Modulation of Sarco/Endoplasmic Reticulum Ca2+-ATPase 2 (SERCA2) function by acetylation following the treatment with histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA)

Background: Acetylation and deacetylation at specific lysine (K) residues is mediated by histone acetylases (HATs) and deacetylases (HDACs), respectively. HATs and HDACs act on both histone and non-histone proteins, regulating various processes, including cardiac impulse propagation. Aim of the present work was to establish whether the function of the Ca2+ ATPase SERCA2, one of the major players in Ca2+ reuptake during excitation-contraction coupling in cardiac myocytes (CMs), could be modulated by direct K acetylation. Materials and methods: HL-1 atrial mouse cells (donated by Prof. Claycomb), zebrafish and Streptozotocin-induced diabetic rat CMs were treated with the pan-inhibitor of class I and II HDACs suberanilohydroxamic acid (SAHA) for 1.5 hour. Evaluation of SERCA2 acetylation was analyzed by co-immunoprecipitation. SERCA2 activity was measured on microsomes by pyruvate/NADH coupled reaction assay. SERCA2 mutants were obtained after cloning wild-type and mutated sequences into the pCDNA3 vector and transfected into HEK cells. Ca2+ transients in CMs (loading with Fluo3-AM, field stimulation, 0.5 Hz) and in transfected HEK cells (loading with FLUO-4, caffeine pulse) were recorded. Results: Co-Immunoprecipitation experiments performed on HL-1 cells demonstrated a significant increase in the acetylation of SERCA2 after SAHA-treatment (2.5 µM, n=3). This was associated with an increase in SERCA2 activity in microsomes obtained from HL-1 cells, after SAHA exposure (n=5). Accordingly, SAHA-treatment significantly shortened the Ca2+ reuptake time of adult zebrafish CMs. Further, SAHA 2.5 nM restored to control values the recovery time of Ca2+ transients decay in diabetic rat CMs. HDAC inhibition also improved contraction parameters, such as fraction of shortening, and increased pump activity in microsomes isolated from diabetic CMs (n=4). Notably, the K464, identified by bioinformatic tools as the most probable acetylation site on human SERCA2a, was mutated into Glutamine (Q) or Arginine (R) mimicking acetylation and deacetylation respectively. Measurements of Ca2+ transients in HEK cells revealed that the substitution of K464 with R significantly delayed the transient recovery time, thus indicating that deacetylation has a negative impact on SERCA2 function. Conclusions: Our results indicate that SERCA2 function can be improved by pro-acetylation interventions and that this mechanism of regulation is conserved among species. Therefore, the present work provides the basis to open the search for novel pharmacological tools able to specifically improve SERCA2 activity in diseases where its expression and/or function is impaired, such as diabetic cardiomyopathy.

Operator's and organizational maintenance manual : pulse form restorer TD-12l8/G (NSN 5820-01-145-4938).

"5 March 1985."

All-optical TDM to WDM signal conversion and partial regeneration using XPM with triangular pulses

We propose a new all-optical, all-fibre scheme for conversion of time-division multiplexed to wavelength-division multiplexed signals using cross-phase modulation with triangular pulses. Partial signal regeneration using this technique is also demonstrated.

Time-division-multiplexing using pulse position locking for 100 Gb/s applications

Recently, there is a great interest in pushing communication technologies to 100 Gb/s. However, there are still many challenges to perform high speed (> 40 Gb/s) clock and data recovery, and data time-division-multiplexing (TDM). Here, we propose and numerically analyze an asynchronous optical packet retimer using parabolic or sinusoidal phase modulation and linear dispersion. This scheme is named pulse position locking (PPL). Numerical simulation shows that this scheme can effectively resynchronize input signals with arbitrary delays to the local clock, and reduce input jitter. The scheme can also be applied to TDM 10 Gb/s and 40 Gb/s signals to over 100 Gb/s.

Generation of triangular-shaped optical pulses in normally dispersive fibre

We determine through numerical modelling the conditions for the generation of triangular-shaped optical pulses in a nonlinear, normally dispersive (ND) fibre and experimentally demonstrate triangular pulse formation in conventional ND fibre.

Nonlinear pulse shaping in fibres for pulse generation and optical processing

The development of new all-optical technologies for data processing and signal manipulation is a field of growing importance with a strong potential for numerous applications in diverse areas of modern science. Nonlinear phenomena occurring in optical fibres have many attractive features and great, but not yet fully explored, potential in signal processing. Here, we review recent progress on the use of fibre nonlinearities for the generation and shaping of optical pulses and on the applications of advanced pulse shapes in all-optical signal processing. Amongst other topics, we will discuss ultrahigh repetition rate pulse sources, the generation of parabolic shaped pulses in active and passive fibres, the generation of pulses with triangular temporal profiles, and coherent supercontinuum sources. The signal processing applications will span optical regeneration, linear distortion compensation, optical decision at the receiver in optical communication systems, spectral and temporal signal doubling, and frequency conversion. © Copyright 2012 Sonia Boscolo and Christophe Finot.

Generation of triangular pulses in normally dispersive fibre

In this scheme, nonlinearity and dispersion in the NDF lead to various reshaping processes of an initial, conventional pulse according to the chirping value and power level at the input of the fibre. In particular, we have observed that triangular-shaped pulses can be generated for sufficiently high energies and a positive initial chirp parameter. In our experiments, 2.8 ps-FWHM, transform-limited pulses generated from a mode-locked fibre laser source at a repetition rate of 1.25 GHz were pre-chirped by propagating the pulses through different lengths of standard mono-mode fibre. The chirped pulses were then amplified to different power levels before being launched into a 2.3 km section of True Wave fibre (TWF). The corresponding numerically calculated pulse temporal intensity profile and numerical and experimental second-harmonic generation frequency-resolved optical gating (SHG FROG) spectrograms were also derived. In conclusion, we have presented numerical modelling results which show the system design parameters required for the generation of triangular-shaped pulses in a nonlinear NDF, and experimentally demonstrated triangular pulse shaping in conventional NDF.

Pulse shaping in mode-locked ring-cavity fibre lasers

By means of extensive numerical modelling we have demonstrated the possibility of nonlinear pulse shaping in a mode-locked fibre laser using control of the intra-cavity propagation dynamics by adjustment of the normal net dispersion and integrated gain. Beside self-similar mode-locking, the existence of a novel type of pulse shaping regime that produces pulses with a triangular temporal intensity profile and a linear frequency chirp has been observed.

Nonlinearly generated advanced pulse waveforms for optical signal processing

Nonlinear phenomena occurring in optical fibres have many attractive features and great, but not yet fully explored potential in signal processing. Here, we review recent progress on the use of fibre nonlinearities for the generation and shaping of optical pulses, and on the applications of advanced pulse waveforms in all-optical signal processing. Among other topics, we will discuss ultrahigh repetition-rate pulse sources, the generation of parabolic-shaped pulses in active and passive fibres, the generation of pulses with triangular temporal profiles, and coherent supercontinuum sources. The signal processing applications will span optical regeneration, linear distortion compensation, optical decision at the receiver in optical communication systems, spectral and temporal signal doubling, and frequency conversion. © 2012 IEEE.

Rayleigh noise mitigation in DWDM LR-PONs using carrier suppressed subcarrier-amplitude modulated phase shift keying

We demonstrate a novel Rayleigh interferometric noise mitigation scheme for applications in carrier-distributed dense wavelength division multiplexed (DWDM) passive optical networks at 10 Gbit/s using carrier suppressed subcarrier-amplitude modulated phase shift keying modulation. The required optical signal to Rayleigh noise ratio is reduced by 12 dB, while achieving excellent tolerance to dispersion, subcarrier frequency and drive amplitude variations.

Novel real-time homodyne coherent receiver using a feed-forward based carrier extraction scheme for phase modulated signals

We report a novel real-time homodyne coherent receiver based on a DPSK optical-electrical-optical (OEO) regenerator used to extract a carrier from carrier-less phase modulated signals based on feed-forward based modulation stripping. The performance of this non-DSP based coherent receiver was evaluated for 10.66Gbit/s BPSK signals. Self-homodyne coherent detection and homodyne detection with an injection-locked local oscillator laser was demonstrated. The performance was evaluated by measuring the electrical signal-to-noise (SNR) and recording the eye diagrams. Using injection-locking for the LO improves the performance and enables homodyne detection with optical injection-locking to operate with carrier-less BPSK signals without the need for polarization multiplexed pilot-tones.

Novel synchronous DPSK optical regenerator based on a feed-forward based carrier extraction scheme

We experimentally demonstrate a novel synchronous 10.66Gbit/s DPSK OEO regenerator which uses a feed-forward carrier extraction scheme with an injection-locked laser to synchronize the regenerated signal wavelength to the incoming signal wavelength. After injection-locking, a low-cost DFB laser used at the regenerator exhibited the same linewidth characteristics as the narrow line-width transmitter laser. The phase regeneration properties of the regenerator were evaluated by emulating random Gaussian phase noise applied to the DPSK signal before the regenerator using a phase modulator driven by an arbitrary waveform generator. The overall performance was evaluated in terms of electrical eye-diagrams, BER measurements, and constellation diagrams.

Nonlinear pulse distortion in few-mode fiber

Nonlinear pulse propagation in a few mode fiber is experimentally investigated, by measuring temporal and phase responses of the output pulses by use of a frequency discriminator technique, showing that self-phase modulation, dispersion and linear mode-coupling are the dominant effects.

Graphene based widely-tunable and singly-polarized pulse generation with random fiber lasers

Pulse generation often requires a stabilized cavity and its corresponding mode structure for initial phase-locking. Contrastingly, modeless cavity-free random lasers provide new possibilities for high quantum efficiency lasing that could potentially be widely tunable spectrally and temporally. Pulse generation in random lasers, however, has remained elusive since the discovery of modeless gain lasing. Here we report coherent pulse generation with modeless random lasers based on the unique polarization selectivity and broadband saturable absorption of monolayer graphene. Simultaneous temporal compression of cavity-free pulses are observed with such a polarization modulation, along with a broadly-tunable pulsewidth across two orders of magnitude down to 900 ps, a broadly-tunable repetition rate across three orders of magnitude up to 3 MHz, and a singly-polarized pulse train at 41 dB extinction ratio, about an order of magnitude larger than conventional pulsed fiber lasers. Moreover, our graphene-based pulse formation also demonstrates robust pulse-to-pulse stability and widewavelength operation due to the cavity-less feature. Such a graphene-based architecture not only provides a tunable pulsed random laser for fiber-optic sensing, speckle-free imaging, and laser-material processing, but also a new way for the non-random CW fiber lasers to generate widely tunable and singly-polarized pulses.

Nonlinear pulse shaping and polarization dynamics in mode-locked fibre lasers

We review our recent progress on the study of new nonlinear mechanisms of pulse shaping in passively mode-locked fibre lasers. These include a mode-locking regime featuring pulses with a triangular distribution of the intensity, and spectral compression arising from nonlinear pulse propagation. We also report on our recent experimental studies unveiling new families of vector solitons with precessing states of polarization for multipulsing and bound-state soliton operations in a carbon nanotube mode-locked fibre laser with anomalous dispersion cavity. © 2013 IEEE.