Theoretical, spectroscopic, and chromatographic study of the structure and properties of para-substituted 5-benzylidenebarbituric acid derivatives with electron-donor and electron-acceptor substituents

5-Benziliden barbiturati pokazuju različitu biološku aktivnost koja je znatno uslovljena fizičkim, hemijskim i strukturnim osobinama jedinjenja, kao i zanimljive optičke osobine koje su posledica donor-akceptorskih interakcija u molekulu. Sintetisana je serija para-supstituisanih derivata 5-benzilidenbarbiturne kiseline kao potencijalnih push-pull elektronskih sistema sa elektron-donorskim i elektron-akceptorskim supstituentima. Proučavane su donor-akceptorske interakcije, kao i potencijalna elektron-donorska sposobnost barbiturne kiseline u sintetisanim jedinjenjima koja do sada nije potvrđena u literaturi. Elektronske interakcije u jedinjenjima u osnovnom stanju proučavane su LFER analizom NMR podataka, zajedno sa analizom optimizovanih geometrija i izračunatih elektronskih gustina. LSER analizom i TD-DFT proračunima proučavane su ekscitacije i pobuđena stanja. Rezultati "hole-electron" analize i izračunatih ICT deskriptora tokom ekscitacije pokazuju da je p-N(CH3)2 derivat najbolji kandidat za push-pull sistem. Utvrđeno je da barbiturna kiselina može biti slab elektron-donor kada je kuplovana sa jakim elektron-akceptorom. Primenom RP TLC metode određeni su hromatografski parametri lipofilnosti sintetisanih jedinjenja u metanolu, n-propanolu, acetonu i tetrahidrofuranu. Ispitana je zavisnost između hromatografskih parametara lipofilnosti (RМ0 i m), softverski dobijenih vrednosti logP kao standardne mere lipofilnosti, farmakokinetičkih i toksikoloških parametara primenom linearne regresije, klasterske analize i analize glavnih komponenata. Retenciono ponašanje ispitivanih jedinjenja znatno je uslovljeno prirodom supstituenata kao i njihovim elektronskim efektima. Rezultati potvrđuju da se hromatografski parametri, RМ0 i m mogu koristiti za opisivanje lipofilnosti ispitivanih jedinjenja.5-Benzylidenebarbiturates show different biological activities that are significantly influenced by the physical, chemical, and structural properties of the compound, as well as interesting optical properties resulting from donor-acceptor interaction in the molecules. A series of para-substituted 5-benzylidenebarbituric acid derivatives as potential push-pull electronic systems with electron-donor and electron-acceptor substituents was synthesized. The potential electron-donor abilities of barbituric acid, which are still not established in the literature, and donor-acceptor interactions in the synthesized compounds were investigated. The electronic interactions in the ground state were investigated by LFER analysis on 13C NMR data together with the analysis of optimized geometries and calculated electron densities. The electron excitations and the nature of excited state were studied by LSER analysis and TDDFT calculations. The results of the “hole-electron” analysis and calculated ICT descriptors during the excitation show that the p-N(CH3)2 derivative is the best candidate for the push-pull system. It has been found that barbituric acid can be a weak electron-donor when coupled with a strong electron-acceptor. The chromatographic lipophilicity parameters of the synthesized compounds were determined by the RP TLC in methanol, n-propanol, acetone, and tetrahydrofuran. The relationship between chromatographic lipophilicity parameters (RМ0 and m), theoretically calculated logP values as a standard measure of lipophilicity, pharmacokinetic and toxicological parameters was examined using the linear regression, cluster analysis, and principal component analysis. The retention behavior of the investigated compounds is significantly conditioned by the nature of the substituents as well as their electronic effects. The results confirm that the chromatographic parameters (RМ0 and m) can be used to describe the lipophilicity of the investigated compounds

Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs). In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment

Testing the Braneworld Theory with Identical Particles

Various attempts to go beyond the theory of General Relativity start from the assumption that spacetime is not a 4-dimensional but rather a higher-dimensional manifold. Among others, braneworld scenarios postulate that the spacetime we effectively observe is actually a 4-dimensional brane embedded in a higher-dimensional spacetime. In general, braneworld models predict a departure from the Newton gravity law in the nonrelativistic regime. Based on this fact, we propose an experimental test that uses a pair of gravitationally interacting identical particles to determine the validity of certain braneworld models and provide numerical results that should be compared with experimental data. In particular, we consider the Randal-Sundrum braneworld model and study two cases of 5-dimensional gravity theories: the Einstein-Hilbert gravity with the negative cosmological constant and the Einstein-Gauss-Bonnet (nearly-Chern-Simons) gravity.Comment: 6 pages, 6 figures, comments are welcom

Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs). In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.Centralni nervni sistem ima ograničen kapacitet za oporavak nakon povrede. Međutim, neonatalni mozak pokazuje veću sposobnost oporavka u odnosu na odrasle. Ove razlike zavise od lokalnih sredinskih faktora i stepena zrelosti aksona tokom izrastanja. U grupu molekula koji mogu da stimulišu ili inhibiraju rast aksona spada i heterogena klasa molekula označena kao hondroitin sulfatni proteoglikani (CSPG). U ovom radu ispitivanje profil ekspresije hondroitin-4 i hondroitin-6 sulfatnih proteoglikana nakonlezije leve senzomotorne kore neonatalnog i adultnog mozga pacova. Imunohistohemijska analiza pokazuje da u odnosu na normalni,nepovređeni korteks, lezija dovodi do povećanja ekspresije CSPG koji ima različiti obrazac promena u neonatalnom u odnosu na adultni mozak. Nakonlezije kod mladih, predominiraju tačkasta i membranski-vezana forma, dok kod odraslih lezija dovodi do nagomilavanja CSPG u ekstra ćelijskom matriksu. Prohodnija sredina u mozgu neonatalnih pacova koja je siromašnija CSPG, preduslov je boljeg procesa oporavka u odnosu na adulte, kod kojih se nakon povrede CSPG nagomilavaju oko mesta lezije.Projekat ministarstva br. 143005

SPEEDUP Code for Calculation of Transition Amplitudes via the Effective Action Approach

We present Path Integral Monte Carlo C code for calculation of quantum mechanical transition amplitudes for 1D models. The SPEEDUP C code is based on the use of higher-order short-time effective actions and implemented to the maximal order $p$=18 in the time of propagation (Monte Carlo time step), which substantially improves the convergence of discretized amplitudes to their exact continuum values. Symbolic derivation of higher-order effective actions is implemented in SPEEDUP Mathematica codes, using the recursive Schroedinger equation approach. In addition to the general 1D quantum theory, developed Mathematica codes are capable of calculating effective actions for specific models, for general 2D and 3D potentials, as well as for a general many-body theory in arbitrary number of spatial dimensions.Comment: 17 pages, 3 figures, uses cicp.cl

Seasonal changes in selected physical and physiological variables in male handball players

© 2018 Ljubomir Pavlović et al., published by Sciendo 2018. Literature search shows that there is a shortage of studies that have investigated the relationships between the physical conditioning markers monitored over the course of a season and the quantitative assessments of training and competition in elite handball players. Thus, the aim of our work was to follow changes in speed, strength, power and endurance of elite male handball players during an entire season. The study was performed within a group of 14 elite male senior handball players who were tested four times during season (T1, T2, T3, T4). The testing consisted of the following procedures: 1) measuring anthropometric characteristics (body height, body weight, body fat, % of fatty tissue), 2) measuring motorical (physical) capabilities (maximal muscle force and power, speed, explosive strength), 3) measuring physiological characteristics (anaerobic capacity, cardiorespiratory endurance). Explosive strength decreased at the end of season compared to the first part of season (T1 vs T4: p = 0.00, T2 vs T4: p = 0.00), as well as the total work done on modified Wingate test (T1 vs T4: p = 0.01). In contrast, blood lactate levels after the third (T1 vs T2: p = 0.00, T1 vs T3: p = 0.02; T1 vs T4:p = 0.00) and fourth (T1 vs T3: p = 0.02) stage of endurance test were the highest at the beginning of the season. Our results suggest that anaerobic capabilities of players were the ones mostly affected by long season and inadequate training program, while on the other side, aerobic capabilities improved by the end of season. Explanation for such results may be found in insufficient strength training or interference of endurance training with strength development

CHANGES IN SPEED, AGILITY AND BODY COMPOSITION OF TOP-RANKED FEMALE HANDBALL PLAYERS DURING THE PLAYING SEASON

Handball is a dynamic Olympic sport dominated by acyclic movements (sudden changes in direction, jumps, landings, contacts between the players, etc.) with speed and agility playing an important role in their successful realization. Our aim was to establish which changes occurred in the body composition, speed and agility of top-ranked female handball players during the playing season. The parameters for estimating body composition were: body mass, body mass index (BMI), the percentage of muscle and fat. The ability to achieve speed (in 5, 10 and 30m sprints) and agility (new envelope test without a ball, straight slalom run without a ball and Straight slalom run with a ball, zig-zag with and zig-zag without a ball) was estimated with the portable timing system. The differences between the initial and the final measurements were established with the Student’s t-test. The results obtained show that there were statistically significant changes and weaker results in almost all the tested variables. The only improvements were detected in the maximum speed in 30m sprint and the agility without a ball (new envelope test and slalom run without a ball). It is recommended that the training plan should be carefully devised (the activities of the high intensity load should be applied throughout the season) as well as the plan for proper sports nutrition (body mass should be reduced with simultaneous increase in the muscular mass component)

Modeling of wood chips gasification process in aspen plus with multiple validation approach

A thermochemical equilibrium model is formulated for wood chips downdraft gasification. Steady state ASPEN Plus simulator was utilized to evaluate producer gas composition and low heating value. Three cases are considered, due to mathematical model developed issues, and described in details. Experimental work was carried out within commercial small-scale CHP system where twelve beech wood samples were taken. Equivalence ratio is between 0.32 and 0.38 and air-fuel ratio ranges from 1.49 to 1.81, when gasifier capacity is optimal, at 250 kW. Mole fractions of CO2, H-2, CO, CH4 and N-2, in dry producer gas, are respectively, 16.06-1764, 1798-20.33, 13.71-1726, 1.65-289 and 43.21-48.36. Multiple validation approach was applied for model verification. The results are in reasonable agreement with different literature sources (experimental work and modeling) and in a great agreement with the modified equilibrium model developed in Engineering Equation Solver found in the literature. Result deviations are explained by two major facts: wood downdraft gasification experiments are to a certain extent different and the model parameters could not be adjusted enough to fully minimize differences between model results. Predicted low heating value of dry producer gas is between 467-5.61 MJ/Nm(3)

Modeling of wood chips gasification process in aspen plus with multiple validation approach

A thermochemical equilibrium model is formulated for wood chips downdraft gasification. Steady state ASPEN Plus simulator was utilized to evaluate producer gas composition and low heating value. Three cases are considered, due to mathematical model developed issues, and described in details. Experimental work was carried out within commercial small-scale CHP system where twelve beech wood samples were taken. Equivalence ratio is between 0.32 and 0.38 and air-fuel ratio ranges from 1.49 to 1.81, when gasifier capacity is optimal, at 250 kW. Mole fractions of CO2, H-2, CO, CH4 and N-2, in dry producer gas, are respectively, 16.06-1764, 1798-20.33, 13.71-1726, 1.65-289 and 43.21-48.36. Multiple validation approach was applied for model verification. The results are in reasonable agreement with different literature sources (experimental work and modeling) and in a great agreement with the modified equilibrium model developed in Engineering Equation Solver found in the literature. Result deviations are explained by two major facts: wood downdraft gasification experiments are to a certain extent different and the model parameters could not be adjusted enough to fully minimize differences between model results. Predicted low heating value of dry producer gas is between 467-5.61 MJ/Nm(3)

Combined treatment with ribavirin and tiazofurin attenuates response of glial cells in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), a human inflammatory and demyelinating disease. Microglia and astrocytes are glial cells of the central nervous system (CNS) that play a dual role in MS and EAE pathology. The aim of this study was to examine the effect of combined treatment with two nucleoside analogues, ribavirin and tiazofurin, on microglia and astrocytes in actively induced EAE. Therapeutic treatment with a combination of these two nucleoside analogues reduced disease severity, mononuclear cell infiltration and demyelination. The obtained histological results indicate that ribavirin and tiazofurin changed activated microglia into an inactive type and attenuated astrocyte reactivity at the end of the treatment period. Since reduction of reactive microgliosis and astrogliosis correlated with EAE suppression, the present study also suggests that the obtained beneficial effect of ribavirin and tiazofurin could be a consequence of their action inside as well as outside the CNS. [Acknowledgments. This work was supported by the Serbian Ministry of Education and Science, Project No: III41014.