Understanding the dielectric properties of liquid amides from a polarizable force field.

The role played by electronic polarization in the dielectric properties of liquid N-methyl acetamide (NMA) is examined using molecular dynamics simulations with a polarizable force field based on classical Drude oscillators. The model presented is the first force field shown to reproduce the anomalously large dielectric constant of liquid NMA. Details of the molecular polarizability are found to be important.

DFT study of B-like conformations of deoxydinucleoside monophosphates containing Gua and/or Cyt and their complexes with Na+ cation.

B-like minimum energy conformations of deoxydinucleoside monophosphate anions (dDMPs) containing Gua and/or Cyt and their Na+ complexes have been studied by the DFT PW91PW91/DZVP method. The optimized geometry of the dDMPs is in close agreement with experimental observations and the obtained minimum energy conformations are consistent with purine-purine, purine-pyrimidine, and pyrimidine-purine arrangements in crystals of B-DNA duplexes. All the studied systems are characterized by pyramidalization of the amino groups, which participate in the formation of unusual hydrogen bond between the carbonyl oxygen of the second base in the dGpdC, dCpdG dDMPs, and their Na+ complexes.

Collapse of magnetic moment drives the Mott transition in MnO.

The metal-insulator transition in correlated electron systems, where electron states transform from itinerant to localized, has been one of the central themes of condensed-matter physics for more than half a century. The persistence of this question has been a consequence both of the intricacy of the fundamental issues and the growing recognition of the complexities that arise in real materials, when strong repulsive interactions play the primary role. The initial concept of Mott was based on the relative importance of kinetic hopping (measured by the bandwidth) and onsite repulsion of electrons.

[The influences of geroprotectors on age-related changes of antioxidant system in rats liver under different light condition].

The influences of different light condition, melatonin and epithalon on liver antioxidant system in 6-, 12-, 18- and 24-month-old rats of both sexes were studied. The activities of antioxidant enzymes as well as concentration of tocopherol demonstrate high stability. The maximal number of significant changes in antioxidant system parameters was found under continuous light exposure.

Deficiency in Poly(ADP-ribose) Polymerase-1 (PARP-1) Accelerates Aging and Spontaneous Carcinogenesis in Mice.

Genetic and biochemical studies have shown that PARP-1 and poly(ADP-ribosyl)ation play an important role in DNA repair, genomic stability, cell death, inflammation, telomere maintenance, and suppressing tumorigenesis, suggesting that the homeostasis of poly(ADP-ribosyl)ation and PARP-1 may also play an important role in aging. Here we show that PARP-1(-/-) mice exhibit a reduction of life span and a significant increase of population aging rate. Analysis of noninvasive parameters, including body weight gain, body temperature, estrous function, behavior, and a number of biochemical indices suggests the acceleration of biological aging in PARP-1(-/-) mice.

[Lighting effect on spontaneous tumor development in female rats].

The investigation is concerned with effects of lighting--12hr light/12hr dark (standard), natural lighting in the Russian North-West, constant illumination and light deprivation--on life span and spontaneous tumor development in female LIO rats. Constant and North-West lighting involved premature aging, shorter mean (13.5 and 25%) and maximum life span (by 9 and 7 months, respectively) and a significant increase in spontaneous tumor development rate as compared with standard lighting.

NiO: correlated band structure of a charge-transfer insulator.

The band structure of the prototypical charge-transfer insulator NiO is computed by using a combination of an ab initio band structure method and the dynamical mean-field theory with a quantum Monte-Carlo impurity solver. Employing a Hamiltonian which includes both Ni d and O p orbitals we find excellent agreement with the energy bands determined from angle-resolved photoemission spectroscopy. This brings an important progress in a long-standing problem of solid-state theory.

[Gerontology in silico: the emergence of a new discipline].

In this paper the modern views concerning the place of mathematical and computer modeling of aging and aging related pathologies in the current state and in future developments of gerontology are discussed. The review of most perspective directions of research including analyses of demographic, molecular, cellular, and physiological mechanisms of aging, the roles of damage and reparation of DNA, cell proliferation and apoptosis, where application of mathematical modeling is promising is given. Special attention is paid to the results and perspectives of mathematical modeling in experimental gerontology including modeling of aging and longevity in laboratory animals (nematode worms, fruit flies, mice, rats) and humans.

[Age-dependent peculiarities of apoptotic marker proteins expression in the neuroendocrine system of Her2/neu transgenic mice].

The aim of our work was to study the expression of apoptotic signaling proteins and its relation to apoptosis level in neuroendocrine system of HER2/neu transgenic mice in aging. SHR mice served as controls. Bcl-2, Mcl-1, p53 and caspase-8 were demonstrated by immunohistochemistry in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei and relative content of apoptotic neurosecretory cells was determined.

[Specific features of spontaneous carcinogenesis and survival in female mice 129/Sv PARP-1+].

Spontaneous carcinogenesis and survival were compared in female mice 129/Sv PARP-1+ and PARP-1++ controls. Survival of all animals, including that of the last 10% of mice PARP-1+ (p<0.0002), was relatively lower.

[Melatonin suppresses benz(a)pyrene-induced carcinogenesis in mice].

Skin tumors were induced in 3 groups of out-bred mice SHR by painting with 0.05% solution of benz(a)pyrene and 0.2ml acetone beginning from the age of 3 months.

Modelling, prediction and adaptive adjustment of recruitment in multicentre trials.

This paper is focused on statistical modelling, prediction and adaptive adjustment of patient recruitment in multicentre clinical trials. We consider a recruitment model, where patients arrive at different centres according to Poisson processes, with recruitment rates viewed as a sample from a gamma distribution. A statistical analysis of completed studies is provided and properties of a few types of parameter estimators are investigated analytically and using simulation.

Methods of evaluating the effect of pharmacological drugs on aging and life span in mice.

The methodology of testing anti-aging drugs in laboratory mice is presented. It includes the selection of mouse strain, sex, age at start of treatment, housing conditions, design of the long-term study, some noninvasive methods of assessment, pathology examination, and statistical treatment of the results.

Doped Mott insulator as the origin of heavy-fermion behavior in LiV2O4.

We investigate the electronic structure of LiV2O4, for which heavy-fermion behavior has been observed in various experiments, by the combination of the local density approximation and dynamical mean field theory. To obtain results at zero temperature, we employ the projective quantum Monte Carlo method as an impurity solver. Our results show that the strongly correlated a 1g band is a lightly doped Mott insulator which, at low temperatures, shows a sharp (heavy) quasiparticle peak just above the Fermi level, which is consistent with recent photoemission experiments by Shimoyamada et al.

Additive and Classical Drude Polarizable Force Fields for Linear and Cyclic Ethers.

Empirical force field parameters consistent with the CHARMM additive and classical Drude based polarizable force fields are presented for linear and cyclic ethers. Initiation of the optimization process involved validation of the aliphatic parameters based on linear alkanes and cyclic alkanes. Results showed the transfer to cyclohexane to yield satisfactory agreement with target data; however, in the case of cyclopentane direct transfer of the Lennard-Jones parameters was not sufficient due to ring strain, requiring additional optimization of these parameters for this molecule.

Analysis of responses in migraine modelling using hidden Markov models.

Markov-type models have been used in the analysis of disease progression. Although standard errors of model parameters are usually estimated, available software often does not permit the construction of confidence intervals around predictions of the dependent or response variable. A method is presented to calculate means and confidence intervals of model-predicted responses in time governed by a non-homogeneous hidden Markov model in continuous time.

Implementation of the Madrid International Plan of Action on Aging: the role of research.

This article discusses the role of gerontological science in the implementation of the Madrid International Plan of Action on Aging. It contains the review of the Madrid Plan of Action (MPA), its aims, the process of its development and adoption, as well as basic problems arising in the process of its implementation. Also this article describes the contribution of Russian gerontological science to the implementation of the MPA.

Dose-dependent inhibitory effect of melatonin on carcinogenesis induced by benzo[a]pyrene in mice.

Three-month-old Swiss-derived SHR mice were subcutaneously injected with 2 mg of benzo[a]pyrene (BP) dissolved in 0.1 ml of olive oil. After the injections of the carcinogen two groups of mice were given melatonin with night drinking water at the doses of 2 mg/l or 20 mg/l and one group of mice was not treated with melatonin and served as a PB-control.

Biology of aging and cancer.

Background: The incidence of cancer increases with age in both humans and laboratory animals. A clear understanding of the causes of the age-related increase in cancer incidence is needed to develop a strategy for primary cancer prevention.

Methods: We summarized the data available in the literature and our own experience in hormonal metabolic shifts in organisms and disturbances at tissue and cellular levels observed in natural aging and in different types of carcinogenesis in vivo.

[Melatonin inhibits urethane-induced carcinogenesis tumors in murine lung].

Non-inbred SHR/u 3-month old mice were injected a single dose of urethane 1 g/kg, intraperitoneally. Beginning from day I after injection, they received melatonin 20 mg/l or 2 mg/l with drinking water at nighttime. After 28 days of the experiments, mice were sacrificed, lung adenomas counted and examined morphologically.

Premature ageing prevention: limitations and perspectives of pharmacological interventions.

A significant increase of the elderly in populations of developed countries is followed by increase morbidity and mortality from main age-related diseases--cardiovascular and neuro-degenerative, cancer, diabetes mellitus, declining in a resistance to infections. Obviously, the development of means of the prevention of the premature ageing and these diseases in humans are crucial at present. However, data on such type means rather scarce, contradictory and often not reliable from the points of view of the adequacy of the experiments to current scientific requirements, as well as the interpretation of the results and safety.

Validation of Linear Scaling Semiempirical LocalSCF Method.

The numerical accuracy of linear scaling semiempirical methods LocalSCF and MOZYME is analyzed in comparison to conventional matrix diagonalization with respect to a variety of molecular properties including conformational energy, dipole moment, atomic charges, and bond orders. Major semiempirical MNDO, AM1, PM3, and PM5 Hamiltonians were considered in the study. As the numerical tests demonstrate, both LocalSCF and MOZYME reasonably reproduce matrix diagonalization results with the deviations being below the accuracy of semiempirical methods.

Atomic Level Anisotropy in the Electrostatic Modeling of Lone Pairs for a Polarizable Force Field Based on the Classical Drude Oscillator.

Electron pairs in the valence shell of an atom that do not participate in the bonding of a molecule ("lone pairs") give rise to a concentrated electron density away from the atom center. To account for the asymmetry in the electron charge density that arises from lone pairs, an electrostatic model is developed that is parametrically anisotropic at the atomic level. The model uses virtual interaction sites with partial charges that are associated but not coincident with the nuclei.

Polarizable empirical force field for alkanes based on the classical Drude oscillator model.

Recent extensions of potential energy functions used in empirical force field calculations have involved the inclusion of electronic polarizability. To properly include this extension into a potential energy function it is necessary to systematically and rigorously optimize the associated parameters based on model compounds for which extensive experimental data are available. In the present work, optimization of parameters for alkanes in a polarizable empirical force field based on a classical Drude oscillator is presented.