solution and blood (pig). Dyes were loaded via bolus injection into perfusate. Transillumination experiments were conducted in isolated coronary-perfused pig right ventricular wall preparations.
The optimal excitation wavelength in cardiac tissues (650 nm) was >70 nm beyond the absorption maximum of hemoglobin. Voltage sensitivity of both dyes was approximately 10% to 20%. Signal decay half-life due to dye internalization was 80 to 210 minutes, which is 5 to 7 times slower than for di-4-ANEPPS. In transillumination mode, DeltaF/F was as high as 20%. In blood-perfused tissues, DeltaF/F reached 5.5% (1.8 times higher than for di-4-ANEPPS).
We have synthesized and characterized two new near-infrared dyes with excitation/emission wavelengths shifted >100 nm to the red. They provide both high voltage sensitivity and 5 to 7 times slower internalization rate compared to conventional dyes. The dyes are optimized for deeper tissue probing and optical mapping of blood-perfused tissue, but they also can be used for conventional applications.
The mechanisms by which Na-channel blocking antiarrhythmic drugs terminate atrial fibrillation (AF) remain unclear. Classical “leading-circle” theory suggests that Na-channel blockade should, if ...anything, promote re-entry. We used an ionically-based mathematical model of vagotonic AF to evaluate the effects of applying pure Na-current (INa) inhibition during sustained arrhythmia. Under control conditions, AF was maintained by 1 or 2 dominant spiral waves, with fibrillatory propagation at critical levels of action potential duration (APD) dispersion. INa inhibition terminated AF increasingly with increasing block, terminating all AF at 65% block. During 1:1 conduction, INa inhibition reduced APD (by 13% at 4 Hz and 60% block), conduction velocity (by 37%), and re-entry wavelength (by 24%). During AF, INa inhibition increased the size of primary rotors and reduced re-entry rate (eg, dominant frequency decreased by 33% at 60% INa inhibition) while decreasing generation of secondary wavelets by wavebreak. Three mechanisms contributed to INa block–induced AF termination in the model(1) enlargement of the center of rotation beyond the capacity of the computational substrate; (2) decreased anchoring to functional obstacles, increasing meander and extinction at boundaries; and (3) reduction in the number of secondary wavelets that could provide new primary rotors. Optical mapping in isolated sheep hearts confirmed that tetrodotoxin dose-dependently terminates AF while producing effects qualitatively like those of INa inhibition in the mathematical model. We conclude that pure INa inhibition terminates AF, producing activation changes consistent with previous clinical and experimental observations. These results provide insights into previously enigmatic mechanisms of class I antiarrhythmic drug-induced AF termination. The full text of this article is available online at http://circres.ahajournals.org
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