Ring flexibility within tricyclic antidepressant drugs

The internal flexibility of the central seven-membered ring of a series of tricyclic antidepressant drugs (TCAs), imipramine {l}, amitriptyline {2}, doxepin {3}, and dothiepin {4}, has been investigated by H-1 and C-13 nuclear magnetic (NMR) techniques. Two dynamic processes were examined: ring inversion and bridge flexing. H-1 NMR lineshape analysis was used to obtain ring inversion barriers for 2-4. These studies yielded energy barriers of 14.3, 16.7, and 15.7 +/- 0.6 kcal/mol for the hydrochloride salts of doxepin, dothiepin, and amitriptyline, respectively. The barriers for the corresponding free bases were lower by 0.6 kcal/mol on average. (CT1)-C-13 relaxation measurements were used to determine the degree of bridge flexing associated with the central seven-membered ring for all four compounds. By fitting the T-1 data to a two-state jump model, lifetimes and amplitudes of rapid bridge flexing motions were determined. The results show that imipramine has the fastest rate of bridge flexing, followed by amitriptyline, doxepin, and dothiepin. The pharmacological profiles of the TCAs are complex and they interact with many receptor sites, resulting in numerous side effects and a general lack of understanding of their precise mode of action in different anxiety-related disorders. They all have similar three-dimensional structures, which makes it difficult to rationalize their differing relative potency in different assays/clinical settings. However, the clear finding here that there are significantly different degrees of internal mobility suggests that molecular dynamics should be an additional factor considered when trying to understand the mode of action of this clinically important family of molecules. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:713-721, 2001.

Briefing: Factored material properties and limit state loads-unlikely extreme or impossible pretense

In the limit state design (LSD) method each design criterion is formally stated and assessed using a performance function. The performance function defines the relationship between the design parameters and the design criterion. In practice, LSD involves factoring up loads and factoring down calculated strengths and material parameters. This provides a convenient way to carry out routine probabilistic-based design. The factors are statistically calculated to produce a design with an acceptably low probability of failure. Hence the ultimate load and the design material properties are mathematical concepts that have no physical interpretation. They may be physically impossible. Similarly, the appropriate analysis model is also defined by the performance function and may not describe the real behaviour at the perceived physical equivalent limit condition. These points must be understood to avoid confusion in the discussion and application of partial factor LSD methods.

Noise-free scattering of the quantized electromagnetic field from a dispersive linear dielectric

We study the scattering of the quantized electromagnetic field from a linear, dispersive dielectric using the scattering formalism for quantum fields. The medium is modeled as a collection of harmonic oscillators with a number of distinct resonance frequencies. This model corresponds to the Sellmeir expansion, which is widely used to describe experimental data for real dispersive media. The integral equation for the interpolating field in terms of the in field is solved and the solution used to find the out field. The relation between the ill and out creation and annihilation operators is found that allows one to calculate the S matrix for this system. In this model, we find that there are absorption bands, but the input-output relations are completely unitary. No additional quantum-noise terms are required.

Calculation of product state distributions from resonance decay via Lanczos subspace filter diagonalization: Application to HO2

Resonance phenomena associated with the unimolecular dissociation of HO2 have been investigated quantum-mechanically by the Lanczos homogeneous filter diagonalization (LHFD) method. The calculated resonance energies, rates (widths), and product state distributions are compared to results from an autocorrelation function-based filter diagonalization (ACFFD) method. For calculating resonance wave functions via ACFFD, an analytical expression for the expansion coefficients of the modified Chebyshev polynomials is introduced. Both dissociation rates and product state distributions of O-2 show strong fluctuations, indicating the dissociation of HO2 is essentially irregular. (C) 2001 American Institute of Physics.

Assessment and management of dysphagia following pharyngolaryngectomy with free jejunal interposition: A series of eight case studies

The physiological and structural deficits contributing to swallowing complications in the pharyngolaryngectomy patient population are not homogeneous. Consequently, a team approach, involving medical investigations as well as clinical and radiological assessments of swallowing, is necessary to facilitate diagnosis of the underlying impairment and assist the medical/surgical and speech pathology team members in the process of individualizing the management plan for each patient. In the present study, the clinical assessment and management of eight pharyngolaryngectomy patients who presented with a decline in swallowing function unrelated to immediate postsurgical effects or direct effects of radiotherapy are reported. Clinical and radiological investigations revealed a heterogeneous group of factors contributing to their swallowing impairments and disability levels, including difficulty with graft and anastomotic patency and graft motility, impaired lingual coordination, increased bolus transit time, nasal and oral regurgitation, patient distress, and recurrence. Variation between the cases supported the need for differential intervention and management plans for all eight patients. Ratings of perceived swallowing disability, handicap, and well-being/distress levels at initial assessment and again six months following dysphagia intervention revealed a pattern of reduced levels of impairment, functional disability, and overall patient distress levels following informed intervention. The present case study data highlights the key role thorough clinical and radiological investigations play in the process of diagnosing the factors contributing to dysphagia and guiding the management of the resultant swallowing disability in the pharyngolaryngectomy population.

Universal state inversion and concurrence in arbitrary dimensions

Wootters [Phys. Rev. Lett. 80, 2245 (1998)] has given an explicit formula for the entanglement of formation of two qubits in terms of what he calls the concurrence of the joint density operator. Wootters's concurrence is defined with the help of the superoperator that flips the spin of a qubit. We generalize the spin-flip superoperator to a universal inverter, which acts on quantum systems of arbitrary dimension, and we introduce the corresponding generalized concurrence for joint pure states of D-1 X D-2 bipartite quantum systems. We call this generalized concurrence the I concurrence to emphasize its relation to the universal inverter. The universal inverter, which is a positive, but not completely positive superoperator, is closely related to the completely positive universal-NOT superoperator, the quantum analogue of a classical NOT gate. We present a physical realization of the universal-NOT Superoperator.

Phase sensitive pumping and coherence of superposition states

The continuous parametric pumping of a superconducting lossy QED cavity supporting a field prepared initially as a superposition of coherent states is discussed. In contrast to classical pumping, we verify that the phase sensitivity of the parametric pumping makes the asymptotic behaviour of the cavity field state strongly dependent on the phase theta of the coherent state \ alpha > = \ alpha \e(i theta)>. Here we consider theta = pi /4, -pi /4 and we analyse the evolution of the purity of the superposition states with the help of the linear entropy and fidelity functions. We also analyse the decoherence process quantitatively through the Wigner function, for both states, verifying that the decay is slightly modified when compared to the free decoherence case: for theta = -pi /4 the process is accelerated while for theta = pi /4 it is delayed.

Feedback-stabilization of an arbitrary pure state of a two-level atom

Unit-efficiency homodyne detection of the resonance fluorescence of a two-level atom collapses the quantum state of the atom to a stochastically moving point on the Bloch sphere. Recently, Hofmann, Mahler, and Hess [Phys. Rev. A 57, 4877 (1998)] showed that by making part of the coherent driving proportional to the homodyne photocurrent one can stabilize the state to any point on the bottom-half of the sphere. Here we reanalyze their proposal using the technique of stochastic master equations, allowing their results to be generalized in two ways. First, we show that any point on the upper- or lower-half, but not the equator, of the sphere may be stabilized. Second, we consider nonunit-efficiency detection, and quantify the effectiveness of the feedback by calculating the maximal purity obtainable in any particular direction in Bloch space.