The Feynman effective classical potential in the Schr\"odinger formulation

New physical insight into the correspondence between path integral concepts and the Schr\"odinger formulation is gained by the analysis of the effective classical potential, that is defined within the Feynman path integral formulation of statistical mechanics. This potential is related to the quasi-static response of the equilibrium system to an external force. These findings allow for a comprehensive formulation of dynamical approximations based on this potential.Comment: 10 pages, 4 figure

Complexes of Pd(II) and Pt(II) with 9-Aminoacridine: Reactions with DNA and Study of Their Antiproliferative Activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin

Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells

The main aim of this work was to develop novel targeted sterically stabilised pH-sensitive liposomes tailored to promote efficient intracellular delivery of therapeutic molecules into human T-leukaemia cells. Our results indicate that the targeting moiety (thiolated transferrin) was successfully coupled to the distal reactive maleimide terminus of poly(ethylene glycol)-phospholipid conjugates incorporated in the liposomal bilayer. Results from atomic force microscopy studies, performed to characterise vesicle surface topology, indicated that, to a certain extent, thiolated transferrin has the ability to associate in a non-specific manner with the lipid membrane of pegylated liposomes. This is an issue not commonly reported in the literature but which is crucial to demonstrate the targeting proof of principle. Nevertheless, fluorimetric studies together with confocal microscopy clearly demonstrate that liposomes bearing covalently coupled transferrin associate more extensively to human T-leukaemia cells in vitro than non-targeted liposomes. Cell mechanistic studies indicate that targeted liposomes bind specifically to transferrin receptors and are internalised via receptor-dependent endocytotic pathway. In addition, the biophysical features exhibited by the developed liposomes, namely their ability to promote pH-triggered cytoplasmic delivery of loaded material, make them promising delivery systems for in vivo targeting of therapeutic molecules to tumours.http://www.sciencedirect.com/science/article/B6T6C-4DVT9WH-1/1/5592c4a7248e7be29f239e55046f842

MoDeST: a compositional modeling formalism for hard and softly timed systems

This paper presents Modest (MOdeling and DEscription language for Stochastic Timed systems), a formalism that is aimed to support (i) the modular description of reactive system's behaviour while covering both (ii) functional and (iii) nonfunctional system aspects such as timing and quality-of-service constraints in a single specification. The language contains features such as simple and structured data types, structuring mechanisms like parallel composition and abstraction, means to control the granularity of assignments, exception handling, and non-deterministic and random branching and timing. Modest can be viewed as an overarching notation for a wide spectrum of models, ranging from labeled transition systems, to timed automata (and probabilistic variants thereof) as well as prominent stochastic processes such as (generalized semi-)Markov chains and decision processes. The paper describes the design rationales and details of the syntax and semantics

Single-channel transmission in gold one-atom contacts and chains

We induce superconductivity by proximity effect in thin layers of gold and study the number of conduction channels which contribute to the current in one-atom contacts and atomic wires. The atomic contacts and wires are fabricated with a Scanning Tunneling Microscope. The set of transmission probabilities of the conduction channels is obtained from the analysis of the $I(V)$ characteristic curve which is highly non-linear due to multiple Andreev reflections. In agreement with theoretical calculations we find that there is only one channel which is almost completely open.Comment: 4 pages, 2 figures. To be published in Phys. Rev. B, Rapid Communications (2003

Evolution of Robustness to Noise and Mutation in Gene Expression Dynamics

Phenotype of biological systems needs to be robust against mutation in order to sustain themselves between generations. On the other hand, phenotype of an individual also needs to be robust against fluctuations of both internal and external origins that are encountered during growth and development. Is there a relationship between these two types of robustness, one during a single generation and the other during evolution? Could stochasticity in gene expression have any relevance to the evolution of these robustness? Robustness can be defined by the sharpness of the distribution of phenotype; the variance of phenotype distribution due to genetic variation gives a measure of `genetic robustness' while that of isogenic individuals gives a measure of `developmental robustness'. Through simulations of a simple stochastic gene expression network that undergoes mutation and selection, we show that in order for the network to acquire both types of robustness, the phenotypic variance induced by mutations must be smaller than that observed in an isogenic population. As the latter originates from noise in gene expression, this signifies that the genetic robustness evolves only when the noise strength in gene expression is larger than some threshold. In such a case, the two variances decrease throughout the evolutionary time course, indicating increase in robustness. The results reveal how noise that cells encounter during growth and development shapes networks' robustness to stochasticity in gene expression, which in turn shapes networks' robustness to mutation. The condition for evolution of robustness as well as relationship between genetic and developmental robustness is derived through the variance of phenotypic fluctuations, which are measurable experimentally.Comment: 25 page

Chemical composition, nutritional value, and biological evaluation of Tunisian okra pods (Abelmoschus esculentus L. moench)

The aim of this work was to perform an unprecedented in-depth study on the bioactive phytochemicals of Abelmoschus esculentus L. Moench Tunisian landrace (Marsaouia). For this purpose, its nutritional, aroma volatile, and phenolic profiles were characterized, and sundry biological activities were assessed in vitro. The approximate composition revealed that total dietary fiber as the most abundant macronutrient, mainly insoluble dietary fiber, followed by total carbohydrates and proteins. In addition, okra pods were rich in K, Ca, Mg, organic acids, tocopherols, and chlorophylls. Gas Chromatography-Electron Impact Mass Spectrometry (GC-EIMS) analysis showed that oxygenated monoterpenes, sesquiterpene hydrocarbons, and phenylpropanoids were the predominant essential volatile components in A. esculentus pods. A total of eight flavonols were detected by High-Performance Liquid Chromatography coupled to a DAD detector and mass spectrometry by electrospray ionization (HPLC-DAD-MS/ESI); with quercetin-3-O-glucoside being the majority phenolic component, followed by quercetin-O-pentosyl-hexoside and quercetin-dihexoside. This pioneering study, evidences that Tunisian okra display promising antioxidant and cytotoxic actions, in addition to relevant inhibitory effects against α-amylase and α-glucosidase enzymes, and interesting analgesic activity