Using 3D Hidden Markov Models that explicitly represent spatial coordinates to model and compare protein structures

BACKGROUND: Hidden Markov Models (HMMs) have proven very useful in computational biology for such applications as sequence pattern matching, gene-finding, and structure prediction. Thus far, however, they have been confined to representing 1D sequence (or the aspects of structure that could be represented by character strings). RESULTS: We develop an HMM formalism that explicitly uses 3D coordinates in its match states. The match states are modeled by 3D Gaussian distributions centered on the mean coordinate position of each alpha carbon in a large structural alignment. The transition probabilities depend on the spread of the neighboring match states and on the number of gaps found in the structural alignment. We also develop methods for aligning query structures against 3D HMMs and scoring the result probabilistically. For 1D HMMs these tasks are accomplished by the Viterbi and forward algorithms. However, these will not work in unmodified form for the 3D problem, due to non-local quality of structural alignment, so we develop extensions of these algorithms for the 3D case. Several applications of 3D HMMs for protein structure classification are reported. A good separation of scores for different fold families suggests that the described construct is quite useful for protein structure analysis. CONCLUSION: We have created a rigorous 3D HMM representation for protein structures and implemented a complete set of routines for building 3D HMMs in C and Perl. The code is freely available from , and at this site we also have a simple prototype server to demonstrate the features of the described approach

Physical Processes and Plasma Parameters in a Radio-Frequency Hybrid Plasma System for Thin-Film Production with Ion Assistance

The results of the study of the plasma reactor on the combined magnetron discharge and radio-frequency (RF) inductive discharge located in the external magnetic field are presented. Magnetron discharge provides the generation of atoms and ions of the target materials, while the flow of accelerated ions used for the ion assistance is provided by the RF inductive discharge located in an external magnetic field. Approaching the region of resonant absorption of RF power by optimizing the magnitude and configuration of the external magnetic field makes it possible to obtain a uniform within 10% radial distribution of the ion current across the diameter of 150 mm. When the RF power supply power is 1000 W, the ion current density on the substrate can be adjusted in the range of 0.1–3 mA/cm2. The use of ion assisting results in a fundamental change in the structure and properties of functional coatings, deposited using a magnetron

Public Administration in the Sphere of Tourism and Yachting

An article is devoted to the problem of human potential development through the life quality increasing. Nowadays several critical public weal sources are deprived of state care and protection. The subsequent problems are analysed on the base of yachting and nautical tourism. Different approaches to obtain an executive power support from the ministries - emergency situation, transport and tourism (culture) are considered. The possible future merger between yachting and tourism industry is evaluated in light of modern trends

SAHA Enhances Synaptic Function and Plasticity In Vitro but Has Limited Brain Availability In Vivo and Does Not Impact Cognition

Suberoylanilide hydroxamic acid (SAHA) is an inhibitor of histone deacetylases (HDACs) used for the treatment of cutaneous T cell lymphoma (CTCL) and under consideration for other indications. In vivo studies suggest reducing HDAC function can enhance synaptic function and memory, raising the possibility that SAHA treatment could have neurological benefits. We first examined the impacts of SAHA on synaptic function in vitro using rat organotypic hippocampal brain slices. Following several days of SAHA treatment, basal excitatory but not inhibitory synaptic function was enhanced. Presynaptic release probability and intrinsic neuronal excitability were unaffected suggesting SAHA treatment selectively enhanced postsynaptic excitatory function. In addition, long-term potentiation (LTP) of excitatory synapses was augmented, while long-term depression (LTD) was impaired in SAHA treated slices. Despite the in vitro synaptic enhancements, in vivo SAHA treatment did not rescue memory deficits in the Tg2576 mouse model of Alzheimer’s disease (AD). Along with the lack of behavioral impact, pharmacokinetic analysis indicated poor brain availability of SAHA. Broader assessment of in vivo SAHA treatment using high-content phenotypic characterization of C57Bl6 mice failed to demonstrate significant behavioral effects of up to 150 mg/kg SAHA following either acute or chronic injections. Potentially explaining the low brain exposure and lack of behavioral impacts, SAHA was found to be a substrate of the blood brain barrier (BBB) efflux transporters Pgp and Bcrp1. Thus while our in vitro data show that HDAC inhibition can enhance excitatory synaptic strength and potentiation, our in vivo data suggests limited brain availability may contribute to the lack of behavioral impact of SAHA following peripheral delivery. These results do not predict CNS effects of SAHA during clinical use and also emphasize the importance of analyzing brain drug levels when interpreting preclinical behavioral pharmacology

Fermions in the harmonic potential and string theory

We explicitly derive collective field theory description for the system of fermions in the harmonic potential. This field theory appears to be a coupled system of free scalar and (modified) Liouville field. This theory should be considered as an exact bosonization of the system of non-relativistic fermions in the harmonic potential. Being surprisingly similar to the world-sheet formulation of c=1 string theory, this theory has quite different physical features and it is conjectured to give space-time description of the string theory, dual to the fermions in the harmonic potential. A vertex operator in this theory is shown to be a field theoretical representation of the local fermion operator, thus describing a D0 brane in the string language. Possible generalization of this result and its derivation for the case of c=1 string theory (fermions in the inverse harmonic potential) is discussed.Comment: 29 pages, 4 figures, LaTeX2e. v2 - minor correction

Phase Fluctuations and Pseudogap Phenomena

This article reviews the current status of precursor superconducting phase fluctuations as a possible mechanism for pseudogap formation in high-temperature superconductors. In particular we compare this approach which relies on the two-dimensional nature of the superconductivity to the often used $T$-matrix approach. Starting from simple pairing Hamiltonians we present a broad pedagogical introduction to the BCS-Bose crossover problem. The finite temperature extension of these models naturally leads to a discussion of the Berezinskii-Kosterlitz-Thouless superconducting transition and the related phase diagram including the effects of quantum phase fluctuations and impurities. We stress the differences between simple Bose-BCS crossover theories and the current approach where one can have a large pseudogap region even at high carrier density where the Fermi surface is well-defined. The Green's function and its associated spectral function, which explicitly show non-Fermi liquid behaviour, is constructed in the presence of vortices. Finally different mechanisms including quasi-particle-vortex and vortex-vortex interactions for the filling of the gap above $T_c$ are considered.Comment: 129 pages, Elsart, 28 EPS figures; Physics Reports, in press. Authors related information under "http://nonlin.bitp.kiev.ua/~sharapov/superconductivity.html

An ab-initio study of vibration dynamics in hydrogen-bonded compounds and intramolecular energy flow in the HDO molecule

Several new techniques were developed and applied to investigate various non-trivial aspects of vibrational motion. In particular, a novel strategy for accurate determination of vibrational energy levels in the presence of intramolecular hydrogen bonds was proposed. A small subset of convenient internal coordinates was chosen to represent a vibrational mode of interest, while the interdependence among all other coordinates was encoded in the g-matrix elements which appear in the kinetic energy operator. Individual g-matrix elements were modeled by series of shifted Gaussian functions, a newly proposed functional form that assured physically correct behavior for the entire domain of internal coordinates. The success in reproducing experimentally observed frequencies should be partly attributed to a new basis set of modified Hermite-type functions which has been introduced in this work and employed in all presented vibrational energy calculations. A novel functional representation for potential energy surfaces (PES) was also proposed in this work. The new representation, consisting of products of shifted Gaussians and shifted Morse functions, reproduces all local features near the bottom of the well and also possesses correct asympototic behavior. Determination of the functional parameters for the PES fits involved a simultaneous optimization of many linear and nonlinear parameters, and required a development of an efficient minimization routine. The new routine consisted of an iterative procedure, which treated sets of linear and nonlinear parameters separately and in successive order in each iteration. The above-mentioned set of developed tools was applied to study the intramolecular vibrational energy redistribution (IVR) in HDO molecule. The time-evolution of the O-H stretching local mode was studied by a time-propagation method based on matrix representation of the evolution operator. The energy transfer among the local modes was modeled by non-diagonal g-tensor terms in the kinetic energy operator and by three-dimensional potential energy operator. The results indicate that the O-H stretching local modes must be substantially long-lived within the chosen model. A new recursive programming technique combined with a very effective passing by reference methodology was developed and used in this study to implement the time-propagation routine. The introduced concept of a shared compound pointer in Fortran 90 automatically accounts for the changing sizes of all data structures, while working with only a single parameter, a pointer to a parent object

DIGITAL CONTROL OF AN UNDETERMINED OBJECT ON MEASUREMENTS OF FREQUENCE PARAMETERS

The new method of the finite-frequence identification of a discrete object has been suggested in the paper. Conditions for the problem solution of the exact digital control have been obtained. The algorithm of the lagging identification has been suggested. Software of the digital control on frequence parameters has been developed. The software-hardware realization of a frequence adaptive regulator has been represented. The paper results may find their field of application in the investigation, development and introduction of automatic control systemsAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio