Cognitive impairment in temporal lobe epilepsy: role of online and offline processing of single cell information.

Cognitive impairment is a common comorbidity in temporal lobe epilepsy (TLE) and is often considered more detrimental to quality of life than seizures. While it has been previously shown that the encoding of memory during behavior is impaired in the pilocarpine model of TLE in rats, how this information is consolidated during the subsequent sleep period remains unknown. In this study, we first report marked deficits in spatial memory performance and severe cell loss in the CA1 layer of the hippocampus lower spatial coherence of firing in TLE rats. We then present the first evidence that the reactivation of behavior-driven patterns of activity of CA1 place cells in the hippocampus is intact in TLE rats. Using a template-matching method, we discovered that real-time (3-5 s) reactivation structure was intact in TLE rats. Furthermore, we estimated the entropy rate of short time scale (∼250 ms) bursting activity using block entropies and found that significant, extended temporal correlations exist in both TLE and control rats. Fitting a first-order Markov Chain model to these bursting time series, we found that long sequences derived from behavior were significantly enriched in the Markov model over corresponding models fit on randomized data confirming the presence of replay in shorter time scales. We propose that the persistent consolidation of poor spatial information in both real time and during bursting activity may contribute to memory impairments in TLE rats.

Photoconductive optically driven deformable membrane under high-frequency bias: fabrication, characterization, and modeling.

The fabrication and characterization of an optically addressable deformable mirror for a spatial light modulator are described. Device operation utilizes an electrostatically driven pixelated aluminized polymeric membrane mirror supported above an optically controlled photoconductive GaAs substrate. A 5 mum thick grid of patterned photoresist supports the 2 mum thick aluminized Mylar membrane. A conductive ZnO layer is placed on the backside of the GaAs wafer. Similar devices were also fabricated with InP. A standard Michelson interferometer is used to measure mirror deformation data as a function of illumination, applied voltage, and frequency. The device operates as an impedance distribution between two cascaded impedances of deformable membrane substrate, substrate, and electrode. An analysis of device's operation under several bias conditions, which relates membrane deformation to operating parameters, is presented.

Real-time holographic deconvolution techniques for one-way image transmission through an aberrating medium: characterization, modeling, and measurements.

We propose and demonstrate a new photorefractive real-time holographic deconvolution technique for adaptive one-way image transmission through aberrating media by means of four-wave mixing. In contrast with earlier methods, which typically required various codings of the exact phase or two-way image transmission for correcting phase distortion, our technique relies on one-way image transmission through the use of exact phase information. Our technique can simultaneously correct both amplitude and phase distortions. We include several forms of image degradation, various test cases, and experimental results. We characterize the performance as a function of the input beam ratios for four metrics: signal-to-noise ratio, normalized root-mean-square error, edge restoration, and peak-to-total energy ratio. In our characterization we use false-color graphic images to display the best beam-intensity ratio two-dimensional region(s) for each of these metrics. Test cases are simulated at the optimal values of the beam-intensity ratios. We demonstrate our results through both experiment and computer simulation.

Inverse scattering method applied to the synthesis of strongly scattering structures.

A nonlinear signal processing method based on cepstral filtering has been developed to provide an approximate solution to the inverse scattering problem in two dimensions. It has been used to recover images of strongly scattering objects from measured far-field scattering data and is applied here to synthesize structures with prescribed scattering characteristics. An example is shown to illustrate the synthesis method. The scattering properties of the resulting structures are verified using a finite difference time domain method. The inverse scattering method is straightforward to implement and requires reprocessing of the scattered field data in order to ensure that the function describing the secondary source (contrast source function) has the properties of being a minimum phase function. This is accomplished by a numerical preprocessing step involving an artificial reference wave.

A model for switch-like phenomena in biological systems.

We present a model for the activity of protein clusters based on a simultaneous desorption of an activator (agonist, substrate molecule, etc.) and an inactivator (antagonist, inhibitor, etc.) caused by the collision or interaction between two effector molecules (e.g. receptors, enzymes). This model gives rise to switch-like dose-response curves, which are difficult to explain by ordinary co-operativity. It fits with recent experimental results obtained on single cells. Some other interesting aspects of the model are also pointed out. The model is similar to the model used to explain steep 'dose-response curves' in heterogeneous catalysis, caused by the reaction between two different molecules or atoms on the surface of the catalyst.

Characterization of [3H]flunitrazepam binding to melanin.

In both clinical and forensic toxicology, the analysis of hair for drugs is an important tool to determine drug use in the past or to verify abstinence from illegal drugs during extended periods. Melanin is proposed as one of the factors that influences drug incorporation to hair and we have characterized the binding of the drug flunitrazepam to melanin in vitro. The drug was 3H labeled and melanin granules from cuttlefish, Sepia officinalis, were used according to the suggested standard for melanin studies. We observed a rapid Langmuir-like binding followed by a slower diffusion-limited binding that may be interpreted as an initial surface binding followed by deeper bulk binding. From three concentrations of melanin, with a 60-min incubation time, a mean saturation value of 180 +/- 20 pmol/mg was calculated. The binding of a group of benzodiazepines and tranquilizers was compared to the binding of [3H]flunitrazepam by means of displacement experiments. These drugs showed binding characteristics similar to [3H]flunitrazepam except phenobarbital, which had a lower affinity to melanin. The method presented in this study allowed measurements with low melanin and drug concentrations and it has the strength of directly measuring the amount of drug bound to melanin, in contrast to previous indirect methods.

Efficient optimization of diffractive optical elements based on rigorous diffraction models.

An efficient optimization strategy for the design of diffractive optical elements that is based on rigorous diffraction theory is described. The optimization algorithm combines diffraction models of different degrees of accuracy and computational complexity. A fast design algorithm for diffractive optical elements is used to yield estimates of the optimum surface profile based on paraxial diffraction theory. These estimates are subsequently evaluated with a rigorous diffraction model. This scheme allows one to minimize the need to compute diffraction effects rigorously, while providing accurate design. We discuss potential applications of this scheme as well as details of an implementation based on a modified Gerchberg-Saxton algorithm and the finite-difference time-domain method. Illustrative examples are provided in which we use the algorithm to design Fourier array illuminators.

The electric charge of pigment granules in pigment cells.

Black pigment cells called melanophores change colour in response to environmental changes and have lately been studied as promising biosensors. To further elucidate the intracellular processes involved in the colour changes of these cells, and to find optimal biosensing principles, the electric charge of intracellular pigment granules, melanosomes, has been determined in vitro by electrophoresis. Melanosomes from the two extreme states in the cell colour change (aggregated and dispersed melanosomes) were measured. The charge was found to be -1.5 x 10(-16) and -1.7 x 10(-16) C, aggregated and dispersed melanosomes, respectively, without significant difference between the two conditions. This charge is of the same order of magnitude as the one of 1000 electrons. The origin of the melanosome charge, and the use of these findings in new biosensor principles, is discussed.

Volume changes of individual melanosomes measured by scanning force microscopy.

Black pigment cells, melanophores, e.g. located in the epidermis and dermis of frogs, are large flat cells having intracellular black pigment granules, called melanosomes. Due to a large size, high optical contrast, and quick response to drugs, melanophores are attractive as biosensors as well as for model studies of intracellular processes; e.g. organelle transport and G-protein coupled receptors. The geometry of melanosomes from African clawed toad, Xenopus laevis, has been measured using scanning force microscopy (SFM). Three-dimensional images from SFM were used to measure height, width, and length of the melanosomes (100 from aggregated cells and 100 from dispersed cells). The volumes of melanosomes isolated from aggregated and dispersed melanophores were significantly different (P < 0.05, n=200). The average ellipsoidal volume was 0.14+/-0.01 (aggregated) and 0.17+/-0.01 microm3 (dispersed), a difference of 18%. The average major diameter was 810+/-20 and 880+/-20 nm for aggregated and dispersed melanosomes, respectively. To our knowledge, this is the first time SFM has been used to study melanosomes. This may provide an alternative non-destructive technique that may be particularly suitable for studying morphological aspects of various melanin granules.

On the zero-thickness model of diffractive optical elements

In a recent paper [J. Opt. Soc. Am. A 16, 113 (1999)] a thin-element approximation of diffractive optical elements was used to describe diffraction of oblique incident wave fronts. This expression motivated by a ray optical analysis is shown to be incorrect. I discuss how the thin-element approximation can be generalized to arbitrary diffraction geometries. This includes an intuitive interpretation of the results.

Iterative optimization of phase-only diffractive optical elements based on a lenslet array.

We describe the design of Fourier-type phase-only array generators. The numerical optimization employs the Fienup algorithm, where the parageometric design of the phase retardation profile, with the form of a lenslet array, is used as the initial guess of the optimization process. This approach provides designs with high performance that can be obtained with comparatively low computing effort. This is particularly true for elements generating large spot arrays. For symmetric reconstruction fields, the optimized phase profile typically has the same symmetry as that for the reconstruction field and can be easily unwrapped.

Analysis of the moiré effect by use of the Wigner distribution function.

The Wigner distribution function is used to analyze moiré patterns that originate from a superposition of nonperiodic masks. For patterns with well-defined local frequencies, the concept of the Wigner distribution function allows one to extend the description of the moiré effect in terms of vector sums. How this picture can be applied to design moiré patterns and to analyze their information content is also discussed.

Sampling of time- and frequency-domain signals in monte carlo simulations of photon migration.

We compare two fundamentally different ways to evaluate the time dependence in Monte Carlo simulations of photon migration: estimating the pulse response in time versus evaluating the transfer function at discrete points in the frequency domain. We show that these two methods differ in accuracy owing to quantization and sampling errors, whereas the statistical error is essentially the same for both methods. From our analysis we also derive alternative methods to sample the time-domain pulse response with reduced quantization and sampling error. Simulation results are included to illustrate our theoretical analysis.

Planar-integrated talbot array illuminators.

We demonstrate the planar integration of Talbot array illuminators designed to generate one-dimensional spot arrays. The array illuminator basically consists of a phase grating and a cylindrical diffractive lens integrated as a single diffractive optical element onto a transparent glass substrate. We discuss various design aspects, and we focus on problems typical for planar-integrated free-space optics like the tilted optical axis of the system. Experimental results and measurements, which were obtained from planar-integrated setups fabricated as surface-relief structures on a transparent glass substrate by use of standard photolithography, are included.

Efficiency limit of spatially quantized Fourier array illuminators.

We derive an upper limit for the efficiency of spatially quantized Fourier array illuminators. This complements a previously reported formula for the efficiency limit of diffractive elements constrained only in phase.

Instrumentation and design of a frequency-domain diffuse optical tomography imager for breast cancer detection.

The instrument development and design of a prototype frequency-domain optical imaging device for breast cancer detection is described in detail. This device employs radio-frequency intensity modulated near-infrared light to image quantitatively both the scattering and absorption coefficients of tissue. The functioning components of the system include a laser diode and a photomultiplier tube, which are multiplexed automatically through 32 large core fiber optic bundles using high precision linear translation stages. Image reconstruction is based on a finite element solution of the diffusion equation. This tool for solving the forward problem of photon migration is coupled to an iterative optical property estimation algorithm, which uses a Levenberg-Marquardt routine with total variation minimization. The result of this development is an automated frequency-domain optical imager for computed tomography which produces quantitatively accurate images of the test phantoms used to date. This paper is a description and characterization of an automated frequency-domain computed tomography scanner, which is more quantitative than earlier systems used in diaphanography because of the combination of intensity modulated signal detection and iterative image reconstruction.

Gradient-index microlenses: numerical investigation of different spherical index profiles with the wave propagation method.

Ion-exchange microlenses are available with different gradient-index profiles. We investigate the dependence of the imaging properties on the steepness of the index profiles. Therefore we model the index distribution by the Fermi function as radial distribution with spherical symmetry. The results are compared to index profiles according to the Doremus model.

Transition between diffractive and refractive micro-optical components.

Optical components are usually classified into diffractive and refractive elements. In this classification, refractive components are defined as elements that are sufficiently described by geometrical optics. For micro-optics this distinction is very often not applicable. Our goal is to understand which parameters control the transition from elements that can be interpreted as refractive to those elements that are called diffractive. We investigate the linear blazed grating and focus on the wavelength dependence of its properties. For this we adopt an approach well known from the theory of echelette gratings. Our results can easily be transferred to other blazed components, such as Fresnel lenses.

Evaluation of microlens properties in the presence of high spherical aberration.

Microlenses can be generated with various fabrication technologies. Some of these technologies cause large spherical aberrations in the resulting microlenses. We describe an algorithm based on Rayleigh's quarter-wave criterion, which allows the evaluation of lens parameters for those microlenses. Specifically, we investigate numerical aperture, focal length, and space-bandwidth product with respect to applications in optical microsystems. We apply our algorithm to different types of microlenses, three gradient-index lenses, and one surface-relief lens. The experimental results demonstrate that our algorithm provides a helpful characterization method for microlenses with large aberrations.

Astigmatic gradient-index elements for laser-diode collimation and beam shaping.

For the conversion of light from edge-emitting laser diodes into symmetric laser beams two main tasks have to be performed: collimation and beam shaping. Generally these two jobs are performed separately. Because of the inherently different divergence angles of the emitted light, collimation with astigmatic lenses generally results in a beam with an elliptically shaped amplitude distribution. This asymmetry has to be compensated for by an anamorphic imaging step to obtain the desired spherical beam profile. It can be advantageous to combine both jobs in one element. We demonstrate the design, the fabrication, and the application of refractive gradient-index elements, which allow one to perform both jobs with a single element. Our astigmatic lenses were fabricated by silver-sodium ion exchange in glass.