Differential pharmacologic properties of the two C75 enantiomers: (+)-C75 is a strong anorectic drug. (-)-C75 has antitumour activity

C75 is a synthetic compound described as having antitumoral properties. It produces hypophagia and weight loss in rodents, limiting its use in cancer therapy but identify- ing it as a potential anti-obesity drug. C75 is a fatty acid synthase (FAS) inhibitor and, through its coenzyme A (CoA) derivative, it acts as a carnitine palmitoyltransferase (CPT) 1 inhibitor. Racemic mixtures of C75 have been used in all the previous studies; however, the potential dif- ferent biological activities of C75 enantiomers have not been examined yet. To address this question we synthesized the two C75 enantiomers separately. Our results showed that ( )- C75 inhibits FAS activity in vitro and has a cytotoxic effect on tumor cell lines, without affecting food consumption. (+)-C75 inhibits CPT1 and its administration produces anorexia, suggesting that central inhibition of CPT1 is essential for the anorectic effect of C75. The differential activity of C75 enantiomers may lead to the development of potential new specific drugs for cancer and obesity.

Differential pharmacologic properties of the two C75 enantiomers: (+)-C75 is a strong anorectic drug. (-)-C75 has antitumour activity

C75 is a synthetic compound described as having antitumoral properties. It produces hypophagia and weight loss in rodents, limiting its use in cancer therapy but identify- ing it as a potential anti-obesity drug. C75 is a fatty acid synthase (FAS) inhibitor and, through its coenzyme A (CoA) derivative, it acts as a carnitine palmitoyltransferase (CPT) 1 inhibitor. Racemic mixtures of C75 have been used in all the previous studies; however, the potential dif- ferent biological activities of C75 enantiomers have not been examined yet. To address this question we synthesized the two C75 enantiomers separately. Our results showed that ( )- C75 inhibits FAS activity in vitro and has a cytotoxic effect on tumor cell lines, without affecting food consumption. (+)-C75 inhibits CPT1 and its administration produces anorexia, suggesting that central inhibition of CPT1 is essential for the anorectic effect of C75. The differential activity of C75 enantiomers may lead to the development of potential new specific drugs for cancer and obesity.

Elastic properties and secondary structure formation of single-stranded DNA at monovalent and divalent salt conditions

Single-stranded DNA (ssDNA) plays a major role in several biological processes. It is therefore of fundamental interest to understand how the elastic response and the formation of secondary structures are modulated by the interplay between base pairing and electrostatic interactions. Here we measure force-extension curves (FECs) of ssDNA molecules in optical tweezers set up over two orders of magnitude of monovalent and divalent salt conditions, and obtain its elastic parameters by fitting the FECs to semiflexible models of polymers. For both monovalent and divalent salts, we find that the electrostatic contribution to the persistence length is proportional to the Debye screening length, varying as the inverse of the square root of cation concentration. The intrinsic persistence length is equal to 0.7 nm for both types of salts, and the effectivity of divalent cations in screening electrostatic interactions appears to be 100-fold as compared with monovalent salt, in line with what has been recently reported for single-stranded RNA. Finally, we propose an analysis of the FECs using a model that accounts for the effective thickness of the filament at low salt condition and a simple phenomenological description that quantifies the formation of non-specific secondary structure at low forces.

Identification of neuronal network properties from the spectral analysis of calcium imaging signals in neuronal cultures

Neuronal networks in vitro are prominent systems to study the development of connections in living neuronal networks and the interplay between connectivity, activity and function. These cultured networks show a rich spontaneous activity that evolves concurrently with the connectivity of the underlying network. In this work we monitor the development of neuronal cultures, and record their activity using calcium fluorescence imaging. We use spectral analysis to characterize global dynamical and structural traits of the neuronal cultures. We first observe that the power spectrum can be used as a signature of the state of the network, for instance when inhibition is active or silent, as well as a measure of the network's connectivity strength. Second, the power spectrum identifies prominent developmental changes in the network such as GABAA switch. And third, the analysis of the spatial distribution of the spectral density, in experiments with a controlled disintegration of the network through CNQX, an AMPA-glutamate receptor antagonist in excitatory neurons, reveals the existence of communities of strongly connected, highly active neurons that display synchronous oscillations. Our work illustrates the interest of spectral analysis for the study of in vitro networks, and its potential use as a network-state indicator, for instance to compare healthy and diseased neuronal networks.

Influence of the pseudopotential on the properties of liquid rubidium at 315 K

The influence of the pseudopotential on both the structure and the self-diffusion of liquid rubidium at the melting point has been investigated by means of molecular-dynamics calculations. The model potential considered has been computed from the pseudopotential of Ashcroft, the dielectric function of Geldart and Vosko, and a Born-Mayer term. Four different values for the core radius which enters as input in the pseudopotential have been considered. In this way we have been able to observe and interpret the effect of this contribution on the properties of the liquid.

Wigner higher-order spectra: definition, properties, computation and application to transient signal analysis

The Wigner higher order moment spectra (WHOS)are defined as extensions of the Wigner-Ville distribution (WD)to higher order moment spectra domains. A general class oftime-frequency higher order moment spectra is also defined interms of arbitrary higher order moments of the signal as generalizations of the Cohen’s general class of time-frequency representations. The properties of the general class of time-frequency higher order moment spectra can be related to theproperties of WHOS which are, in fact, extensions of the properties of the WD. Discrete time and frequency Wigner higherorder moment spectra (DTF-WHOS) distributions are introduced for signal processing applications and are shown to beimplemented with two FFT-based algorithms. One applicationis presented where the Wigner bispectrum (WB), which is aWHOS in the third-order moment domain, is utilized for thedetection of transient signals embedded in noise. The WB iscompared with the WD in terms of simulation examples andanalysis of real sonar data. It is shown that better detectionschemes can be derived, in low signal-to-noise ratio, when theWB is applied.

Analysis of thermal properties of phase change materials (PCM) using differential scanning calorimeter (DSC)

Commercially available PCM RT 20, RT 27, SP 22, A17 and SP 25 A8. Were analyzed using dynamic and step method of heat flux DSC. The results of the dinamic and step method were compared with commercial valures. It was found that RT 20 & RT 27 showed good conforming of results with commercial values while SP 22 A17 & SP 25 A8 did not show conformity.

Psychometric properties of the French version of the Zuckerman-Kuhlman Personality Questionnaire

Este estudio instrumental fue diseñado para investigar las propiedades psicométricas de la versión francesa y replicabilidad transcultural del Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) en sus factores y facetas. El ZKPQ es un instrumento destinado a evaluar los cinco factores básicos del Alternative Five-Factor Model (AFFM). Los participantes fueron 843 suizos francófonos, principalmente estudiantes universitarios. Obtenidos los factores estos mostraron una fiabilidad entre 0,73 y 0,87, y sus facetas entre 0,57 y 0,77. Las diferencias entre géneros son similares a las informadas en la muestra americana. Las mujeres alcanzaron puntuaciones superiores en N-Anx, y puntuaciones más bajas en ImpSS y Act. El resultado de los análisis factoriales exploratorios respaldó la estructura de cinco factores y sus correspondientes facetas. Las correlaciones entre las escalas sostienen que los cinco factores básicos del AFFM son ortogonales. Los coeficientes de congruencia muestran la elevada eplicabilidad transcultural de los factores y sus facetas. Se puso a prueba el ajuste del modelo en sus factores y facetas mediante análisis factorial confirmatorio. Los resultados indican que la versión en lengua francesa del ZKPQ es un instrumento fiable y válido y posee buena replicabilidad transcultural.

A logic programming framework for possibilistic argumentation: formalization and logical properties

In the last decade defeasible argumentation frameworks have evolved to become a sound setting to formalize commonsense, qualitative reasoning. The logic programming paradigm has shown to be particularly useful for developing different argument-based frameworks on the basis of different variants of logic programming which incorporate defeasible rules. Most of such frameworks, however, are unable to deal with explicit uncertainty, nor with vague knowledge, as defeasibility is directly encoded in the object language. This paper presents Possibilistic Logic Programming (P-DeLP), a new logic programming language which combines features from argumentation theory and logic programming, incorporating as well the treatment of possibilistic uncertainty. Such features are formalized on the basis of PGL, a possibilistic logic based on G¨odel fuzzy logic. One of the applications of P-DeLP is providing an intelligent agent with non-monotonic, argumentative inference capabilities. In this paper we also provide a better understanding of such capabilities by defining two non-monotonic operators which model the expansion of a given program P by adding new weighed facts associated with argument conclusions and warranted literals, respectively. Different logical properties for the proposed operators are studied

Properties of amorphous silicon thin films grown in square wave modulated silane rf discharges.

Hydrogenated amorphous silicon (a‐Si:H) thin films have been obtained from pure SiH4 rf discharges by using the square wave modulation (SQWM) method. Film properties have been studied by means of spectroellipsometry, thermal desorption spectrometry, photothermal deflection spectroscopy and electrical conductivity measurements, as a function of the modulation frequency of the rf power amplitude (0.2-4000 Hz). The films deposited at frequencies about 1 kHz show the best structural and optoelectronic characteristics. Based upon the experimental results, a qualitative model is presented, which points up the importance of plasma negative ions in the deposition of a‐Si:H from SQWM rf discharges through their influence on powder particle formation.

Psychometric properties and dimensional structure of the Spanish version of the Coping Responses Inventory - Adult Form

One of the goals of psychological assessment focuses on the adaptation of its instruments to different populations. The objective of this study is to establish the psychometric properties and dimensional structure of the Spanish version of the Coping Responses Inventory- Adult Form (CRI-Adult, Moos, 1993). The following criteria were analyzed: a) descriptive statistics; b) internal consistency reliability (Cronbach"s alpha, and intercorrelations between scales); c) test-retest reliability (4-week interval); d) dimensionality of CRI-Adult (exploratory factor analysis); e) construct validity (confirmatory factor analysis); f) convergent criterion validity (correlations between CRI-Adult and Coping Strategies Indicator, CSI, Amirkhan, 1990), and g) predictive criterion validity (correlations between CRI-Adult, and SCL-90-R, Derogatis, 1983). The results, obtained with 800 adults from Barcelona and surrounding area (334 men and 466 women, aged between 18 to 76 years) indicate that the Spanish version of CRIAdult has satisfactory psychometric properties that allow using this test with guarantee.

The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants

Surfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants which differ in the nature of their counterion were studied. Their capacity to disrupt the cell membrane was examined under a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model for endosomal membranes. The surfactants showed pH-sensitive hemolytic activity and improved kinetics at the endosomal pH range. Low concentrations resulted in negligible hemolysis at physiological pH and high membrane lytic activity at pH 5.4, which is in the range characteristic of late endosomes. With increasing concentration, the surfactants showed an enhanced capacity to lyse cell membranes, and also caused significant membrane disruption at physiological pH. This observation indicates that, at high concentrations, surfactant behavior is independent of pH. The mechanism of surfactant-mediated membrane destabilization was addressed, and scanning electron microscopy studies were also performed to evaluate the effects of the compounds on erythrocyte morphology as a function of pH. The in vitro cytotoxicity of the surfactants was assessed by MTT and NRU assays with the 3T3 cell line. The influence of different types of counterion on hemolytic activity and the potential applications of these surfactants in drug delivery are discussed. The possibility of using pH-sensitive surfactants for endosome disruption could hold great promise for intracellular drug delivery systems in future therapeutic applications.

Correlation of the EPR properties of perchlorotriphenylmethyl radical and their efficiency as DNP polarizers

Water soluble perchlorinated trityl (PTM) radicals were found to be effective 95 GHz DNP (dynamic nuclear polarization) polarizers in ex situ (dissolution) 13C DNP (Gabellieri et al., Angew Chem., Int. Ed. 2010, 49, 3360). The degree of the nuclear polarization obtained was reported to be dependent on the position of the chlorine substituents on the trityl skeleton. In addition, on the basis of the DNP frequency sweeps it was suggested that the 13C NMR signal enhancement is mediated by the Cl nuclei. To understand the DNP mechanism of the PTM radicals we have explored the 95 GHz EPR characteristics of these radicals that are relevant to their performance as DNP polarizers. The EPR spectra of the radicals revealed axially symmetric g-tensors. A comparison of the spectra with the 13C DNP frequency sweeps showed that although the solid effect mechanism is operational the DNP frequency sweeps reveal some extra width suggesting that contributions from EPR forbidden transitions involving 35,37Cl nuclear flips are likely. This was substantiated experimentally by ELDOR (electron-electron double resonance) detected NMR measurements, which map the EPR forbidden transitions, and ELDOR experiments that follow the depolarization of the electron spin upon irradiation of the forbidden EPR transitions. DFT (density functional theory) calculations helped to assign the observed transitions and provided the relevant spin Hamiltonian parameters. These results show that the 35,37Cl hyperfine and nuclear quadrupolar interactions cause a considerable nuclear state mixing at 95 GHz thus facilitating the polarization of the Cl nuclei upon microwave irradiation. Overlap of Cl nuclear frequencies and the 13C Larmor frequency further facilitates the polarization of the 13C nuclei by spin diffusion. Calculation of the 13C DNP frequency sweep based on the Cl nuclear polarization showed that it does lead to an increase in the width of the spectra, improving the agreement with the experimental sweeps, thus supporting the existence of a new heteronuclear assisted DNP mechanism.

Nuclear surface properties in relativistic effective field theory

We perform Hartree calculations of symmetric and asymmetric semi-infinite nuclear matter in the framework of relativistic models based on effective hadronic field theories as recently proposed in the literature. In addition to the conventional cubic and quartic scalar self-interactions, the extended models incorporate a quartic vector self-interaction, scalar-vector non-linearities and tensor couplings of the vector mesons. We investigate the implications of these terms on nuclear surface properties such as the surface energy coefficient, surface thickness, surface stiffness coefficient, neutron skin thickness and the spin-orbit force.