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.)

Universal quantum computation with trapped ions in thermal motion by adiabatic passage

We propose a universal quantum computation scheme for trapped ions in thermal motion via the technique of adiabatic passage, which incorporates the advantages of both the adiabatic passage and the model of trapped ions in thermal motion. Our scheme is immune from the decoherence due to spontaneous emission from excited states as the system in our scheme evolves along a dark state. In our scheme the vibrational degrees of freedom are not required to be cooled to their ground states because they are only virtually excited. It is shown that the fidelity of the resultant gate operation is still high even when the magnitude of the effective Rabi frequency moderately deviates from the desired value.

Stimulated Raman adiabatic passage from atomic to molecular Bose-Einstein condensates: Feedback laser-detuning control and suppression of dynamical instability

We present a feedback control scheme that designs time-dependent laser-detuning frequency to suppress possible dynamical instability in coupled free-quasibound-bound atom-molecule condensate systems. The proposed adaptive frequency chirp with feedback is shown to be highly robust and very efficient in the passage from an atomic to a stable molecular Bose-Einstein condensate.

Fish pass design - criteria for the design and approval of fish passes and other structures to facilitate the passage of migratory fish in rivers

Many of British rivers hold stocks of salmon (Salmo salar L.) and sea trout (Salmo trutta L.) and during most of the year some of the adult fish migrate upstream to the head waters where, with the advent of winter, they will eventually spawn. For a variety of reasons, including the generation of power for milling, improving navigation and measuring water flow, man has put obstacles in the way of migratory fish which have added to those already provided by nature in the shape of rapids and waterfalls. While both salmon and sea trout, particularly the former, are capable of spectacular leaps the movement of fish over man-made and natural obstacles can be helped, or even made possible, by the judicious use of fish passes. These are designed to give the fish an easier route over or round an obstacle by allowing it to overcome the water head difference in a series of stages ('pool and traverse' fish pass) or by reducing the water velocity in a sloping channel (Denil fish pass). Salmon and sea trout make their spawning runs at different flow conditions, salmon preferring much higher water flows than sea trout. Hence the design of fish passes requires an understanding of the swimming ability of fish (speed and endurance) and the effect of water temperature on this ability. Also the unique features of each site must be appreciated to enable the pass to be positioned so that its entrance is readily located. As well as salmon and sea trout, rivers often have stocks of coarse fish and eels. Coarse fish migrations are generally local in character and although some obstructions such as weirs may allow downstream passages only, they do not cause a significant problem. Eels, like salmon and sea trout, travel both up and down river during the course of their life histories. However, the climbing power of elvers is legendary and it is not normally necessary to offer them help, while adult silver eels migrate at times of high water flow when downstream movement is comparatively easy: for these reasons neither coarse fish nor eels are considered further. The provision of fish passes is, in many instances, mandatory under the Salmon and Freshwater Fisheries Act 1975. This report is intended for those involved in the planning, siting, construction and operation of fish passes and is written to clarify the hydraulic problems for the biologist and the biological problems for the engineer. It is also intended to explain the criteria by which the design of an individual pass is assessed for Ministerial Approval.

A survey of estuarine oxygen concentrations in relation to the passage of migratory salmonids

This report presents the first attempt at a national assessment of an Environmental Quality Standard (EQS) for dissolved oxygen (DO) in estuaries with the objective of allowing the passage of migratory salmonids. Under the Control of Pollution Act, Water Authorities and River Purification Boards have powers to control discharges to estuaries and need to define an EQS for the calculation of consent conditions. The object of any such standards is to permit the existence of good quality salmonid fisheries with only very occasional restrictions to the passage of fish. The report gives brief summaries of the DO regime in estuaries, the oxygen requirements of salmonids, and of tentative standards proposed by various authorities. These standards are then compared with DO and fishery data from UK estuaries, provided by the appropriate regulatory authorities. It concludes that a minimum annual lower 95-percentile of 5.0 mg/1 will meet the objective in most estuaries, and that a lower value of 3.0 mg/1 will permit the establishment of a more restricted fishery. However, more stringent standards may be needed in estuaries containing high concentrations of toxic pollutants. containing high concentrations of toxic pollutants.