Photonics: transparency on an optical chip.
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Biomedical subjects
Daniel J Gauthier
Publications and source records attributed to Daniel J Gauthier.
Direct observation of optical precursors in a region of anomalous dispersion.
We create optical precursors by propagating a step-modulated optical pulse through a linear resonant dielectric absorber. The field emerging from the dielectric consists of a several-nanosecond-long spike with near 100% transmission, which decays to a constant value expected from Beer's law. This high-transmission spike might be useful for imaging applications requiring penetrating optical radiation. We compare our observations to two different theories, revealing that the spike consists of both the Sommerfeld and Brillouin precursors.
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Single amino acid substitution in the PC1/3 propeptide can induce significant modifications of its inhibitory profile toward its cognate enzyme.
The proprotein convertase PC1/3 is synthesized as a large precursor that undergoes proteolytic processing of the signal peptide, the propeptide and ultimately the COOH-terminal tail, to generate the mature form. The propeptide is essential for protease folding, and, although cleaved by an autocatalytic process, it remains associated with the mature form acting as an auto-inhibitor of PC1/3. To further assess the role of certain residues in its interaction with its cognate enzyme, we performed an alanine scan on two PC1/3 propeptide potential cleavable sites ((50)RRSRR(54) and (61)KR(62)) and an acidic region (65)DDD(67) conserved among species. Upon incubation with PC1/3, the ensuing peptides exhibit equal inhibitory potency, lower potency, or higher potency than the wild-type propeptide. The K(i) values calculated varied between 0.15 and 16.5 nm. All but one mutant exhibited a tight binding behavior. To examine the specificity of mutants, we studied their reactivity toward furin, a closely related convertase. The mutation of certain residues also affects the inhibition behavior toward furin yielding propeptides exhibiting K(i) ranging from 0.2 to 24 nm. Mutant propeptides exhibited against each enzyme either different mode of inhibition, enhanced selectivity in the order of 40-fold for one enzyme, or high potency with no discrimination. Hence, we demonstrate through single amino acid substitution that it is feasible to modify the inhibitory behavior of propeptides toward convertases in such a way as to increase or decrease their potency, modify their inhibitory mechanisms, as well as increase their selectivity.
Amino Acid Sequence↗
Ultra-high-frequency chaos in a time-delay electronic device with band-limited feedback.
We report an experimental study of ultra-high-frequency chaotic dynamics generated in a delay-dynamical electronic device. It consists of a transistor-based nonlinearity, commercially-available amplifiers, and a transmission-line for feedback. The feedback is band-limited, allowing tuning of the characteristic time-scales of both the periodic and high-dimensional chaotic oscillations that can be generated with the device. As an example, periodic oscillations ranging from 48 to 913 MHz are demonstrated. We develop a model and use it to compare the experimentally observed Hopf bifurcation of the steady-state to existing theory [Illing and Gauthier, Physica D 210, 180 (2005)]. We find good quantitative agreement of the predicted and the measured bifurcation threshold, bifurcation type and oscillation frequency. Numerical integration of the model yields quasiperiodic and high dimensional chaotic solutions (Lyapunov dimension approximately 13), which match qualitatively the observed device dynamics.
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All-optical switching in rubidium vapor.
We report on an all-optical switch that operates at low light levels. It consists of laser beams counterpropagating through a warm rubidium vapor that induce an off-axis optical pattern. A switching laser beam causes this pattern to rotate even when the power in the switching beam is much lower than the power in the pattern. The observed switching energy density is very low, suggesting that the switch might operate at the single-photon level with system optimization. This approach opens the possibility of realizing a single-photon switch for quantum information networks and for improving transparent optical telecommunication networks.
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Tunable all-optical delays via Brillouin slow light in an optical fiber.
We demonstrate a technique for generating tunable all-optical delays in room temperature single-mode optical fibers at telecommunication wavelengths using the stimulated Brillouin scattering process. This technique makes use of the rapid variation of the refractive index that occurs in the vicinity of the Brillouin gain feature. The wavelength at which the induced delay occurs is broadly tunable by controlling the wavelength of the laser pumping the process, and the magnitude of the delay can be tuned continuously by as much as 25 ns by adjusting the intensity of the pump field. The technique can be applied to pulses as short as 15 ns. This scheme represents an important first step towards implementing slow-light techniques for various applications including buffering in telecommunication systems.
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Fast causal information transmission in a medium with a slow group velocity.
It is widely believed that the velocity of information upsiloni encoded on an optical pulse is equal to the group velocity upsilong, at least when upsilong is less than the speed of light in vacuum c. On the other hand, several authors suggest that upsiloni=c, although the size of the signal traveling at this velocity may be small, thereby making it difficult to measure. Here, we measure upsiloni for pulses propagating through a resonant "slow-light" medium where upsilong approximately 0.006c. We find upsiloni=1.03c(+0.49c)-0.25c, or that upsiloni approximately 168upsilong, clearly demonstrating that the speed of information cannot be generally described by upsilong, but is characterized by its own velocity.
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Restitution in mapping models with an arbitrary amount of memory.
Restitution, the characteristic shortening of action potential duration (APD) with increased heart rate, has been studied extensively because of its purported link to the onset of fibrillation. Restitution is often represented in the form of mapping models where APD is a function of previous diastolic intervals (DIs) and/or APDs, A(n+1)=F(D(n),A(n),D(n-1),A(n-1),...), where A(n+1) is the APD following a DI given by D(n). The number of variables previous to D(n) determines the degree of memory in the mapping model. Recent experiments have shown that mapping models should contain at least three variables (D(n),A(n),D(n-1)) to reproduce a restitution portrait (RP) that is qualitatively similar to that seen experimentally, where the RP shows three different types of restitution curves (RCs) [dynamic, S1-S2, and constant-basic cycle length (BCL)] simultaneously. However, an interpretation of the different RCs has only been presented in detail for mapping models of one and two variables. Here we present an analysis of the different RCs in the RP for mapping models with an arbitrary amount of memory. We determine the number of variables necessary to represent the different RCs in the RP. We also present a graphical visualization of these RCs. Our analysis reveals that the dynamic and S1-S2 RCs reside on two-dimensional surfaces, and therefore provide limited information for mapping models with more than two variables. However, constant-BCL restitution is a feature of the RP that depends on higher dimensions and can possibly be used to determine a lower bound on the dimensionality of cardiac dynamics.
Action Potentials↗
Rate-dependent propagation of cardiac action potentials in a one-dimensional fiber.
Action potential duration (APD) restitution, which relates APD to the preceding diastolic interval (DI), is a useful tool for predicting the onset of abnormal cardiac rhythms. However, it is known that different pacing protocols lead to different APD restitution curves (RCs). This phenomenon, known as APD rate dependence, is a consequence of memory in the tissue. In addition to APD restitution, conduction velocity restitution also plays an important role in the spatiotemporal dynamics of cardiac tissue. We present results concerning rate-dependent restitution in the velocity of propagating action potentials in a one-dimensional fiber. Our numerical simulations show that, independent of the amount of memory in the tissue, the wave-back velocity exhibits pronounced rate dependence and the wave-front velocity does not. Moreover, the discrepancy between wave-back velocity RCs is most significant for a small DI. We provide an analytical explanation of these results, using a system of coupled maps to relate the wave-front and wave-back velocities. Our calculations show that rate-dependent wave-back velocity can be present even if neither APD nor wave-front velocity exhibits rate dependence.
Action Potentials↗
Controlling fast chaos in delay dynamical systems.
We introduce a novel approach for controlling fast chaos in time-delay dynamical systems and use it to control a chaotic photonic device with a characteristic time scale of approximately 12 ns. Our approach is a prescription for how to implement existing chaos-control algorithms in a way that exploits the system's inherent time delay and allows control even in the presence of substantial control-loop latency (the finite time it takes signals to propagate through the components in the controller). This research paves the way for applications exploiting fast control of chaos, such as chaos-based communication schemes and stabilizing the behavior of ultrafast lasers.
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Condition for alternans and its control in a two-dimensional mapping model of paced cardiac dynamics.
We investigate a two-dimensional mapping model of a paced, isolated cardiac cell that relates the duration of the action potential to the two preceding diastolic intervals as well as the preceding action potential duration. The model displays rate-dependent restitution and hence memory. We derive a criterion for the stability of the 1:1 response pattern displayed by the model. This criterion can be written in terms of experimentally measured quantities-the slopes of restitution curves obtained via different pacing protocols. In addition, we analyze the two-dimensional mapping model in the presence of closed-loop feedback control. The control is initiated by making small adjustments to the pacing interval in order to suppress alternans and stabilize the 1:1 pattern. We find that the domain of control does not depend on the functional form of the map, and, in the general case, is characterized by a combination of the slopes. We show that the gain gamma necessary to establish control may vary significantly depending on the value of the slope of the so-called standard restitution curve (herein denoted as S12), but that the product gammaS12 stays approximately in the same range.
Action Potentials↗
Utilization of a new biotinylation reagent in the development of a nondiscriminatory investigative approach for the study of cell surface proteins.
In order to circumvent the various problems encountered during the study of membrane-bound proteins, we designed and synthesized a novel membrane-impermeable biotinylation reagent incorporating chemical properties compatible with this goal. We then developed a nondiscriminatory analytical procedure for such studies which overcomes possible selectivity, contamination and solubility problems. The necessary steps (labeling, limited in situ proteolysis, affinity purification) are all conducted in mild or near native conditions. This versatile method could provide an accurate picture of the cell surface proteome.
Animals↗
Improved PC1/3 production through recombinant expression in insect cells and larvae.
Protein convertase 1/3 is a serine endoproteinase present in the regulated secretory pathway of endocrine and neuroendocrine cells. It is responsible for the processing of numerous prohormones and proneuropeptides into their biologically active moieties, often following cleavage at pairs of basic residues. The determination of its three-dimensional structure, as well as the understanding of its enzymatic properties, would greatly benefit from the production and availability of large amounts of recombinant enzyme. We report herein improvements in the production of PC1/3 by expressing recombinant mutated forms in both insect cells (Spodoptera frugiperda, Sf9 cells) and larvae (Trichoplusia ni commonly referred to as cabbage looper). On one hand, we deleted the last 135 COOH-terminal residues of mPC1/3 and, on the other hand, we replaced the signal peptide of mPC1/3 by the viral glycoprotein gp67 signal peptide. These modifications were shown to improve markedly (up to 125%) the secretion into the Sf9 cells medium and the amount of enzymatic activity recovered when compared to the original vector. Moreover, intracoelemic injection of the vectors into insect larvae led to the production and purification of enzymatically active enzyme at a level of 30 microg/larva in the case of mPC1/3 and to the production of a high amount of another enzymatically active convertase, PC7. The optimal viral titer for infection of larvae was determined to be 10(6)pfu/ml. Taking into account the purification protocol combined with the ease and efficiency of using larvae, it should now be possible to meet the needs for biochemical and structural studies.
Animals↗
The restitution portrait: a new method for investigating rate-dependent restitution.
INTRODUCTION: Electrical restitution, relating action potential duration (APD) to diastolic interval (DI), was believed to determine the stability of heart rhythm. However, recent studies demonstrate that stability also depends on long-term APD changes caused by memory. This study presents a new method for investigation of rate- and memory-dependent aspects of restitution and for assessment of mapping models of APD. METHODS AND RESULTS: Bullfrog ventricular myocardium was paced with a "perturbed downsweep protocol." Starting from a basic cycle length (BCL) of 1,000 ms, the tissue was paced until steady state was achieved, followed by single beats of longer and shorter cycle lengths. BCL was decreased by 50 to 100 ms and the process repeated. All APDs were plotted as a function of the preceding DI, which allowed simultaneous observation of dynamic, S1-S2, and two constant-BCL restitution curves in a "restitution portrait." Responses were classified as 1:1 (stimulus:response), transient 2:2, or persistent 2:2 (alternans) and were related to the slopes of the restitution curves. None of these slopes approached unity for the persistent 2:2 response, demonstrating that the traditional restitution condition does not predict alternans. The restitution portrait was used to evaluate three mapping models of APD. The models with no memory and with one-beat memory did not produce restitution portraits similar to the experimental one. A model with two-beat memory produced a qualitatively similar portrait. CONCLUSION: The restitution portrait allows a more comprehensive assessment of cardiac dynamics than methods used to date. Further study of models with memory may result in a clinical criterion for electrical instability.
Action Potentials↗
The speed of information in a 'fast-light' optical medium.
One consequence of the special theory of relativity is that no signal can cause an effect outside the source light cone, the space-time surface on which light rays emanate from the source. Violation of this principle of relativistic causality leads to paradoxes, such as that of an effect preceding its cause. Recent experiments on optical pulse propagation in so-called 'fast-light' media--which are characterized by a wave group velocity upsilon(g) exceeding the vacuum speed of light c or taking on negative values--have led to renewed debate about the definition of the information velocity upsilon(i). One view is that upsilon(i) = upsilon(g) (ref. 4), which would violate causality, while another is that upsilon(i) = c in all situations, which would preserve causality. Here we find that the time to detect information propagating through a fast-light medium is slightly longer than the time required to detect the same information travelling through a vacuum, even though upsilon(g) in the medium vastly exceeds c. Our observations are therefore consistent with relativistic causality and help to resolve the controversies surrounding superluminal pulse propagation.
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Condition for alternans and stability of the 1:1 response pattern in a "memory" model of paced cardiac dynamics.
We analyze a mathematical model of paced cardiac muscle consisting of a map relating the duration of an action potential to the preceding diastolic interval as well as the preceding action potential duration, thereby containing some degree of "memory." The model displays rate-dependent restitution so that the dynamic and S1-S2 restitution curves are different, a manifestation of memory in the model. We derive a criterion for the stability of the 1:1 response pattern displayed by this model. It is found that the stability criterion depends on the slope of both the dynamic and S1-S2 restitution curves, and that the pattern can be stable even when the individual slopes are greater or less than one. We discuss the relation between the stability criterion and the slope of the constant-BCL restitution curve. The criterion can also be used to determine the bifurcation from the 1:1 response pattern to alternans. We demonstrate that the criterion can be evaluated readily in experiments using a simple pacing protocol, thus establishing a method for determining whether actual myocardium is accurately described by such a mapping model. We illustrate our results by considering a specific map recently derived from a three-current membrane model and find that the stability of the 1:1 pattern is accurately described by our criterion. In addition, a numerical experiment is performed using the three-current model to illustrate the application of the pacing protocol and the evaluation of the criterion.
Action Potentials↗
Experimental control of cardiac muscle alternans.
We demonstrate that alternans in small pieces of in vitro paced bullfrog (Rana Catesbeiana) myocardium can be suppressed by making minute adjustments to the pacing period in response to real time measurements of the action potential duration. Control is possible over a large range of physiological conditions over many animals and the self-referencing control protocol can automatically adjust to changes in the pacing interval. Our results suggest the feasibility of developing low-energy methods for maintaining normal cardiac function.
Action Potentials↗
Honeycomb pattern formation by laser-beam filamentation in atomic sodium vapor.
We have observed transverse pattern formation leading to highly regular structures in both the near and far fields when a near-resonant laser beam propagates without feedback through an atomic sodium vapor. One example is a regular far-field honeycomb pattern, which results from the transformation of the laser beam within the vapor into a stable three-lobed structure with a uniform phase distribution and highly correlated power fluctuations. The predictions of a theoretical model of the filamentation process are in good agreement with these observations.
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