Parameter Φ0 Research Articles

High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors

AbstractBacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication and represent important antibacterial drug targets. To be successful as drug candidates, newly synthesized compounds must possess optimal lipophilicity, which enables efficient delivery to the site of action. In this study, retention behavior of twenty-three previously synthesized dual DNA gyrase and topoisomerase IV inhibitors was tested in RP-HPLC system, consisting of C8 column and acetonitrile/phosphate buffer (pH 5.5 and pH 7.4) mobile phase. logD was calculated at both pH values and the best correlation with logD was obtained for retention parameter φ0, indicating that this RP-HPLC system could be used as an alternative to the shake-flask determination of lipophilicity. Subsequent QSRR analysis revealed that intrinsic lipophilicity (logP) and molecular weight (bcutm13) have a positive, while solubility (bcutp3) has a negative influence on this retention parameter.

Quantum entropy of BMPV black holes and the topological M-theory conjecture

We present a formula for the quantum entropy of supersymmetric five-dimensional spinning black holes in M-theory compactified on CY3, i.e., BMPV black holes. We use supersymmetric localization in the framework of off-shell five dimensional N = 2 supergravity coupled to I = 1, . , NV + 1 off-shell vector multiplets. The theory is governed at two-derivative level by the symmetric tensor {mathcal{C}}_{IJK} (the intersection numbers of the Calabi-Yau) and at four-derivative level by the gauge-gravitational Chern-Simons coupling cI (the second Chern class of the Calabi-Yau). The quantum entropy is an NV +2-dimensional integral parameterised by one real parameter φI for each vector multiplet and an additional parameter φ0 for the gravity multiplet. The integrand consists of an action governed completely by {mathcal{C}}_{IJK} and cI, and a one-loop determinant. Consistency with the on-shell logarithmic corrections to the entropy, the symmetries of the very special geometry of the moduli space, and an assumption of analyticity constrains the one-loop determinant up to a scale-independent function g(φ0). For g = 1 our result agrees completely with the topological M-theory conjecture of Dijkgraaf, Gukov, Neitzke, and Vafa for static black holes at two derivative level, and provides a natural extension to higher derivative corrections. For rotating BMPV black holes, our result differs from the DGNV conjecture at the level of the first quantum corrections.

Study of the magnetization work of RPV steel in dependence on neutron irradiation

The reactor pressure vessel (RPV) steel exposed to neutron radiation during operation of nuclear power plant has to suffer the neutron irradiation degradation. For monitoring the radiation damage, especially using non-destructive evaluation methods, the magnetization work W of RPV steel subjected to different neutron radiation fluences Φ has been calculated from magnetization curves. It was found out that the W increases exponentially in relation to Φ in dpa, i.e., W = A + K[exp(Φ/Φ0) − 1]. In this equation, the item A denotes the magnetization work of the non-irradiated RPV steel, the parameter Φ0 is the eigenvalue of the neutron radiation fluence, and the parameter K reflects the sensitivity of the magnetization work to the neutron radiation. The magnetization work W, which can be calculated precisely from the magnetization curves without doing the demagnetizing correction, is highly sensitive to the radiation fluence Φ. So that, the neutron radiation fluence Φ in dpa can be quantitatively determined by measuring the magnetization curves of RPV steels.

Teicoplanin-Modified HPLC Column as a Source of Experimental Parameters for Prediction of the Anticonvulsant Activity of 1,2,4-Triazole-3-Thiones by the Regression Models.

The cell membrane is a complex system that consists of lipids, proteins, polysaccharides, and amphiphilic phospholipids. It plays an important role in ADME processes that are responsible for the final pharmaceutical effects of xenobiotics (bioavailability, activity). To study drug-membrane interaction at the molecular level, several high-performance liquid chromatography (HPLC) membrane model systems have been proposed which are mimicking mainly its lipid character. The aim of this work was to study interactions of new synthesized antiepileptic compounds of 4-alkyl-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives with Chirobiotic column containing glycoprotein ligand attached to the silica matrix. The affinity of the analytes to immobilized glycoprotein ligand was examined chromatographically in reversed-phase mode. The thermodynamics of interactions between bioactive compounds and teicoplanin was studied in terms of the van’t Hoff linear relationship ln k vs. 1/T in the range of 5–45 °C. Change in enthalpy (ΔH°), change in entropy (ΔS°) and change in Gibbs free energy (ΔG°) were estimated utilizing graphical extrapolation and interpolation methods. The density functional theory (DFT) approach and docking simulations were used to get the molecular interpretation and prove the obtained experimental results. Cross-correlations of chromatographic and thermodynamic parameters with non-empirical topological and quantum chemical indices suggest that the polarizability of analytes appears to be responsible for the interactions of the tested molecules with teicoplanin and, ultimately, their retention on the column. Experimental and theoretical parameters were subjected to statistical analysis using regression models. Partial least squares (PLS) regression model showed the usefulness of the experimentally measured parameter φ0 (MeOH) to discriminate between anticonvulsant active and inactive 1,2,4-triazole-3-thione derivatives. Obtained results point out the usefulness of interaction of potential anticonvulsants with glycoprotein class of compounds to anticipate their activity.

The Generalized Pomeron Functional Equation

This paper investigates the linear functional equation with constant coefficients φt=κφλt+ft, where both κ>0 and 1>λ>0 are constants, f is a given continuous function on ℝ, and φ:ℝ⟶ℝ is unknown. We present all continuous solutions of this functional equation. We show that (i) if κ>1, then the equation has infinite many continuous solutions, which depends on arbitrary functions; (ii) if 0<κ<1, then the equation has a unique continuous solution; and (iii) if κ=1, then the equation has a continuous solution depending on a single parameter φ0 under a suitable condition on f.

Dependence of the anticancer activity of 1,3‐oxazole derivatives on the donor/acceptor nature of his substitues

AbstractA series of new 1,3‐oxazole derivatives, containing in position 5 both donor and acceptor substituents were synthesized. These substances were considered as potentially active anticancer pharmacophores in the human tumor cell line panel derived from nine cancer types, including lung, colon, melanoma, renal, ovarian, brain, leukemia, breast, and prostate. Primary in vitro one‐dose anticancer screening was shown that compounds with acceptor substituents (such as –C(O)OMe, –CN) in the position 5 inhibit the growth of most cell lines, and compounds with donor substituents (such as –NHR, −SR) in the position 5 do not practically inhibit the growth of cancer cell lines. It can be assumed that the pharmacological activity of 1,3‐oxazole derivatives depends on donor/acceptor nature of the substituents in position 5. It was proposed to evaluate the donor/acceptor ability of 1,3‐oxazole derivatives using the special parameter φ0, which takes into account the relative position of the boundary levels (HOMO end LUMO). The quantum‐chemical modeling was performed; the special parameter φ0 for 1,3‐oxazole derivatives correlates with the experimental results. Quantum‐chemical calculations of the special parameter φ0 allow modeling the pharmacological activity of 1,3‐oxazole derivatives by introducing donor or acceptor substituents at position 2 or 5. This work may be useful for chemists to develop a target synthesis of potential biologically active compounds.

Development and Validation of Liquid Chromatography-Based Methods to Assess the Lipophilicity of Cytotoxic Platinum(IV) Complexes

Lipophilicity is a crucial parameter for drug discovery, usually determined by the logarithmic partition coefficient (Log P) between octanol and water. However, the available detection methods have restricted the widespread use of the partition coefficient in inorganic medicinal chemistry, and recent investigations have shifted towards chromatographic lipophilicity parameters, frequently without a conversion to derive Log P. As high-performance liquid chromatography (HPLC) instruments are readily available to research groups, a HPLC-based method is presented and validated to derive the partition coefficient of a set of 19 structurally diverse and cytotoxic platinum(IV) complexes exhibiting a dynamic range of at least four orders of magnitude. The chromatographic lipophilicity parameters φ0 and Log kw were experimentally determined for the same set of compounds, and a correlation was obtained that allows interconversion between the two lipophilicity scales, which was applied to an additional set of 34 platinum(IV) drug candidates. Thereby, a φ0 = 58 corresponds to Log P = 0. The same approaches were successfully evaluated to determine the distribution coefficient (Log D) of five ionisable platinum(IV) compounds to sample pH-dependent effects on the lipophilicity. This study provides straight-forward HPLC-based methods to determine the lipophilicity of cytotoxic platinum(IV) complexes in the form of Log P and φ0 that can be interconverted and easily expanded to other metal-based compound classes.

Areas and sizes of cascades in dissipative one-dimensional sandpile model

A prototypical self-organized sandpile mode is studied on a one-dimensional (1D) chain with periodic boundary conditions. A dissipation mechanism in which every grain being transferred between nodes has a probability ϵ to be taken out is needed, as the system has no boundary nodes for grains to fall off – a feature reminiscent of complex networks. Detailed numerical analysis revealed distributions of cascade areas D(a) and cascade sizes D(s) that are intrinsically different from other 1D sandpile models with an open end. Analyzing cascading processes on a chain, independent-site approximations to D(a) and D(s) are developed. The approximated distributions are given in terms of a single parameter ϕ0, which is the fraction of empty nodes when the system is stable. The approximations are shown to capture the key features of the distributions. The distribution of cascade sizes D(s) is shown to exhibit large fluctuations that cannot be suppressed by averaging over different realizations. Our approximation provides a physically transparent explanation of the intrinsic large fluctuations in terms of the number of ways that a cascade can proceed for achieving a certain size. To close the approximations, a semi-empirical formula for the parameter ϕ0 as a function of the dissipation probability ϵ is found. Our work thus reports non-trivial results on a seemingly simple model and sheds light on analyzing cascading processes in other complex networks with no boundary nodes.

Testing DARKexp against energy and density distributions of Millennium-II halos

We test the DARKexp model for relaxed, self-gravitating, collisionless systems against equilibrium dark matter halos from the Millennium-II simulation. While limited tests of DARKexp against simulations and observations have been carried out elsewhere, this is the first time the testing is done with a large sample of simulated halos spanning a factor of ∼ 50 in mass, and using independent fits to density and energy distributions. We show that DARKexp, a one shape parameter family, provides very good fits to the shapes of density profiles, ρ(r), and differential energy distributions, N(E), of individual simulated halos. The best fit shape parameter ϕ0 obtained from the two types of fits are correlated, though with scatter. Our most important conclusions come from ρ(r) and N(E) that have been averaged over many halos. These show that the bulk of the deviations between DARKexp and individual Millennium-II halos come from halo-to-halo fluctuations, likely driven by substructure, and other density perturbations. The average ρ(r) and N(E) are quite smooth and follow DARKexp very closely. The only deviation that remains after averaging is small, and located at most bound energies for N(E) and smallest radii for ρ(r). Since the deviation is confined to 3–4 smoothing lengths, and is larger for low mass halos, it is likely due to numerical resolution effects.

Parameter sensitivity and inversion analysis of a concrete faced rock-fill dam based on HS-BPNN algorithm

Considering the complex nonlinear relationship between the material parameters of a concrete faced rock-fill dam (CFRD) and its displacements, the harmony search (HS) algorithm is used to optimize the back propagation neural network (BPNN), and the HS-BPNN algorithm is formed and applied for the inversion analysis of the parameters of rock-fill materials. The sensitivity of the parameters in the Duncan and Chang’s E-B model is analyzed using the orthogonal test design. The case study shows that the parameters φ0, K, Rf, and Kb are sensitive to the deformation of the rock-fill dam and the inversion analysis for these parameters is performed by the HS-BPNN algorithm. Compared with the traditional BPNN, the HS-BPNN algorithm exhibits the advantages of high convergence precision, fast convergence rate, and strong stability.

Probing hybrid modified gravity by stellar motion around Galactic Center

We consider possible signatures for the so called hybrid gravity within the Galactic Central Parsec. This modified theory of gravity consists of a superposition of the metric Einstein–Hilbert Lagrangian with an f(R) term constructed à la Palatiniand can be easily reduced to an equivalent scalar–tensor theory. Such an approach is introduced in order to cure the shortcomings related to f(R) gravity, in general formulated either in metric or in metric-affine frameworks. Hybrid gravity allows to disentangle the further gravitational degrees of freedom with respect to those of standard General Relativity. The present analysis is based on the S2 star orbital precession around the massive compact dark object at the Galactic Center where the simulated orbits in hybrid modified gravity are compared with astronomical observations. These simulations result with constraints on the range of hybrid gravity interaction parameter ϕ0, showing that in the case of S2 star it is between −0.0009 and −0.0002. At the same time, we are also able to obtain the constraints on the effective mass parameter mϕ, and found that it is between −0.0034 and −0.0025 AU−1 for S2 star. Furthermore, the hybrid gravity potential induces precession of S2 star orbit in the same direction as General Relativity. In previous papers, we considered other types of extended gravities, like metric power law f(R)∝Rn gravity, inducing Yukawa and Sanders-like gravitational potentials, but it seems that hybrid gravity is the best among these models to explain different gravitational phenomena at different astronomical scales.

Conditions for tidal bore formation in convergent alluvial estuaries

Over the last decade there has been an increasing interest in tidal bore dynamics. However most studies have been focused on small-scale bore processes. The present paper describes the first quantitative study, at the estuary scale, of the conditions for tidal bore formation in convergent alluvial estuaries. When freshwater discharge and large-scale spatial variations of the estuary water depth can be neglected, tide propagation in such estuaries is controlled by three main dimensionless parameters: the nonlinearity parameter ε0, the convergence ratio δ0 and the friction parameter ϕ0. In this paper we explore this dimensionless parameter space, in terms of tidal bore occurrence, from a database of 21 estuaries (8 tidal-bore estuaries and 13 non tidal-bore estuaries). The field data point out that tidal bores occur for convergence ratios close to the critical convergence δc. A new proposed definition of the friction parameter highlights a clear separation on the parameter plane (ϕ0,ε0) between tidal-bore estuaries and non tidal-bore estuaries. More specifically, we have established that tidal bores occur in convergent estuaries when the nonlinearity parameter is greater than a critical value, εc, which is an increasing function of the friction parameter ϕ0. This result has been confirmed by numerical simulations of the two-dimensional Saint Venant equations. The real-estuary observations and the numerical simulations also show that, contrary to what is generally assumed, tide amplification is not a necessary condition for tidal bore formation. The effect of freshwater discharge on tidal bore occurrence has been analyzed from the database acquired during three long-term campaigns carried out on the Gironde/Garonne estuary. We have shown that in the upper estuary the tidal bore intensity is mainly governed by the local dimensionless tide amplitude ε. The bore intensity is an increasing function of ε and this relationship does not depend on freshwater discharge. However, freshwater discharge damps the tidal wave during its propagation and thus reduces ε and consequently limits the tidal bore development in the estuary. To take into account this process in the tidal-bore scaling analysis, it is necessary to introduce a fourth external parameter, the dimensionless river discharge Q0.

Experimental Measurements of Ingestion Through Turbine Rim Seals—Part II: Rotationally Induced Ingress

Part I of this two-part paper presented experimental results for externally-induced (EI) ingress, where the ingestion of hot gas through the rim seal into the wheel-space of a gas turbine is controlled by the circumferential variation of pressure in the external annulus. In Part II, experimental results are presented for rotationally-induced (RI) ingress, where the ingestion is controlled by the pressure generated by the rotating fluid in the wheel-space. Although EI ingress is the common form of ingestion through turbine rim seals, RI ingress or combined ingress (where EI and RI ingress are both significant) is particularly important for double seals, where the pressure asymmetries are attenuated in the annular space between the inner and outer seals. In this paper, the sealing effectiveness was determined from concentration measurements, and the variation of effectiveness with sealing flow rate was compared with theoretical curves for RI ingress obtained from an orifice model. Using a nondimensional sealing parameter Φ0 the data could be collapsed onto a single curve, and the theoretical variation of effectiveness with Φ0 was in very good agreement with the data for a wide range of flow rates and rotational speeds. It was shown that the sealing flow required to prevent RI ingress was much less than that needed for EI ingress, and it was also shown that the effectiveness of a radial-clearance seal is significantly better than that for an axial-clearance seal for both EI and RI ingress.

Step-shape angular spin distribution in layered systems by 57Fe Mössbauer spectroscopy: A general treatment

In the so-called ‘step-shape’ angular spin distribution model for layered systems, the non-collinear directions of the atomic magnetic moments are confined to the film plane and form a homogeneous fan spanning inside an (in-plane) angular interval Δφ centered at an angle φ0. A general approach for deriving the two parameters φ0 and Δφ via 57Fe Mössbauer spectroscopy measurements is discussed. The analysis extends our previously reported treatment, which assumed that the angular aperture Δφ develops symmetrically versus a fixed direction φ0 (e.g., the in-plane easy axis of magnetization) oriented either along or perpendicular to the in-plane projection of the Mössbauer γ-ray direction. The proposed approach is also applicable for those cases when not only the spin aperture Δφ is changing but also the aperture center φ0 is rotating under the influence of different external parameters, such as applied field, temperature, stress, etc. The method is suitable for applications to nanoscale layered heterostructures with in-plane uniaxial or unidirectional magnetic anisotropy. The method is applied to experimental data obtained on a 2-nm thick defected Fe layer with in-plane magnetic texture.

Public opinion evolution model with the variable topology structure based on scale free network

Based on scale free network, the public opinion evolution model is constructed, in which the public opinion changes with topology (the relationship and the influence between the individual). The model features that the network structure constantly changes in the process of evolution with evolution parameter φ0. It is found that the evolution of the public opinion not only is controlled by the topological structure, but also induces the change of the topological structure: the network structure is no longer the initial scale-free network,but it has a Poisson distribution. With the time evolution in system, there is obvious convergence effect of the public opinions. The dozens of opinions in initial state evolve with time, but most of them perish and only a few of them can survive and develop for a long time. The evolution trend is coincident with that of the public opinions, views and beliefs in society.

Saturation fluorimetry of complex organic compounds with a high local concentration of fluorophores (by the example of phytoplankton)

Saturation of fluorescence of complex organic compounds with a high local concentration of fluorescing molecules (fluorophores), when singlet—singlet annihilation makes a noticeable contribution to saturation, is considered. The fluorescence saturation curve is obtained analytically for the case of a rectangular temporal and spatial distribution of photons in a laser pulse. It is shown that the fluorescence saturation curve depends on the parameter Φ0, which is proportional to the concentration of fluorescing molecules, and on the parameters A, B, and α describing the influence of singlet—singlet annihilation, bleaching of an optically thin layer, and nonstationarity of excitation, respectively. The fluorescence saturation curves are studied experimentally for compounds with a high local concentration of fluorescing molecules such as molecules of a monoculture of diatomic alga Thalassiosira weissflogii. The experimental fluorescence saturation curves are well described by the obtained analytic expression. The values of the parameter Φ0, proportional to the concentration of chlorophyll a, and the parameter A (for the first time) are obtained from the alga fluorescence saturation curves.

Kinetische Untersuchungen zum Reaktionsmechanismus der Carnitindehydrogenase aus Pseudomonas aeruginosa

Carnitine dehydrogenase from Pseudomonas aeruginosa catalyzes the reversible reduction of 3-dehydrocarnitine to carnitine. The enzyme is specific for NADH and 3-dehydrocarnitne in the reduction and for NAD+ and l-carnitine in the oxidation reaction. Carnitine dehydrogenase differs from other dehydrogenases in from other dehydrogenases in the polar structure of both of its substrates, carnitine and 3-dehydrocarnitine. So differences in the enzyme-substrate binding and in the reaction mechanism might be expected. The enzyme used in our experiments was of a high specific activity (600 μmoles NAD+/min/mg protein), purified by means of ammonium sulphate fractionation, gel filtration and DEAE cellulose and hydroxyl apatite chromatography. The dependence of initial velocity on the substrate concentration was investigated in the oxidation and reduction reacations. The results are presented in the form of double reciprocal plots. The slopes and intercepts of these primary plots were replotted versus reciprocal substrate concentrations yielding secondary plots. Slopes and intercepts of these secondary plots correspond to the kinetic parameters ϕ0, ϕ1, ϕ2, ϕ12 (reduction reaction) and ϕ0, ϕ′1, ϕ′2, and ϕ′12, (oxidation reaction). The quotients obtained from these values agree with the conditions for a special case of ordered Bi Bi mechanism, the so-called Theorell-Chance mechanism. The limiting Michaelis constants for both substrates in the reduction and oxidation reactions, the dissociation constants for the binary complexes of the enzyme with NADH or NAD+, and the equilibrium constants of the overall reacrtion are presented. The product inhibition patterns also correspond to those predicted by the Theorell-Chance mechanism.

Perturbation Method for Boundary S-Matrix in 2D Quantum Field Theory

We develop a perturbation theory for evaluating the boundary S-matrix in 2D quantum field theory. We apply this approach to calculate the one-loop boundary S-matrix for the elementary particle of the sine–Gordon model with a boundary interaction. Our perturbative result agrees with the exact expression of the S-matrix conjectured by Goshal; it also allows us to derive the perturbative relation between the parameter ϑ in the S-matrix and the free parameter M in the boundary action, in the particular case in which its other free parameter φ0 is zero.

Estimation of the RP-HPLC Lipophilicity Parameters Log K', and Log KW, A Comparison with the Hydrophobicity Index ϕ0 †

Chromatographic retention parameters k' and kW were determined by RP-HPLC for a set of standard non-congeneric compounds and the correlation with log Po/W established. Then, log Po/W was calculated for a series of antimicrobial hydrazides, as a test set. A comparison of the chromatographic parameters log k' and log KW with the hydrophobicity index ϕ0 were also made. It seems that for the study compounds, log KW describes the partitioning better than the parameter ϕ0. †Work presented at the International Symposium on Lipophilicity and Toxicology, Lausanne, Switzerland, 21–24 March, 1995.

Spectral distribution of backseattered electrons: Application to electron probe microanalysis

AbstractThe parameters ϕ0 and γ0 of the Gaussian model for the depth distribution of characteristic x‐ray production ϕ(ρz) were evaluated using an analytical expression for the energy distribution of backscatrered electrons. The expressions obtained were compared with those which do not take into account this distribution. A test of the usefulness of both models was performed for microanalysis corrections.