Conformation of the flexible bent helix of Leu1-zervamicin in crystal C and a possible gating action for ion passage

The membrane channel-forming polypeptide, Leu(1)-zervamicin, Ac-Leu-Ile-Gln-Iva-Ile(5)-Thr-Aib-Leu-Aib-Hyp(10) -Gln-Aib-Hyp-Aib-Pro(15)-Phol (Aib: alpha-aminoisobutyric acid; Iva: isovaline; Hyp: 4-hydroxyproline; Phol: phenylalininol) has been analyzed by x-ray diffraction in a third crystal form. Although the bent helix is quite similar to the conformations found in crystals A and B, the amount of bending is more severe with a bending angle approximate to 47 degrees, The water channel formed by the convex polar faces of neighboring helices is larger at the mouth than in crystals A and B, and the water sites have become disordered. The channel is interrupted in the middle by a hydrogen bond between the OH of Hyp(10) and the NH2 of the Gln(11) of a neighboring molecule. The side chain of Gln(11) is wrapped around the helix backbone in an unusual fashion in order that it can augment the polar side of the helix. In the present crystal C there appears to be an additional conformation for the Gln(11) side chain (with approximate to 20% occupancy) that opens the channel for possible ion passage. Structure parameters for C85H140N18O22.xH(2)O.C2H5OH are space group P2(1)2(1)2(1), a = 10.337 (2) Angstrom, b = 28.387 (7) Angstrom, c = 39.864 (11) Angstrom, Z = 4, agreement factor R = 12.99% for 3250 data observed > 3 sigma(F), resolution = 1.2 Angstrom. (C) 1994 John Wiley & Sons, Inc.

First passage probability during random vibration

The probability that a random process crosses an arbitrary level for the first time is expressed as a Gram—Charlier series, the leading term of which is the Poisson approximation. The coefficients of this series are related to the moments of the number of level crossings. The results are applicable to both stationary and non-stationary processes. Some numerical results are presented for the response process of a linear single-degree-of-freedom oscillator under Gaussian white noise excitation.

Mean first passage time approach to the problem of optimal barrier subdivision for Kramer's escape rate

We consider the effect of subdividing the potential barrier along the reaction coordinate on Kramer's escape rate for a model potential, Using the known supersymmetric potential approach, we show the existence of an optimal number of subdivisions that maximizes the rate, We cast the problem as a mean first passage time problem of a biased random walker and obtain equivalent results, We briefly summarize the results of our investigation on the increase in the escape rate by placing a blow-torch in the unstable part of one of the potential wells. (C) 1999 Elsevier Science B.V. All rights reserved.

First passage distributions for long memory processes

We study the distribution of first passage time for Levy type anomalous diffusion. A fractional Fokker-Planck equation framework is introduced.For the zero drift case, using fractional calculus an explicit analytic solution for the first passage time density function in terms of Fox or H-functions is given. The asymptotic behaviour of the density function is discussed. For the nonzero drift case, we obtain an expression for the Laplace transform of the first passage time density function, from which the mean first passage time and variance are derived.

Carboxyl terminal domain basic amino acids of mycobacterial topoisomerase I bind DNA to promote strand passage

Bacterial DNA topoisomerase I (topoI) carries out relaxation of negatively supercoiled DNA through a series of orchestrated steps, DNA binding, cleavage, strand passage and religation. The N-terminal domain (NTD) of the type IA topoisomerases harbor DNA cleavage and religation activities, but the carboxyl terminal domain (CTD) is highly diverse. Most of these enzymes contain a varied number of Zn2+ finger motifs in the CTD. The Zn2+ finger motifs were found to be essential in Escherichia coli topoI but dispensable in the Thermotoga maritima enzyme. Although, the CTD of mycobacterial topoI lacks Zn2+ fingers, it is indispensable for the DNA relaxation activity of the enzyme. The divergent CTD harbors three stretches of basic amino acids needed for the strand passage step of the reaction as demonstrated by a new assay. We also show that the basic amino acids constitute an independent DNA-binding site apart from the NTD and assist the simultaneous binding of two molecules of DNA to the enzyme, as required during the catalytic step. Although the NTD binds to DNA in a site-specific fashion to carry out DNA cleavage and religation, the basic residues in CTD bind to non-scissile DNA in a sequence-independent manner to promote the crucial strand passage step during DNA relaxation. The loss of Zn2+ fingers from the mycobacterial topoI could be associated with Zn2+ export and homeostasis.

SODAR observations of inertia- gravity waves in the atmospheric boundary layer during the passage of tropical cyclone

This study reports characteristics of inertia-gravity waves (IGWs) in the atmospheric boundary layer during the passage of Tropical Cylone-03B, using the Doppler Sound Detection and Ranging (SODAR) observations at the Indian tropical station of Gadanki (13.45 degrees N, 79.2 degrees E; near the east coast of India). Wavelet analysis of horizontal winds indicates significant wave motion (60h) near the characteristic inertial period. The hodograph analysis of the filtered winds shows an anti-cyclonic turning of horizontal wind with height and time, indicating the presence of IGW. This study finds important implications in boundary layer dynamics during the passage of tropical cyclones.

A Histidine Aspartate Ionic Lock Gates the Iron Passage in Miniferritins from Mycobacterium smegmatis

Background: DNA-binding protein from starved cells (Dps) are nano-compartments that can oxidize and store iron rendering protection from free radicals. Results: A histidine-aspartate ionic cluster in mycobaterial Dps2 modulates the rate of iron entry and exit in these proteins. Conclusion: Substitutions that disrupt the cluster interface alter the iron uptake/release properties with localized structural changes. Significance: Identifying important gating residues can help in designing nano-delivery vehicles. Dps (DNA-binding protein from starved cells) are dodecameric assemblies belonging to the ferritin family that can bind DNA, carry out ferroxidation, and store iron in their shells. The ferritin-like trimeric pore harbors the channel for the entry and exit of iron. By representing the structure of Dps as a network we have identified a charge-driven interface formed by a histidine aspartate cluster at the pore interface unique to Mycobacterium smegmatis Dps protein, MsDps2. Site-directed mutagenesis was employed to generate mutants to disrupt the charged interactions. Kinetics of iron uptake/release of the wild type and mutants were compared. Crystal structures were solved at a resolution of 1.8-2.2 for the various mutants to compare structural alterations vis a vis the wild type protein. The substitutions at the pore interface resulted in alterations in the side chain conformations leading to an overall weakening of the interface network, especially in cases of substitutions that alter the charge at the pore interface. Contrary to earlier findings where conserved aspartate residues were found crucial for iron release, we propose here that in the case of MsDps2, it is the interplay of negative-positive potentials at the pore that enables proper functioning of the protein. In similar studies in ferritins, negative and positive patches near the iron exit pore were found to be important in iron uptake/release kinetics. The unique ionic cluster in MsDps2 makes it a suitable candidate to act as nano-delivery vehicle, as these gated pores can be manipulated to exhibit conformations allowing for slow or fast rates of iron release.

1D Tight-Binding Models Render Quantum First Passage Time ``Speakable''

The calculation of First Passage Time (moreover, even its probability density in time) has so far been generally viewed as an ill-posed problem in the domain of quantum mechanics. The reasons can be summarily seen in the fact that the quantum probabilities in general do not satisfy the Kolmogorov sum rule: the probabilities for entering and non-entering of Feynman paths into a given region of space-time do not in general add up to unity, much owing to the interference of alternative paths. In the present work, it is pointed out that a special case exists (within quantum framework), in which, by design, there exists one and only one available path (i.e., door-way) to mediate the (first) passage -no alternative path to interfere with. Further, it is identified that a popular family of quantum systems - namely the 1d tight binding Hamiltonian systems - falls under this special category. For these model quantum systems, the first passage time distributions are obtained analytically by suitably applying a method originally devised for classical (stochastic) mechanics (by Schroedinger in 1915). This result is interesting especially given the fact that the tight binding models are extensively used in describing everyday phenomena in condense matter physics.

Optimal bounded control of first-passage failure of quasi-integrable Hamiltonian systems with wide-band random excitation

The optimal bounded control of quasi-integrable Hamiltonian systems with wide-band random excitation for minimizing their first-passage failure is investigated. First, a stochastic averaging method for multi-degrees-of-freedom (MDOF) strongly nonlinear quasi-integrable Hamiltonian systems with wide-band stationary random excitations using generalized harmonic functions is proposed. Then, the dynamical programming equations and their associated boundary and final time conditions for the control problems of maximizinig reliability and maximizing mean first-passage time are formulated based on the averaged It$\ddot{\rm o}$ equations by applying the dynamical programming principle. The optimal control law is derived from the dynamical programming equations and control constraints. The relationship between the dynamical programming equations and the backward Kolmogorov equation for the conditional reliability function and the Pontryagin equation for the conditional mean first-passage time of optimally controlled system is discussed. Finally, the conditional reliability function, the conditional probability density and mean of first-passage time of an optimally controlled system are obtained by solving the backward Kolmogorov equation and Pontryagin equation. The application of the proposed procedure and effectiveness of control strategy are illustrated with an example.

Enhanced virulence of Salmonella enterica serovar typhimurium after passage through mice.

The interaction between Salmonella enterica and the host immune system is complex. The outcome of an infection is the result of a balance between the in vivo environment where the bacteria survive and grow and the regulation of fitness genes at a level sufficient for the bacteria to retain their characteristic rate of growth in a given host. Using bacteriological counts from tissue homogenates and fluorescence microscopy to determine the spread, localization, and distribution of S. enterica in the tissues, we show that, during a systemic infection, S. enterica adapts to the in vivo environment. The adaptation becomes a measurable phenotype when bacteria that have resided in a donor animal are introduced into a recipient naïve animal. This adaptation does not confer increased resistance to early host killing mechanisms but can be detected as an enhancement in the bacterial net growth rate later in the infection. The enhanced growth rate is lost upon a single passage in vitro, and it is therefore transient and not due to selection of mutants. The adapted bacteria on average reach higher intracellular numbers in individual infected cells and therefore have patterns of organ spread different from those of nonadapted bacteria. These experiments help in developing an understanding of the influence of passage in a host on the fitness and virulence of S. enterica.

First-passage failure and its feedback minimization of quasi-partially integrable Hamiltonian systems

An n degree-of-freedom Hamiltonian system with r (1¡r¡n) independent 0rst integrals which are in involution is calledpartially integrable Hamiltonian system. A partially integrable Hamiltonian system subject to light dampings andweak stochastic excitations is called quasi-partially integrable Hamiltonian system. In the present paper, the procedures for studying the 0rst-passage failure and its feedback minimization of quasi-partially integrable Hamiltonian systems are proposed. First, the stochastic averaging methodfor quasi-partially integrable Hamiltonian systems is brie4y reviewed. Then, basedon the averagedIt ˆo equations, a backwardKolmogorov equation governing the conditional reliability function, a set of generalized Pontryagin equations governing the conditional moments of 0rst-passage time and their boundary and initial conditions are established. After that, the dynamical programming equations and their associated boundary and 0nal time conditions for the control problems of maximization of reliability andof maximization of mean 0rst-passage time are formulated. The relationship between the backwardKolmogorov equation andthe dynamical programming equation for reliability maximization, andthat between the Pontryagin equation andthe dynamical programming equation for maximization of mean 0rst-passage time are discussed. Finally, an example is worked out to illustrate the proposed procedures and the e9ectiveness of feedback control in reducing 0rst-passage failure.

First-passage failure of quasi-integrable Hamiltonian systems

The first-passage failure of quasi-integrable Hamiltonian si-stems (multidegree-of-freedom integrable Hamiltonian systems subject to light dampings and weakly random excitations) is investigated. The motion equations of such a system are first reduced to a set of averaged Ito stochastic differential equations by using the stochastic averaging method for quasi-integrable Hamiltonian systems. Then, a backward Kolmogorov equation governing the conditional reliability function and a set of generalized Pontryagin equations governing the conditional moments of first-passage time are established. Finally, the conditional reliability function, and the conditional probability density and moments of first-passage time are obtained by solving these equations with suitable initial and boundary conditions. Two examples are given to illustrate the proposed procedure and the results from digital simulation are obtained to verify the effectiveness of the procedure.

First-passage time of Duffing oscillator under combined harmonic and white-noise excitations

The first-passage time of Duffing oscillator under combined harmonic and white-noise excitations is studied. The equation of motion of the system is first reduced to a set of averaged Ito stochastic differential equations by using the stochastic averaging method. Then, a backward Kolmogorov equation governing the conditional reliability function and a set of generalized Pontryagin equations governing the conditional moments of first-passage time are established. Finally, the conditional reliability function, and the conditional probability density and moments of first-passage time are obtained by solving the backward Kolmogorov equation and generalized Pontryagin equations with suitable initial and boundary conditions. Numerical results for two resonant cases with several sets of parameter values are obtained and the analytical results are verified by using those from digital simulation.

Optimal bounded control of first-passage failure of strongly non-linear oscillators under combined harmonic and white-noise excitations

A procedure for designing the optimal bounded control of strongly non-linear oscillators under combined harmonic and white-noise excitations for minimizing their first-passage failure is proposed. First, a stochastic averaging method for strongly non-linear oscillators under combined harmonic and white-noise excitations using generalized harmonic functions is introduced. Then, the dynamical programming equations and their boundary and final time conditions for the control problems of maximizing reliability and of maximizing mean first-passage time are formulated from the averaged Ito equations by using the dynamical programming principle. The optimal control law is derived from the dynamical programming equations and control constraint. Finally, the conditional reliability function, the conditional probability density and mean of the first-passage time of the optimally controlled system are obtained from solving the backward Kolmogorov equation and Pontryagin equation. An example is given to illustrate the proposed procedure and the results obtained are verified by using those from digital simulation. (C) 2003 Elsevier Ltd. All rights reserved.

A Passage to India: from novel to film. Some problems of "translation"

Eguíluz, Federico; Merino, Raquel; Olsen, Vickie; Pajares, Eterio; Santamaría, José Miguel (eds.)