•3D numerical CFD analysis for Trombe wall for a moderate continental climate.•3D model of passive house with Trombe wall is optimized.•For summer day, the glass is considered to be covered with PV ...stripes.•Analysis of energy savings potential is performed.
The paper deals with a comprehensive, three-dimensional numerical CFD analysis of temperature fields in Trombe wall and in the adjacent room for several days of a typical meteorological year (TMY) for a moderate continental climate. Construction of the Trombe wall is optimized, using different types of glassing on the outside of the wall. For summer day, the glass is considered to be covered with PV stripes during the daylight in order to prevent overheating. The central concrete core of the wall is covered with a layer of dark paint, on the outside, to improve absorptivity of the wall. The Trombe wall is oriented on south side of the house, and designed with openings with flaps in concrete core. Those openings are simulated in opened and closed positions. The U-values of the house envelope are considered according to passive house standards. Temperature fields in concrete core and in the room with Trombe wall are simulated, as well as velocity fields. According to these results, analysis of energy savings potential is performed.
Recently, we designed and synthesized a subnanomolar, reversible, dual-binding site acetylcholinesterase (AChE) inhibitor which consists of the tacrine and aroylacrylic acid phenylamide moieties, ...mutually linked by eight methylene units. To further investigate the process of the molecular recognition between the AChE and its inhibitor, we performed six unconstrained molecular dynamics (MD) simulations, where the compound in three possible protonation states was placed inside binding sites of two available AChE crystal structures. In all six MD trajectories, the ligand generally occupied similar space inside the AChE active site, but the pattern of the interactions between the ligand functional groups and the amino acid residues was significantly different and highly dependent upon the crystal structure used to generate initial systems for simulation. The greatest differences were observed between the trajectories obtained with different AChE crystal structures used as starting target conformations. In some trajectories, several unusual positions and dynamic behavior of the tacrine moiety were observed. Therefore, this study provides important structure-based data useful in further optimization of the reversible, dual binding AChE inhibitors, and also emphasizes the importance of the starting crystal structure used for dynamics as well as the protonation state of the reversible inhibitors.
Communicated by Ramaswamy H. Sarma
The systematically varying properties and generally coherent and predictable behavior of rare earth elements (REE) make them potential tracers for studying water/rock interaction and weathering ...processes. In this work, a compilation and analysis of REE data in mineral and thermal waters were performed, focusing on their content and distributions in different hydrogeological systems, to quantify the natural REE variability and to discuss the controlling factors of REE concentrations. Quantitative challenges presented by multiply censored data were addressed with nonparametric and multivariate statistical methods. Considering a regional character of the research the application of Q and R mode Hierarchical Cluster Analysis with spatial analysis was an important approach for meaningful interpretation of large data set. An efficient approach to analyze differences between obtained HCA groups (clusters) was using a plot of reference-normalized concentrations. The results showed that REE data along with anomalies of Ce and Eu and inter-element ratios were good indicators of the aquifer lithology (hydrogeological systems formed in granitoid and volcanic rocks of various age, two main types of hydrogeological basins, and carbonate aquifers). The important mechanisms controlling REE migration in water were hydrochemical conditions in aquifers. The significance of the applied statistical analyses was represented by defining specific hydrochemical fingerprints of identified hydrogeological systems with distinct geochemical characteristics where REE showed the necessity of understanding of complex geological and hydrogeological settings, geodynamic evolution, and hydrogeochemical processes in fluid flow systems.
Acetylcholinesterase (AChE) is an enzyme which terminates the cholinergic neurotransmission, by hydrolyzing acetylcholine at the nerve and nerve-muscle junctions. The reversible inhibition of AChE ...was suggested as the pre-treatment option of the intoxications caused by nerve agents. Based on our derived 3D-QSAR model for the reversible AChE inhibitors, we designed and synthesized three novel compounds 8-10, joining the tacrine and aroylacrylic acid phenylamide moieties, with a longer methylene chain to target two distinct, toplogically separated anionic areas on the AChE. The targeted compounds exerted low nanomolar to subnanomolar potency toward the E. eel and human AChE's as well as the human BChE and showed mixed inhibition type in kinetic studies. All compounds were able to slow down the irreversible inhibition of the human AChE by several nerve agents including tabun, soman and VX, with the estimated protective indices around 5, indicating a valuable level of protection. Putative noncovalent interactions of the selected ligand 10 with AChE active site gorge were finally explored by molecular dynamics simulation suggesting a formation of the salt bridge between the protonated linker amino group and the negatively charged Asp74 carboxylate side chain as a significant player for the successful molecular recognition in line with the design strategy. The designed compounds may represent a new class of promising leads for the development of more effective pre-treatment options.
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•Novel low nanomolar to subnanomolar inhibitors of hAChE have been synthesized.•Compounds protected AChE from irreversible inhibition by nerve agents.•The interactions of the compound 10 and AChE are investigated by MD simulations.
The paper presents an experimental analysis of the relationship between local thermal comfort and productivity loss in classrooms. The experimental investigation was performed in a real university ...classroom during the winter semester in city of Belgrade. Measurements were taken for four scenarios, with different indoor comfort conditions. Variations were made by setting the central heating system on/off, adding an additional heat source to provoke higher indoor temperatures, and measuring the radiant asymmetry impact. Innovative questionnaires were developed especially for the research, in order to investigate students? subjective feelings about local thermal comfort and indoor environmental quality. Local predicted mean vote and predicted percentage dissatisfied indices were calculated using data measured in situ. The results were compared to existing models recommended in literature and European and ASHRAE standards. Student productivity was evaluated using novel tests, designed to fit the purposes of the research. Surveys were conducted for 19 days under different thermal conditions, during lectures in a real classroom, using a sample of 240 productivity test results in total. Using the measured data, new correlations between the predicted mean vote, CO2, personal factor and productivity loss were developed. The research findings imply that local thermal comfort is an important factor that can impact productivity, but the impact of the personal factor is of tremendous importance, together with CO2 concentration in the classroom.
Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural ...variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme–substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide –NH– moiety of compounds and –OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE–compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding.
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•4-Aryl-4-oxo-2-aminylbutanamides were evaluated for anticholinesterase activity.•Twelve compounds exerted low micromolar inhibition potency toward AChE.•Three compounds inhibited BChE in low micromolar or submicromolar concentrations.•A hydrogen bond can be formed between compounds –NH– group and AChE Tyr 124 –OH.•The selectivity of compounds is governed by the nature of cycloalkylamino moiety.
•Novel Michael's adducts of aroylacrylic acid phenylamides have been synthesized.•The majority of compounds activated intrinsic apoptotic pathways.•Compounds showed moderate in vivo toxicity toward ...Artemia salina.•Compound 4 had superior antibacterial activity comparing to chloramphenicol.
In the present work, the α,β-double bond of the aroylacrylic acid phenylamides was suitably modified to optimize the toxicity–antiproliferative activity ratio of the resulting compounds 1–5. The phenylamides were modified by Michael's addition of suitably chosen piperidine-containing fragments: 1-amino-N-benzylpiperidine (a1), 4-benzylpiperidine (a2), and N,N-dimethyl-N-2-(1-piperazinyl)-ethylamine (a3). The compounds exerted micromolar activity toward three cancer cell lines, A549, LoVo, and Skov-3, causing apoptotic cell death. It was shown that the nature of the cyclic amine moiety at position C2 of the compounds is probably the primary determinant of anticancer activity toward tested cell lines and the acute toxicity toward brine shrimp (Artemia salina). The majority of compounds revealed the ability to vigorously induce mitochondrial superoxide anion generation in all treated cell lines, which together with cell cycle arrest at the S phase and activation of intrinsic caspase cascade, indicates the possibility that apoptosis was triggered due to irreparable chromosomal damage by acute oxidative stress. Two derivatives also exerted significant antibacterial activity with one order of magnitude higher potency than chloramphenicol in most of the investigated bacterial strains. Also, the drug-like properties for all compounds were estimated by available software tools.
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Regarding to the structure of final energy consumption in buildings and National Action Plans, the paper gives a short overview of energy consumption in buildings in Serbia, showing that the greatest ...potential for achieving savings lies in the implementation of measures which improve energy efficiency. Considering that over 60% of energy requirements for buildings is related to thermal energy, particular attention should be paid to the centralized heating systems, both during the design of a new system, and in the reconstruction of the existing one. Further discussed are the heat sources for the heating systems. The seasonal heat load duration curve for winter conditions in accordance to the Typical Meteorological Year for Belgrade is constructed and displayed. The analysis of the conventional system with a fossil fuel source, as well as the analysis of a hybrid heat source are conducted. The savings achieved in the primary energy, heating bills and CO emission reduction, which are attained by the use of a hybrid system, are shown in 2 comparison with the conventional systems. Collecting data on investment costs, as well as the prices of energy and fuels in Serbian market, enabled calculation of the payback period when replacing the conventional system by the new hybrid one.
nema
Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human tumor cell lines (HeLa, FemX, and K562) is reported. Compounds showed antiproliferative activity ...in one-digit micromolar to submicromolar concentrations. The most active derivatives toward all the cell lines tested bear alkyl substituents on the aroyl moiety of the molecules. Fourteen compounds showed tubulin assembly inhibition at concentrations <20 μM. The most potent inhibitor of tubulin assembly was unsubstituted compound 1, with IC50 = 2.9 μM. Compound 23 had an oral LD50in vivo of 45 mg/kg in mice. Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of the compounds. Nevertheless, they may be useful leads for the design of a new class of antitubulin agents.
•Different pre-treatments applied for S. montana supercritical extracts preparation.•GC/MS and GC/FID analysis of extracts and dominant compound-carvacrol was provided.•Ultrasound and high pressure ...pre-treatment increased content of carvacrol for 25%.•Extracts showed significant antioxidant activity, similar to vitamin C and BHT.
Main objective of this work was to investigate the influence of pre-treatments of Satureja montana herbal material on supercritical extraction process, in terms: influence on extraction yield, composition and antioxidant activity of extracts. Four different pretreatments were investigated: water pre-treatment, ethanol pre-treatment, ultrasound and high pressure pre-treatment. Extraction yields were in the range from 1.68 to 2.35g/100g. Pre-treatments with water and ethanol increase the yield of extraction for 25% and 17%, respectively. According to GC/MS results the main compound of obtained extracts was carvacrol. Analyses confirmed that carvacrol content in extracts can be significantly increased by application of pre-treatments. Ultrasound pre-treatment and high pressure pre-treatment yielded highest concentration of carvacrol in extracts (around 66%). Using these two pre-treatments of herbal material, concentration of carvacrol, in extracts obtained by supercritical carbon dioxide extraction, could be increased for around 25%. Antioxidant activity of all extract was very high and in the range of well-known antioxidants.
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