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Biomedical subjects

W J Firth

Publications and source records attributed to W J Firth.

17 recordsLinked to original sources
PubMed2002

Computationally determined existence and stability of transverse structures. I. Periodic optical patterns.

We present a Fourier-transform based, computer-assisted, technique to find the stationary solutions of a model describing a saturable absorber in a driven optical cavity. We illustrate the method by finding essentially exact hexagonal and roll solutions as a function of wave number and of the input pump. The method, which is widely applicable, also allows the determination of the domain of stability (Busse balloon) of the pattern, and sheds light on the mechanisms responsible for any instability. To show the usefulness of our numerical technique, we describe cracking and shrinking patches of patterns in a particular region of parameter space.

Journal Article↗
PubMed2002

Computationally determined existence and stability of transverse structures. II. Multipeaked cavity solitons.

We apply quasi-exact numerical techniques to the calculation of stationary one- and two-dimensional, bound multipeaked cavity soliton solutions of a model describing a saturable absorber in a driven optical cavity. We calculate the existence and stability domains of a wide range of such states and determine the perturbative eigenmodes that cause loss of stability. We relate the existence of N-peaked states to the locking range between patterned and homogeneous solutions, as a function of two parameters.

Journal Article↗
PubMed2002

Self-propelled cavity solitons in semiconductor microcavities.

We demonstrate the existence of both bright and dark spontaneously moving spatial solitons in a model of a semiconductor microcavity. The motion is caused by temperature-induced changes in the cavity detuning and arises through an instability of the stationary soliton solution above some threshold. An order parameter equation is derived for the moving solitons and is used to explain their behavior in the presence of externally imposed parameter modulations. The existence of two-dimensional moving solitons is demonstrated and an example given of their interaction.

Journal Article↗
PubMed2001

Perturbation theory for domain walls in the parametric Ginzburg-Landau equation.

We demonstrate that in the parametrically driven Ginzburg-Landau equation arbitrarily small nongradient corrections lead to qualitative differences in the dynamical properties of domain walls in the vicinity of the transition from rest to motion. These differences originate from singular rotation of the eigenvector governing the transition. We present analytical results on the stability of Ising walls, deriving explicit expressions for the critical eigenvalue responsible for the transition from rest to motion. We then develop a weakly nonlinear theory to characterize the singular character of the transition and analyze the dynamical effects of spatial inhomogeneities.

Journal Article↗
PubMed2001

Characterization, dynamics and stabilization of diffractive domain walls and dark ring cavity solitons in parametric oscillators.

Mean field models of spatially extended degenerate optical parametric oscillators possess one-dimensional stable domain wall solutions in the presence of diffraction. We characterize these structures as spiral heteroclinic connections and study the spatial frequency of the local oscillations of the signal intensity which distinguish them from diffusion kinks. Close to threshold, at resonance or with positive detunings, the dynamics of two-dimensional diffractive domain walls is ruled by curvature effects with a t(1/2) growth law, and coalescence of domains is observed. In this regime, we show how to stabilize regular and irregular distributions of two-dimensional domain walls by injection of a helical wave at the pump frequency. Further above threshold the shrinking of domains of one phase embedded in the other is stopped by the interaction of the oscillatory tails of the domain walls, leading to cavity solitons surrounded by a characteristic dark ring. We investigate the nature and stability of these localized states, provide evidence of their solitonic character, show that they correspond to spiral homoclinic orbits and find that their threshold of appearance lowers with increasing pump cavity finesse.

Journal Article↗
PubMed2001

Universal criterion and amplitude equation for a nonequilibrium Ising-Bloch transition.

We identify a universal criterion for the onset of a nonequilibrium Ising-Bloch (NIB) transition, and describe the behavior near the bifurcation by a generic amplitude equation. We found that a NIB transition is caused by an antisymmetric eigenvector passing the translational mode of the system at a critical point. In this context we discuss Hamiltonian and dissipative systems. We report on a NIB in nonlinear optics, manifesting itself in a transition from static to moving polarization fronts.

Journal Article↗
PubMed1999

Modulational instability of bright solitary waves in incoherently coupled nonlinear Schrödinger equations.

We present a detailed analysis of the modulational instability (MI) of ground-state bright solitary solutions of two incoherently coupled nonlinear Schrödinger equations. Varying the relative strength of cross-phase and self-phase effects we show the existence and origin of four branches of MI of the two-wave solitary solutions. We give a physical interpretation of our results in terms of the group-velocity-dispersion- (GVD-) induced polarization dynamics of spatial solitary waves. In particular, we show that in media with normal GVD spatial symmetry breaking changes to polarization symmetry breaking when the relative strength of the cross-phase modulation exceeds a certain threshold value. The analytical and numerical stability analyses are fully supported by an extensive series of numerical simulations of the full model.

Journal Article↗
PubMed1984

Induction of cytoplasmically inherited respiration-deficient ('petite') mutants by photodynamic action of acridine compounds.

All acridines used (acriflavine, proflavine, acridine orange and 3-azido-10-methylacridinium chloride) produced killing in yeast cells when activated with visible light. Acriflavine, proflavine and 3-azido-10-methylacridinium chloride, but not acridine orange, produced petite and sectored colonies. Both cell killing and petite induction by light activation of acriflavine resulted apparently from photodynamic action mediated by singlet oxygen (1O2) since the effect were prevented by either sodium azide or anaerobiosis. The biological effects of 3-azido-10-methylacridinium chloride, which was developed as a potential photoaffinity probe for studying the binding and biological effects of acridines, appeared to be due to a photodynamic action analogous to that of acriflavine. Sodium azide or anaerobiosis prevented the light-activated effects of 3-azido-10-methylacridinium chloride despite the fact that the initial chemical breakdown of the azido derivative induced by light was not affected. Cells suspended in D2O demonstrated an enhanced response to 3-azido-10-methylacridinium chloride with irradiation. These results indicate that singlet oxygen mediates the light-activated biological effects of both acriflavine and 3-azido-10-methylacridinium chloride.

Acridines↗
PubMed1984

Identification of an acridine photoaffinity probe for trypanocidal action.

Twenty-four acridine derivatives were screened for trypanocidal activity in Trypanosoma brucei in order to determine which structural features of the acridine molecule confer maximal antiparasitic activity. The synthesis of several new azidoacridine derivatives are also reported as well as an assessment of their value as possible photoaffinity probes for the study of acridine trypanocidal action. The most effective and selective acridine trypanocides, with and without irradiation, were the 3-amino-10-methylacridinium salt derivatives. With brief irradiation, one azidoacridine, 3-amino-6-azido-10-methylacridinium chloride, showed considerable trypanocidal activity at very limiting drug concentrations (10(-7)M) and warrants consideration as a possible photoaffinity probe.

Acridines↗
PubMed1981

Azido analogs of acridine: photoaffinity probes for frameshift mutagenesis in Salmonella typhimurium.

In order to identify a photoaffinity probe for 9-aminoacridine frameshift mutagenesis, 20 azido analogs of acridine were synthesized and tested in Ames' Salmonella tester strains, TA1535, TA1537, TA1538 and their corresponding excision-repair-coefficient strains TA1975, TA1977 and TA1978, to determine their mutagenicity and toxicity relative to 9-aminoacridine. The substituent-mutagenicity patterns observed for these compounds agree very well with those obtained previously for non-azidoacridines. The results presented here show that the 2-azido-analog of 9-aminoacridine demonstrates biological activity similar to 9-aminoacridine prior to photolytic activation. With light activation, however, the 9-amino-2-azido derivative becomes more effective at producing frameshift mutations characteristic of 9-aminoacridine. Furthermore, this photolytic enhancement of mutagenesis appears to be due to the repairable lesion suggesting that covalent attachment of the drug occurs.

Acridines↗
PubMed1981

Comparison of petite induction in yeast by acridines, ethidium and their photoaffinity probes.

The production of petite mutations by different acridine analogs was studied in Saccharomyces cerevisiae. Compounds with amino substituents at the 2 and 3 positions of the acridine nucleus and methylation at position 10 were effective for petite induction in growing cells but not in resting cells, while those with chloro, nitro and methoxy substituents were not effective in either resting or growing cells. Photosensitive azido derivatives of the acridines were tested to evaluate the role of covalent drug attachment for mutagenesis in resting cells. Photolysis of resting cells with 9-axido, 3-azido-6-amino-, 9-azido-10-methyl-, or 3-azido-6-amino-10-methyl-acridine was highly toxic. 3-Azido-6-amino-acridine, and especially 3-azido-10-methyl-, and 3-azido-6-amino-10-methyl-acridine, were effective petite inducers in resting cells. Thus, the photosensitive (azido) group at position 9 produced only cell killing while the azido group at position 3 and/or 6 led to effective petite induction in resting cells. In contrast, petite induction was observed only for growing cells, for dark control experiments with these compounds or with the monoazide precursor compounds.

Acridines↗
PubMed1981

Antitrypanosomal action enhanced by photoaffinity labeling with ethidium analogs.

The trypanocidal activity of photoreactive azido analogs of ethidium was tested to determine the suitability of using such compounds as in vivo probes to study the mechanism of the antitrypanosomal activity of ethidium. Eight ethidium analogs, including three nonphotoreactive compounds, were tested for their ability to kill T. brucei both with and without photolytic activation. Two analogs tested, the monoamino-monoazido isomers, showed greater that 100-fold enhancement of trypanocidal activity following photolytic activation in situ. Without photolytic activation, only the nonphotoreactive monoamino precursor analogs showed activity greater than the parent ethidium compound. The availability of suitable ethidium analogs which can be covalently attached by in situ photoactivation provides a new approach for studying the mechanism by which ethidium exerts its trypanocidal activity.

Animals↗
PubMed1980

Structure-function characterization for ethidium photoaffinity labels as mutagens in Salmonella.

The development of photoaffinity probes to characterize the binding process and subsequent biological activity of a drug has recently been emphasized by the synthesis of two ethidium azide analogs. The initial finding showed that one of the azido analogs, the 8-azido-3-amino derivative, was at least 40-fold more mutagenic and toxic in Salmonella tester strain TA1538 than the other analog, the 3.8-diazido derivative. These observations suggested the need to examine the structural requirements of ethidium photoaffinity labels for frameshift mutagenic activity in Salmonella. Thus, the isomer of the monoazide, the 3-azido-8-amino derivative, and two deaminated monoazide derivatives were synthesized and all of the ethidium analogs were screened in two Salmonella frameshift tester strains, TA1537 and TA1538, and in their excision-repair positive isogenic strains. The results presented in this paper demonstrate that two substituents are needed to produce significant mutagenicity and toxicity by the compound. One substituent, usually the amino group, is required for mutagenic activity, perhaps by orienting the phenanthridinium ring into its mutagenic configuration. The other substituent, the azido group, is required for covalent attachment, a requisite for mutagenic activity. Thus, photoaffinity labeling has provided a means of comparing structure with mutagenic activity for ethidium compounds.

Affinity Labels↗
PubMed1980

Acridine structure correlated with mutagenic activity in Salmonella.

The structural basis for direct mutagenicity of acridines was studied by testing 50 different analogs in the Ames Salmonella tester strains without the addition of mammalian activating enzymes. These experiments showed that the single most effective substituent for frameshift mutagenesis in strain TA1537 is an amino group at the "9" position, while an amino group at either the "3" or "1" position is less effective. Other substitutions at the "9" position demonstrate decreased frameshifting activity compared to 9-aminoacridine. Furthermore, all substituents in combination with the amino group of 9-aminoacridine also decrease frameshifting activity, except for the addition of another amino group at the "1" position or a methyl at the ring nitrogen. Nitro substituents at the "1" and "3" positions enhance 9-aminoacridine toxocity. All nitro substituents decrease typical acridine-frameshift mutagenesis for strain TA1537, but they induce mutagenic activity either in the other type of frameshift strain, TA1538, or in the base-pair substitution strain TA1535. These studies have provided important structure-function relationships for acridine mutagenicity and toxicity in Salmonella. Consequently, this biological system has provided a sensitive means for determining the structural requirements for mutagenic mechanisms.

Acridines↗
PubMed1980

Petite induction in Saccharomyces cerevisiae by ethidium analogs: distinction between resting and growing cells.

The importance of specific substituents, especially amino azide groups, for ethidium induction of petites was evaluated in resting and dividing cells of Saccharomyces cerevisiae through the study of a series of ethidium analogs. The structural requirements in resting and growing cells were found to be different, suggesting that at least two mechanisms are responsible for induction. The significance of particular substituents in the induction processes were recognized by: (1) a dependence upon the ethyl substituent at the ring nitrogen in both actively growing and in resting cells; and (2) the implication that amino substituents are important for the effect in dividing cells and especially in resting cells. Photolytic enhancement of petite induction (via a nitrene which forms a covalent linkage to a biological site) was observed for 3 of the azide analogs, which emphasizes the likelihood that metabolic activation of ethidium to a covalent complex is responsible for its effectiveness. Furthermore, these studies indicate that these monoazide analogs should be ideal probes for examining the mitochondrial mutagenic processes.

Ethidium↗