Orbital motion of spiral waves in excitable media.

Spiral waves in active media react to small perturbations as particlelike objects. Here we apply asymptotic theory to the interaction of spiral waves with a localized inhomogeneity, which leads to a novel prediction: drift of the spiral rotation center along circular orbits around the inhomogeneity. The stationary orbits have fixed radii and alternating stability, determined by the properties of the bulk medium and the type of inhomogeneity, while the drift speed along an orbit depends on the strength of the inhomogeneity. Direct numerical simulations confirm the validity and robustness of the theoretical predictions and show that these unexpected effects should be observable in experiment.

Alternative stable scroll waves and conversion of autowave turbulence.

Rotating spiral and scroll waves (vortices) are investigated in the FitzHugh-Nagumo model of excitable media. The focus is on a parameter region in which there exists bistability between alternative stable vortices with distinct periods. Response functions are used to predict the filament tension of the alternative scrolls and it is shown that the slow-period scroll has negative filament tension, while the filament tension of the fast-period scroll changes sign within a hysteresis loop. The predictions are confirmed by direct simulations. Further investigations show that the slow-period scrolls display features similar to delayed after-depolarization and tend to develop into turbulence similar to ventricular fibrillation (VF). Scrolls with positive filament tension collapse or stabilize, similar to monomorphic ventricular tachycardia (VT). Perturbations, such as boundary interaction or shock stimulus, can convert the vortex with negative filament tension into the vortex with positive filament tension. This may correspond to transition from VF to VT unrelated to pinning.

Adenosine-3',5'-phosphate: identification as acrasin in a species of cellular slime mold.

Acrasin, the chemotactic agent responsible for aggregation in thecellular slime molds, has been identified for one species, Dictyostelium discoideum, as adenosine-3', 5'-phosphate.

Huntington's disease: delayed hypersensitivity in vitro to human central nervous system antigens.

Huntington's disease is a hereditary, chronic, degenerative disease of the brain which is transmitted by an autosomal dominant gene. We have discovered that lymphocytes from patients with Huntington's disease respond to the presence of brain tissue from patients with the disease by producing migration inhibition factor, a correlate of the cellular immune response. Lymphocytes from donors without the disease do not respond to the diseased brain tissue, and lymphocytes from patients with Huntington's disease respond only rarely to brain tissue from donors without the disease.

Computation of the response functions of spiral waves in active media.

Rotating spiral waves are a form of self-organization observed in spatially extended systems of physical, chemical, and biological natures. A small perturbation causes gradual change in spatial location of spiral's rotation center and frequency, i.e., drift. The response functions (RFs) of a spiral wave are the eigenfunctions of the adjoint linearized operator corresponding to the critical eigenvalues lambda=0,+/-iomega. The RFs describe the spiral's sensitivity to small perturbations in the way that a spiral is insensitive to small perturbations where its RFs are close to zero. The velocity of a spiral's drift is proportional to the convolution of RFs with the perturbation. Here we develop a regular and generic method of computing the RFs of stationary rotating spirals in reaction-diffusion equations. We demonstrate the method on the FitzHugh-Nagumo system and also show convergence of the method with respect to the computational parameters, i.e., discretization steps and size of the medium. The obtained RFs are localized at the spiral's core.

Cellular immune responses in Huntington disease. Specificity of brain antigenicity detected with Huntington disease lymphocytes.

This study confirms the production of migration inhibition factor by Huntington disease lymphocytes in response to antigen found in Huntington disease but not normal brain tissue. Huntington disease lymphocytes also respond to the presence of multiple sclerosis brain tissue with migration inhibition factor production.

The detection by immunofluorescence of distinct cell populations producing interleukin-1 alpha and interleukin-1 beta in activated human peripheral blood.

An immunofluorescent staining method using specific monoclonal antibodies was used to detect IL-1 alpha and IL-1 beta in individual cells in stimulated human peripheral blood. No staining was seen in unstimulated cells but intense, maximal staining of approximately 5% of the cells was seen 20-24 h after activation with PHA/PMA. The large irregularly shaped stained cells were surrounded by smaller unstained cells with lymphocyte-like morphology. By 44 h post activation a few cells only showed weak staining. The staining pattern was different for the two molecules studied, with a granular pattern for IL-1 alpha staining and diffuse cytoplasmic staining for IL-1 beta. Staining post-activation could be abolished by preincubation of the monoclonal antibody with the appropriate recombinant IL-1, but not by pre-incubation with the other IL-1 type. When both anti-IL-1 alpha and anti-IL-1 beta were used together two populations of cells were identified; one had the granular staining as seen with anti-IL-1 alpha alone and the other had the diffuse staining pattern as seen with anti-IL-1 beta. The percentage of cells showing bright staining with anti-IL-1 alpha and anti-IL-1 beta together was approximately equal to the sum of the percentage of cells staining for IL-1 alpha or IL-1 beta alone. This study demonstrates a method for the detection of individual IL-1 alpha- and IL-1 beta- producing cells and suggests that in activated human peripheral blood IL-1 alpha and IL-1 beta are produced by separate populations of cells.

Evaluation of an inservice training program on dementia and wandering.

This study assessed the impact of an inservice training program in four nursing homes on nursing staff's knowledge of dementia, pacing/wandering behavior and management strategies, staff satisfaction, and their perceptions of work difficulty and quality of care. Additionally, unit-level behavioral observations of agitated behavior and the nature of resident interactions with staff members and other residents were also performed to assess whether changes in nursing staff's knowledge impacted the residents or interactions with the residents. Analyses revealed that quiz scores were significantly improved immediately following the inservice program as compared to pretest but returned to near pretest levels at the 1-month follow-up. Additionally, nursing staff reported that residents were allowed to pace/wander to a greater extent at follow-up compared to pretest. Methods for improving the effectiveness of inservice training are discussed.

The role of local school quality in rural employment and population growth.

"This study investigates the influence of school quality (measured at the high school level) on 1980 to 1990 population and employment change for nonmetropolitan fringe and hinterland census tracts in South Carolina. A Boarnet variation of the Carlino-Mills model is used to examine the interdependence of population and employment change.... Results...indicate that fringe tracts' population growth was positively related to student test scores, and hinterland tracts population and employment growth were negatively related to student-teacher ratios. Empirical results suggest that local school quality provided a positive influence on rural growth, primarily in terms of residential growth. The role of school quality for employment growth was less clear."

Computational study of subcritical response in flow past a circular cylinder.

Flow past a circular cylinder is investigated in the subcritical regime, below the onset of Bénard-von Kármán vortex shedding at Reynolds number Re(c)≃47 . The transient response of infinitesimal perturbations is computed. The domain requirements for obtaining converged results is discussed at length. It is shown that energy amplification occurs as low as Re=2.2 . Throughout much of the subcritical regime the maximum energy amplification increases approximately exponentially in the square of Re reaching 6800 at Re(c). The spatiotemporal structure of the optimal transient dynamics is shown to be transitory Bénard-von Kármán vortex streets. At Re≃42 the long-time structure switches from exponentially increasing downstream to exponentially decaying downstream. Three-dimensional computations show that two-dimensional structures dominate the energy growth except at short times.

Computation of the drift velocity of spiral waves using response functions.

Rotating spiral waves are a form of self-organization observed in spatially extended systems of physical, chemical, and biological nature. In the presence of a small perturbation, the spiral wave's center of rotation and fiducial phase may change over time, i.e., the spiral wave drifts. In linear approximation, the velocity of the drift is proportional to the convolution of the perturbation with the spiral's response functions, which are the eigenfunctions of the adjoint linearized operator corresponding to the critical eigenvalues λ=0,±iω . Here, we demonstrate that the response functions give quantitatively accurate prediction of the drift velocities due to a variety of perturbations: a time dependent, periodic perturbation (inducing resonant drift); a rotational symmetry-breaking perturbation (inducing electrophoretic drift); and a translational symmetry-breaking perturbation (inhomogeneity induced drift) including drift due to a gradient, stepwise, and localized inhomogeneity. We predict the drift velocities using the response functions in FitzHugh-Nagumo and Barkley models, and compare them with the velocities obtained in direct numerical simulations. In all cases good quantitative agreement is demonstrated.

Modeling the dynamics of cardiac action potentials.

The nonlinear dynamics of cardiac action potentials is explained via simple model equations describing the membrane potential and the inward and outward currents through the membrane. The equations approximate ionic models, yet are expressed as polynomial functions, and robustly capture the phase-space dynamics of action potentials.

Selection of twisted scroll waves in three-dimensional excitable media.

The selection of shape and rotation frequency for scroll waves in reaction-diffusion equations modeling excitable media is investigated. For scrolls with uniform twist about straight filaments, asymptotic methods are used to derive free-boundary equations at leading and first order. Both orders are validated against full solutions of the reaction-diffusion equations. Using these two orders and with no adjustable parameters, the shape and frequency of waves are correctly predicted except possibly near the point of propagation failure where the core becomes large.

Increased expression of HLA-DQ antigens by interstitial cells and endothelium in the synovial membrane of rheumatoid arthritis patients compared with reactive arthritis patients.

We investigated cellular phenotypes and expression of class II major histocompatibility complex antigens on endothelium and cellular infiltrates in synovium from patients with rheumatoid arthritis (RA) or reactive arthritis, using an indirect immunoperoxidase technique. The RA specimens showed synovial lining layer hypertrophy and several focal accumulations of lymphocytes, both of which were absent in the reactive arthritis synovium. The percentage of cells expressing monocyte/macrophage markers was significantly higher in RA specimens. The percentages of cells expressing B and T cell markers were similar in both diseases. There was no significant difference in the expression of HLA-DR or DP by endothelium in the 2 diseases, but a marked increase in expression of HLA-DQ by endothelium was observed in the RA synovium versus that from patients with reactive arthritis. This overexpression of HLA-DQ was also seen in the interstitial cells of RA patients compared with reactive arthritis patients. In the reactive arthritis synovium, a significant population of cells (30%) was noted to be HLA-DR positive, and negative for macrophage and lymphocyte markers. Some of these cells had a dendritic morphology. The coexpression of HLA-DQ and HLA-DR may play an important role in antigen presentation and disease chronicity in RA.

Cells with dendritic morphology and bright interleukin-1 alpha staining circulate in the blood of patients with rheumatoid arthritis.

Freshly isolated peripheral blood mononuclear cells (PBMC) from 10 healthy volunteers, 28 patients with rheumatoid arthritis (RA), eight patients with osteoarthritis, and five patients with ankylosing spondylitis were examined for interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) production using monoclonal antibodies and an indirect immunofluorescent method. In freshly isolated PBMC from healthy controls very few cells were stained for either IL-1 type. All 20 RA patients who were not receiving parenteral gold therapy had PBMC staining for IL-1 alpha. In these patients, up to 7.5% of PBMC showed bright IL-1 alpha staining (range 1.2-7.5%). No IL-1 beta staining was seen. These IL-1 alpha-staining cells had a dendritic morphology and the percentage of cells staining correlated well with levels of C-reactive protein, an index of disease activity in these RA patients. Significantly fewer IL-1 alpha-staining cells were present in the peripheral blood of RA patients receiving gold therapy and in the blood of patients with osteoarthritis and ankylosing spondylitis. These IL-1 alpha-containing cells, circulating in the blood of RA patients and correlating with disease activity have not been previously described. These results support the idea that IL-1 alpha plays an important role in the pathogenesis of rheumatoid inflammation.