The mechanisms of cellular crosstalk between mesenchymal stem cells and natural killer cells: Therapeutic implications.

Mesenchymal stem cells (MSCs) are mesenchymal precursors of various origins, with well-known immunomodulatory effects. Natural killer (NK) cells, the major cells of the innate immune system, are critical for the antitumor and antiviral defenses; however, in certain cases, they may be the main culprits in the pathogenesis of some NK-related conditions such as autoimmunities and hematological malignancies. On the other hand, these cells seem to be the major responders in beneficial phenomena like graft versus leukemia. Substantial data suggest that MSCs can variably affect NK cells and can be affected by these cells. Accordingly, acquiring a profound understanding of the crosstalk between MSCs and NK cells and the involved mechanisms seems to be a necessity to develop therapeutic approaches based on such interactions. Therefore, in this study, we made a thorough review of the existing literature on the interactions between MSCs and NK cells with a focus on the underlying mechanisms. The current knowledge herein suggests that MSCs possess a great potential to be used as tools for therapeutic targeting of NK cells in disease context and that preconditioning of MSCs, as well as their genetic manipulation before administration, may provide a wider variety of options in terms of eliciting more specific and desirable therapeutic outcomes. Nevertheless, our knowledge regarding the effects of MSCs on NK cells is still in its infancy, and further studies with well-defined conditions are warranted herein.

Anamorphic transformation and its application to time-bandwidth compression.

A general method for compressing the modulation time-bandwidth product of analog signals is introduced. As one of its applications, this physics-based signal grooming, performed in the analog domain, allows a conventional digitizer to sample and digitize the analog signal with variable resolution. The net result is that frequency components that were beyond the digitizer bandwidth can now be captured and, at the same time, the total digital data size is reduced. This compression is lossless and is achieved through a feature selective reshaping of the signal's complex field, performed in the analog domain prior to sampling. Our method is inspired by operation of Fovea centralis in the human eye and by anamorphic transformation in visual arts. The proposed transform can also be performed in the digital domain as a data compression algorithm to alleviate the storage and transmission bottlenecks associated with "big data."

Self-referenced temporal phase reconstruction from intensity measurements using causality arguments in linear optical filters.

We introduce and numerically demonstrate a simple and general concept for direct reconstruction of the temporal phase profile of an optical signal from temporal intensity measurements at the input and output of an arbitrary linear optical filter. The concept is based on exploiting the linearity and causality properties of any physical filter. Very few restrictions need to be imposed on the optical filter response to ensure an unambiguous phase reconstruction. The filter can be specifically designed to minimize the noise influence on the measurement process.

New design for photonic temporal integration with combined high processing speed and long operation time window.

We propose and experimentally prove a novel design for implementing photonic temporal integrators simultaneously offering a high processing bandwidth and a long operation time window, namely a large time-bandwidth product. The proposed scheme is based on concatenating in series a time-limited ultrafast photonic temporal integrator, e.g. implemented using a fiber Bragg grating (FBG), with a discrete-time (bandwidth limited) optical integrator, e.g. implemented using an optical resonant cavity. This design combines the advantages of these two previously demonstrated photonic integrator solutions, providing a processing speed as high as that of the time-limited ultrafast integrator and an operation time window fixed by the discrete-time integrator. Proof-of-concept experiments are reported using a uniform fiber Bragg grating (as the original time-limited integrator) connected in series with a bulk-optics coherent interferometers' system (as a passive 4-points discrete-time photonic temporal integrator). Using this setup, we demonstrate accurate temporal integration of complex-field optical signals with time-features as fast as ~6 ps, only limited by the processing bandwidth of the FBG integrator, over time durations as long as ~200 ps, which represents a 4-fold improvement over the operation time window (~50 ps) of the original FBG integrator.

Photonic temporal integration of broadband intensity waveforms over long operation time windows.

We propose and experimentally demonstrate a novel design for temporal integration of microwave and optical intensity waveforms with combined high processing speed and a long operation time window. It is based on concatenating in series a discrete-time (low-speed) photonic integrator and a high-speed analog time-limited intensity integrator. This scheme is demonstrated here using a cascaded fiber-based interferometers' system (as a passive eight-point discrete-time integrator) and an analog time-limited intensity integrator. The latter is based on temporal intensity modulation of the input waveform with a rectangular-like incoherent energy spectrum followed by linear dispersion. Using this setup, we experimentally achieve accurate time integration of intensity signals with ~36 GHz bandwidths over an operation time window of ~4 ns, corresponding to a processing time-bandwidth product of >144.

Complex-field measurement of ultrafast dynamic optical waveforms based on real-time spectral interferometry.

Several methods are now available for single-shot measurement of the complex field (amplitude and phase profiles) of optical waveforms with resolutions down to the sub-picosecond range. As a main critical limitation, all these techniques exhibit measurement update rates typically slower than a few Hz. It would be very challenging to directly upgrade the update rate of any of these available methods beyond a few kHz. By combining spectral interferometry with dispersion-induced real-time optical Fourier transformation, here we demonstrate single-shot complex-field measurements of optical waveforms with a resolution of approximately 400 fs over a record length as long as approximately 350 ps, corresponding to a large record-length-to-resolution ratio of approximately 900. This performance is achieved at a measurement update rate of approximately 17 MHz, i.e. at least one thousand times faster than with any previous single-shot complex-field THz-bandwidth optical signal characterization method.

High-order passive photonic temporal integrators.

We experimentally demonstrate, for the first time to our knowledge, an ultrafast photonic high-order (second-order) complex-field temporal integrator. The demonstrated device uses a single apodized uniform-period fiber Bragg grating (FBG), and it is based on a general FBG design approach for implementing optimized arbitrary-order photonic passive temporal integrators. Using this same design approach, we also fabricate and test a first-order passive temporal integrator offering an energetic-efficiency improvement of more than 1 order of magnitude as compared with previously reported passive first-order temporal integrators. Accurate and efficient first- and second-order temporal integrations of ultrafast complex-field optical signals (with temporal features as fast as approximately 2.5ps) are successfully demonstrated using the fabricated FBG devices.

Design of all-optical high-order temporal integrators based on multiple-phase-shifted Bragg gratings.

In exact analogy with their electronic counterparts, photonic temporal integrators are fundamental building blocks for constructing all-optical circuits for ultrafast information processing and computing. In this work, we introduce a simple and general approach for realizing all-optical arbitrary-order temporal integrators. We demonstrate that the N(th) cumulative time integral of the complex field envelope of an input optical waveform can be obtained by simply propagating this waveform through a single uniform fiber/waveguide Bragg grating (BG) incorporating N pi-phase shifts along its axial profile. We derive here the design specifications of photonic integrators based on multiple-phase-shifted BGs. We show that the phase shifts in the BG structure can be arbitrarily located along the grating length provided that each uniform grating section (sections separated by the phase shifts) is sufficiently long so that its associated peak reflectivity reaches nearly 100%. The resulting designs are demonstrated by numerical simulations assuming all-fiber implementations. Our simulations show that the proposed approach can provide optical operation bandwidths in the tens-of-GHz regime using readily feasible photo-induced fiber BG structures.

Transform-limited picosecond pulse shaping based on temporal coherence synthesization.

A simple and efficient optical pulse re-shaper based on the concept of temporal coherence synthesization is proposed and analyzed in detail. Specifically, we demonstrate that an arbitrary chirp-free (transform-limited) optical pulse waveform can be synthesized from a given transform-limited Gaussian-like input optical pulse by coherently superposing a set of properly delayed replicas of this input pulse, e.g. using a conventional multi-arm interferometer. A practical implementation of this general concept based on the use of conventional concatenated two-arm interferometers is also suggested and demonstrated. This specific implementation allows the synthesis of any desired temporally-symmetric optical waveform with time features only limited by the input pulse bandwidth. A general optimization algorithm has been developed and applied for designing the system specifications (number of interferometers and relative time delays in these interferometers) that are required to achieve a desired optical pulse re-shaping operation. The required tolerances in this system have been also estimated and confirmed by numerical simulations. The proposed technique has been experimentally demonstrated by re-shaping an approximately 1-ps Gaussian-like optical pulse into various temporal shapes of practical interest, i.e. picosecond transform-limited flat-top, parabolic and triangular pulses (all centered at a wavelength of approximately 1550nm), using a simple two-stage interferometer setup. A remarkable synthesis accuracy and high energetic efficiency have been achieved for all these pulse re-shaping operations.

Phase stretch transform for super-resolution localization microscopy.

Super-resolution localization microscopy has revolutionized the observation of living structures at the cellular scale, by achieving a spatial resolution that is improved by more than an order of magnitude compared to the diffraction limit. These methods localize single events from isolated sources in repeated cycles in order to achieve super-resolution. The requirement for sparse distribution of simultaneously activated sources in the field of view dictates the acquisition of thousands of frames in order to construct the full super-resolution image. As a result, these methods have slow temporal resolution which is a major limitation when investigating live-cell dynamics. In this paper we present the use of a phase stretch transform for high-density super-resolution localization microscopy. This is a nonlinear frequency dependent transform that emulates the propagation of light through a physical medium with a specific warped diffractive property and applies a 2D phase function to the image in the frequency domain. By choosing properly the transform parameters and the phase kernel profile, the point spread function of each emitter can be sharpened and narrowed. This enables the localization of overlapping emitters, thus allowing a higher density of activated emitters as well as shorter data collection acquisition rates. The method is validated by numerical simulations and by experimental data obtained using a microtubule sample.

Edge detection in digital images using dispersive phase stretch transform.

We describe a new computational approach to edge detection and its application to biomedical images. Our digital algorithm transforms the image by emulating the propagation of light through a physical medium with specific warped diffractive property. We show that the output phase of the transform reveals transitions in image intensity and can be used for edge detection.

All-optical Hilbert transformer based on a single phase-shifted fiber Bragg grating: design and analysis.

A simple all-fiber design for implementing an all-optical temporal Hilbert transformer is proposed and numerically demonstrated. We show that an all-optical Hilbert transformer can be implemented using a uniform-period fiber Bragg grating (FBG) with a properly designed amplitude-only grating apodization profile incorporating a single pi phase shift in the middle of the grating length. All-optical Hilbert transformers capable of processing arbitrary optical waveforms with bandwidths up to a few hundreds of gigahertz can be implemented using feasible FBGs.

Proposal for arbitrary-order temporal integration of ultrafast optical signals using a single uniform-period fiber Bragg grating.

A simple and practical all-fiber design for implementing arbitrary-order temporal integration of ultrafast optical waveforms is proposed and numerically investigated. We demonstrate that an ultrafast photonics integrator of any desired integration order can be implemented using a uniform-period fiber Bragg grating (FBG) with a properly designed amplitude-only grating apodization profile. In particular, the grating coupling strength must vary according to the (N-1) power of the fiber distance for implementing an Nth-order photonics integrator (N=1,2,...). This approach requires the same level of practical difficulty for realizing any given integration order. The proposed integration devices operate over a limited time window, which is approximately fixed by the round-trip propagation time in the FBG. Ultrafast arbitrary-order all-optical integrators capable of accurate operation over nanosecond time windows can be implemented using readily feasible FBGs.