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We demonstrate a new biphoton manipulation and characterization technique based on electro-optic intensity modulation and time shifting. By applying fast modulation signals with a sharply peaked cross-correlation to each photon from an entangled pair, it is possible to measure temporal correlations with significantly higher precision than that attainable using standard single-photon detection. Low-duty-cycle pulses and maximal-length sequences are considered as modulation functions, reducing the time spread in our correlation measurement by a factor of five compared to our detector jitter. With state-of-the-art electro-optic components, we expect the potential to surpass the speed of any single-photon detectors currently available.

We investigate the low timing jitter properties of a tunable single-pass optoelectronic frequency comb generator. The scheme is flexible in that both the repetition rate and center frequency can be continuously tuned. When operated with 10 GHz comb spacing, the integrated residual pulse-to-pulse timing jitter is 11.35 fs (1 Hz to 10 MHz) with no feedback stabilization. The corresponding phase noise at 1 Hz offset from the photodetected 10 GHz carrier is -100 dBc/Hz.

We propose and demonstrate a novel approach for controlling the temporal position of the biphoton correlation function using pump frequency tuning and dispersion cancellation; precise waveguide engineering enables biphoton generation at different pump frequencies while the idea of nonlocal dispersion cancellation is used to create the relative signal-idler delay and simultaneously prevents broadening of their correlation. Experimental results for delay shifts up to ±15 times the correlation width are shown along with discussions of the performance metrics of this approach.

Phase imaging microscopy, based either on holography or nonholographic methods such as phase retrieval, has seen considerable attention recently. Phase retrieval offers the advantage of being free of a reference arm and enables a more stable and compact setup. We present an optical setup that provides enhanced resolution by implementing synthetic aperture imaging based on phase retrieval using an electrically tunable lens (ETL). The ETL is a more compact and less expensive alternative to computerized translation stages and spatial light modulators. Before applying phase retrieval, we discuss a general calibration algorithm, which performs image registration, corrects for magnifications, and determines the axial locations of image planes. Finally, we obtain resolution-enhanced images of a phase grating and of cells to demonstrate the practical application of our technique.

We introduce a novel photonic-assisted ultrabroadband radio-frequency arbitrary waveform generation setup capable of high-speed phase and amplitude modulation of the individual arbitrary waveforms. The waveform generator is based on an optical interferometer, within which a high-resolution optical pulse shaper and integrated optic phase and intensity modulators are placed, followed by frequency-to-time mapping. The phase and amplitude of each ultrabroadband waveform within the generated sequence can be continuously tuned by adjusting the driving voltages applied to the phase and intensity modulator pair, hence overcoming the slow update speed of conventional spatial light modulator-based pulse shapers. Moreover, this data modulation is completely independent from and does not interfere with RF waveform design. Programmable ultrabroadband RF sequences, spanning more than 4.7 octaves from 2 to 52 GHz, are modulated with real-time data in up to 16 level, M-ary phase-shift keying and quadrature amplitude modulation formats.

A path within the parameter space of detuning and pump power is demonstrated in order to obtain a single cavity soliton (CS) with certainty in SiN microring resonators in the anomalous dispersion regime. Once the single CS state is reached, it is possible to continue a path to compress it, broadening the corresponding single free spectral range (FSR) Kerr frequency comb. The first step to achieve this goal is to identify the stable regions in the parameter space via numerical simulations of the Lugiato-Lefever equation (LLE). Later, using this identification, we define a path from the stable modulation instability (SMI) region to the stable cavity solitons (SCS) region avoiding the chaotic and unstable regions.

Photonic methods of radio-frequency waveform generation and processing can provide performance advantages and flexibility over electronic methods due to the ultrawide bandwidth offered by the optical carriers. However, bulk optics implementations suffer from the lack of integration and slow reconfiguration speed. Here we propose an architecture of integrated photonic radio-frequency generation and processing and implement it on a silicon chip fabricated in a semiconductor manufacturing foundry. Our device can generate programmable radio-frequency bursts or continuous waveforms with only the light source, electrical drives/controls and detectors being off-chip. It modulates an individual pulse in a radio-frequency burst within 4 ns, achieving a reconfiguration speed three orders of magnitude faster than thermal tuning. The on-chip optical delay elements offer an integrated approach to accurately manipulating individual radio-frequency waveform features without constraints set by the speed and timing jitter of electronics, and should find applications ranging from high-speed wireless to defence electronics.

We demonstrate an on-chip four-wave mixing (FWM) scheme in a silicon nanowaveguide to scale the bandwidth of a frequency comb generated by phase modulation of continuous-wave (CW) lasers. The FWM process doubles the bandwidth of the initial comb generated by the modulation of a CW laser. For example, a wavelength-tunable frequency comb with >100 comb lines spaced by 10 GHz within a bandwidth of 5 dB is generated.

The reduced optical bandwidth associated with resonance enhancement poses a significant challenge for resonators to process wide-bandwidth optical data. We report one-way transmission of 10 giga-bit-per-second optical data through a silicon optical diode based on both the resonance-enhanced optical nonlinear effects and resonance reshaping. The diode is operated with a forward-only or backward-only input. In the backward direction, the diode corrupts the data through the strong dispersion and attenuation associated with the resonance of a microring. In the forward direction, the data pass through the diode with negligible distortions because the resonance is red-shifted from the carrier wavelength. In this experimental context the finite bandwidth associated with the optical resonance may be considered beneficial, since the phase response makes an additional contribution to transmission nonreciprocity beyond what is seen with unmodulated light.

We demonstrate the generation of two-photon correlation trains based on spectral filtering of broadband biphotons. Programmable amplitude filtering is employed to create biphoton frequency combs, which when coupled with optical dispersion allows us to experimentally verify the temporal Talbot effect for entangled photons. Additionally, an alternative spectral phase-filtering approach is shown to significantly improve the overall efficiency of the generation process when a comb-like spectrum is not required. Our technique is ideal for the creation of tunable and high-repetition-rate biphoton states.

Optical phase imaging enables visualization of transparent samples, numerical refocusing, and other computational processing. Typically phase is measured quantitatively using interferometric techniques such as digital holography. Researchers have demonstrated image enhancement by synthetic aperture imaging based on digital holography. In this work we introduce a novel imaging technique that implements synthetic aperture imaging using phase retrieval, a non-interferometric technique. Unlike digital holography, phase retrieval obviates the need for a reference arm and provides a more compact, less expensive, and more stable experimental setup. We call this technique synthetic aperture phase retrieval.

We extend orthogonal optical coding, previously applied to multiuser classical communication networks, to entangled photons. Using a pulse shaper and sum-frequency generation for ultrafast coincidence detection, we demonstrate encoding and decoding of biphoton wave packets. Applying one code to the signal photon spreads the wave packet in time and creates a null at zero delay; filtering the idler with the matched code recovers a narrow correlation peak, whereas applying any other code leaves the wave packet spread. Our results could prove useful in the development of code-based quantum communication networks.

Microwave photonic filters with arbitrary phase response can be achieved by merging high-repetition-rate electro-optic frequency comb technology with line-by-line pulse shaping. When arranged in an interferometric configuration, the filter features a number of programmable complex-coefficient taps equal to the number of available comb lines. In this work, we use an ultrabroadband comb generator resulting in a microwave photonic phase filter with >100 complex-coefficient taps. We demonstrate the potential of this filter by performing programmable chirp control of ultrawideband waveforms that extend over long (>10 ns) temporal apertures. This work opens new possibilities for compensating realistic linear distortion impairments on ultrabroadband wireless signals spanning over dozens of nanosecond temporal apertures.

Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 5' untranslated region (5' UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPS-affected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis., (Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

We employed photonic radio frequency (RF) arbitrary waveform generation to demonstrate space-time compression of ultrabroadband wireless signals through highly scattering multipath channels. To the best of our knowledge, this is the first experimental report that explores an RF-photonic transmitter to both characterize channel dispersions in real wireless environments and generate predistorted waveforms to achieve focusing through the multipath channels. Our experiments span a three octave frequency range of 2-18 GHz, nearly an order of magnitude beyond the ~2 GHz instantaneous bandwidth reported in previous spatiotemporal focusing experiments relying on electronic waveform generators.

We introduce a fully programmable two-dimensional (2D) pulse shaper, able to simultaneously control the amplitude and phase of very fine spectral components over a broad bandwidth. This is achieved by aligning two types of spectral dispersers in a cross dispersion setup: a virtually imaged phased array for accessing fine resolution and a transmission grating for achieving broad bandwidth. We take advantage of the resultant 2D dispersion profile as well as introduce programmability by adding a 2D liquid crystal on silicon spatial light modulator at the masking plane. Our shaper has a resolution of ~3 GHz operating over the entire 'C' band of >5.8 THz. Experimental evidence is provided that highlights the full programmability, fine spectral control, and broad bandwidth operation (limited currently by the bandwidth of the input light). We also show line-by-line manipulation of record 836 comb lines over the C-band.

The fundamental quasi-TE and quasi-TM modes of a sub-wavelength strip silicon waveguide are not purely TE or TM as the plane waves in free space. We investigate theoretically and experimentally the far-field polarization compositions of the two waveguide modes after they emanate from the waveguide facet. The measured polarization extinction ratios (PERs) of 31 dB for the quasi-TM mode and 26 dB for quasi-TE mode using free-space polarizers are consistent with our numerical analysis. Moreover, our far-field simulations show that the free-space measurement of PERs is influenced, and in many cases limited, by the sizes of various apertures in the experimental setup. This suggests a potential trade-off between achievable PERs and overall power detection/collection efficiency.

We demonstrate spectral shaping of entangled photons in the telecom band with a programmable, fiber-based optical filter. The fine-resolution spectral control permits implementation of length-40 Hadamard codes, through which we are able to verify frequency anticorrelation with a 20-fold increase in total counts over that permitted by the equivalent pair of monochromators at the same input flux. By programming the complex spectral transmission function corresponding to a Mach-Zehnder interferometer, we also construct variations on Franson interferometers that are free from mechanical instabilities, demonstrating spectral phase independence in the slow-detector limit, in which all temporal features are unobservable. Our configuration furnishes a single, compact arrangement for manipulating telecom biphotons and characterizing their quality.

We demonstrate dispersion cancellation of entangled photons for arbitrary spectral orders, generalizing Franson cancellation typically considered in second order alone. Employing ultrafast coincidence detection based on sum-frequency generation in a periodically poled lithium niobate waveguide with a record-high pair conversion efficiency of 10(-5), we verify cancellation of dispersion up to fifth order. Cancellation of odd-order phase is experimentally shown to require identical signal and idler dispersion coefficients, in contrast to even-order phase, which cancels with opposite signs. These results are especially important for future work on ultrabroadband biphotons.

Background: piggyBac domain (PGBD) transposons are found in organisms ranging from fungi to humans. Three domesticated piggyBac elements have been described. In the ciliates Paramecium tetraurelia and Tetrahymena thermophila, homologs known as piggyMacs excise internal eliminated sequences from germline micronuclear DNA during regeneration of the new somatic macronucleus. In primates, a PGBD3 element inserted into the Cockayne syndrome group B (CSB) gene over 43 Mya serves as an alternative 3' terminal exon, enabling the CSB gene to generate both full length CSB and a conserved CSB-PGBD3 fusion protein that joins an N-terminal CSB domain to the C-terminal transposase domain., Results: We describe a fourth domesticated piggyBac element called PGBD5. We show that i) PGBD5 was first domesticated in the common ancestor of the cephalochordate Branchiostoma floridae (aka lancelet or amphioxus) and vertebrates, and is conserved in all vertebrates including lamprey but cannot be found in more basal urochordates, hemichordates, or echinoderms; ii) the lancelet, lamprey, and human PGBD5 genes are syntenic and orthologous; iii) no potentially mobile ancestral PGBD5 elements can be identified in other more deeply rooted organisms; iv) although derived from an IS4-related transposase of the RNase H clan, PGBD5 protein is unlikely to retain enzymatic activity because the catalytic DDD(D) motif is not conserved; v) PGBD5 is preferentially expressed in certain granule cell lineages of the brain and in the central nervous system based on available mouse and human in situ hybridization data, and the tissue-specificity of documented mammalian EST and mRNA clones; vi) the human PGBD5 promoter and gene region is rich in bound regulatory factors including the neuron-restrictive silencer factors NRSF/REST and CoREST, as well as SIN3, KAP1, STAT3, and CTCF; and vii) despite preferential localization within the nucleus, PGBD5 protein is unlikely to bind DNA or chromatin as neither DNase I digestion nor high salt extraction release PGBD5 from fractionated mouse brain nuclei., Conclusions: We speculate that the neural-specific PGBD5 transposase was domesticated >500 My after cephalochordates and vertebrates split from urochordates, and that PGBD5 may have played a role in the evolution of a primitive deuterostome neural network into a centralized nervous system.

Photonic radio-frequency (RF) arbitrary waveform generation (AWG) based on spectral shaping and frequency-to-time mapping has received substantial attention. This technique, however, is critically constrained by the far-field condition which imposes strict limits on the complexity of the generated waveforms. The time bandwidth product (TBWP) decreases as the inverse of the RF bandwidth which limits one from exploiting the full TBWP available from modern pulse shapers. Here we introduce a new RF-AWG technique which we call near-field frequency-to-time mapping. This approach overcomes the previous restrictions by predistorting the amplitude and phase of the spectrally shaped optical signal to achieve high fidelity waveforms with radically increased TBWP in the near field region.

We use a drop-port geometry to characterize frequency combs generated from silicon nitride on-chip microresonators in the normal group velocity regime. In sharp contrast with the traditional transmission geometry, we observe smooth output spectra with comparable powers in the pump and adjacent comb lines. The power transfer into the comb may be explained to a large extent by the coupling parameters characterizing the linear operation of the resonances studied. Furthermore, comparison of thru- and drop-port spectra shows that much of the ASE noise is filtered out by transmission to the drop-port. Autocorrelation measurements are performed on the drop-port output, without the need to filter out or suppress the strong pump line as is necessary in thru-port experiments. Passively mode-locked pulses with low background are observed in a normal dispersion microcavity.

We present a scheme to generate a 10 GHz optical frequency comb that is bandwidth reconfigurable on a time scale of tens of nanoseconds via electronic control of the drive signal to a phase modulator. When such a comb is used as the source for a radio-frequency (RF) photonic filter employing dispersive propagation, the RF filter bandwidth varies in inverse proportion to the optical bandwidth. As a result we are able to demonstrate, for the first time to our knowledge, bandwidth-reconfigurable RF filtering with transition times under 20 ns. The reconfiguration speed is determined by the response time of a programmable RF variable attenuator.

Through advances in metamaterials--artificially engineered media with exotic properties, including negative refractive index--the once fanciful invisibility cloak has now assumed a prominent place in scientific research. By extending these concepts to the temporal domain, investigators have recently described a cloak which hides events in time by creating a temporal gap in a probe beam that is subsequently closed up; any interaction which takes place during this hole in time is not detected. However, these results are limited to isolated events that fill a tiny portion of the temporal period, giving a fractional cloaking window of only about 10(-4) per cent at a repetition rate of 41 kilohertz (ref. 15)--which is much too low for applications such as optical communications. Here we demonstrate another technique for temporal cloaking, which operates at telecommunication data rates and, by exploiting temporal self-imaging through the Talbot effect, hides optical data from a receiver. We succeed in cloaking 46 per cent of the entire time axis and conceal pseudorandom digital data at a rate of 12.7 gigabits per second. This potential to cloak real-world messages introduces temporal cloaking into the sphere of practical application, with immediate ramifications in secure communications.

The stimulated Raman scattering signal is often accompanied by unwanted background arising from other pump-probe modalities. We demonstrate an approach to overcome this challenge based on spectral domain modulation, enabled by a compact, cost-effective angle-to-wavelength pulse shaper. The pulse shaper switches between two spectrally narrow windows, which are cut out of a broadband femtosecond pulse and selected for on- and off- Raman resonance excitation, at 2.1 MHz frequency for detection of stimulated Raman scattering signal. Such spectral modulation reduced the unwanted pump-probe signals by up to 20 times and enabled stimulated Raman scattering imaging of molecules in a pigmented environment.

The PGBD3 piggyBac transposon inserted into CSB intron 5 early in the primate lineage. As a result of alternative splicing, the human CSB gene now encodes three proteins: CSB, a CSB-PGBD3 fusion protein that joins the N-terminal CSB domain to the C-terminal PGBD3 transposase domain, and PGBD3 transposase. The fusion protein is as highly conserved as CSB, suggesting that it is advantageous in health; however, expression of the fusion protein in CSB-null cells induces a constitutive interferon (IFN) response. The fusion protein binds in vivo to PGBD3-related MER85 elements, but is also tethered to c-Jun, TEAD1, and CTCF motifs by interactions with the cognate transcription factors. The fusion protein regulates nearby genes from the c-Jun (and to a lesser extent TEAD1 and CTCF) motifs, but not from MER85 elements. We speculate that the fusion protein interferes with CSB-dependent chromatin remodeling, generating double-stranded RNA (dsRNA) that induces an IFN response through endosomal TLR or cytoplasmic RIG-I and/or MDA5 RNA sensors. We suggest that the fusion protein was fixed in primates because an elevated IFN response may help to fight viral infection. We also speculate that an inappropriate IFN response may contribute to the clinical presentation of CS., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

A passive all-silicon optical diode is demonstrated to realize a record high nonreciprocal transmission ratio (NTR) of 40 dB. Individual microrings that make up the device are experimentally studied to explain the nonlinear power dynamics. There is a compromise between the NTR and insertion loss, and possible solutions for further improvements are discussed. This work provides a way to realize extremely high optical nonreciprocity on chip for optical information processing applications.

The generation of high-repetition-rate optical frequency combs with an ultra-broad, coherent and smooth spectrum is important for many applications in optical communications, radio-frequency photonics and optical arbitrary waveform generation. Usually, nonlinear broadening techniques of comb-based sources do not provide the required flatness over the whole available bandwidth. Here we present a 10-GHz ultra-broadband flat-topped optical frequency comb (> 3.64-THz or 28 nm bandwidth with ~365 spectral lines within 3.5-dB power variation) covering the entire C-band. The key enabling point is the development of a pre-shaping-free directly generated Gaussian comb-based 10-GHz pulse train to seed a highly nonlinear fiber with normal dispersion profile. The combination of the temporal characteristics of the seed pulses with the nonlinear device allows the pulses to enter into the optical wave-breaking regime, thus achieving a smooth flat-topped comb spectral envelope. To further illustrate the high spectral coherence of the comb, we demonstrate high-quality pedestal-free short pulse compression to the transform-limited duration.

Spectroscopic imaging has been an increasingly critical approach for unveiling specific molecules in biological environments. Toward this goal, we demonstrate hyperspectral stimulated Raman loss (SRL) imaging by intrapulse spectral scanning through a femtosecond pulse shaper. The hyperspectral stack of SRL images is further analyzed by a multivariate curve resolution (MCR) method to reconstruct quantitative concentration images for each individual component and retrieve the corresponding vibrational Raman spectra. Using these methods, we demonstrate quantitative mapping of dimethyl sulfoxide concentration in aqueous solutions and in fat tissue. Moreover, MCR is performed on SRL images of breast cancer cells to generate maps of principal chemical components along with their respective vibrational spectra. These results show the great capability and potential of hyperspectral SRL microscopy for quantitative imaging of complicated biomolecule mixtures through resolving overlapped Raman bands.

Microresonator optical frequency combs based on cascaded four-wave mixing are potentially attractive as a multi-wavelength source for on-chip optical communications. In this paper we compare time domain coherence, radio-frequency (RF) intensity noise, and individual line optical communications performance for combs generated from two different silicon nitride microresonators. The comb generated by one microresonator forms directly with lines spaced by a single free spectral range (FSR) and exhibits high coherence, low noise, and excellent 10 Gbit/s optical communications results. The comb generated by the second microresonator forms initially with multiple FSR line spacing, with additional lines later filling to reach single FSR spacing. This comb exhibits degraded coherence, increased intensity noise, and severely degraded communications performance. This study is to our knowledge the first to simultaneously investigate and observe a correlation between the route to comb formation, the coherence, noise, and optical communications performance of a Kerr comb.

We demonstrate an all-optical transistor with the modulated output signal simultaneously having an output/input ratio > 3 dB and ON/OFF ratio > 20 dB. The microring based device is ultra-compact and CMOS compatible.

High-repetition-rate optical frequency combs can act as broadband photonic mixers and downconvert a microwave signal to an intermediate frequency (IF) band so that it becomes accessible with high-speed electronics. In this Letter, we show that with line-by-line pulse shaping and dispersive propagation, the photonic mixer can simultaneously perform programmable multitap complex-coefficient-filtering within the IF band. This solution opens new possibilities for microwave signal processing by combining the flexibility of optoelectronic frequency comb technology with high-speed analog-to-digital converters.

Recent investigations of microcavity frequency combs based on cascaded four-wave mixing have revealed a link between the evolution of the optical spectrum and the observed temporal coherence. Here we study a silicon nitride microresonator for which the initial four-wave mixing sidebands are spaced by multiple free spectral ranges (FSRs) from the pump. Additional lines then fill in to yield a comb with single FSR spacing, resulting in partial coherence. By using a pulse shaper to select and manipulate the phase of various subsets of spectral lines, we are able to probe the structure of the coherence within the partially coherent comb. Our data demonstrate strong variation in the degree of mutual coherence between different groups of lines and provide support for a simple model of partially coherent comb formation.

The CSB-PGBD3 fusion protein arose more than 43 million years ago when a 2.5-kb piggyBac 3 (PGBD3) transposon inserted into intron 5 of the Cockayne syndrome Group B (CSB) gene in the common ancestor of all higher primates. As a result, full-length CSB is now coexpressed with an abundant CSB-PGBD3 fusion protein by alternative splicing of CSB exons 1-5 to the PGBD3 transposase. An internal deletion of the piggyBac transposase ORF also gave rise to 889 dispersed, 140-bp MER85 elements that were mobilized in trans by PGBD3 transposase. The CSB-PGBD3 fusion protein binds MER85s in vitro and induces a strong interferon-like innate antiviral immune response when expressed in CSB-null UVSS1KO cells. To explore the connection between DNA binding and gene expression changes induced by CSB-PGBD3, we investigated the genome-wide DNA binding profile of the fusion protein. CSB-PGBD3 binds to 363 MER85 elements in vivo, but these sites do not correlate with gene expression changes induced by the fusion protein. Instead, CSB-PGBD3 is enriched at AP-1, TEAD1, and CTCF motifs, presumably through protein-protein interactions with the cognate transcription factors; moreover, recruitment of CSB-PGBD3 to AP-1 and TEAD1 motifs correlates with nearby genes regulated by CSB-PGBD3 expression in UVSS1KO cells and downregulated by CSB rescue of mutant CS1AN cells. Consistent with these data, the N-terminal CSB domain of the CSB-PGBD3 fusion protein interacts with the AP-1 transcription factor c-Jun and with RNA polymerase II, and a chimeric CSB-LacI construct containing only the N-terminus of CSB upregulates many of the genes induced by CSB-PGBD3. We conclude that the CSB-PGBD3 fusion protein substantially reshapes the transcriptome in CS patient CS1AN and that continued expression of the CSB-PGBD3 fusion protein in the absence of functional CSB may affect the clinical presentation of CS patients by directly altering the transcriptional program., Competing Interests: The authors have declared that no competing interests exist.

We introduce a new cascaded four-wave mixing technique that scales up the bandwidth of frequency combs generated by phase modulation of a continuous-wave (CW) laser while simultaneously enhancing the spectral flatness. As a result, we demonstrate a 10 GHz frequency comb with over 100 lines in a 10 dB bandwidth in which a record 75 lines are within a flatness of 1 dB. The cascaded four-wave mixing process increases the bandwidth of the initial comb generated by the modulation of a CW laser by a factor of five. The broadband comb has approximately quadratic spectral phase, which is compensated upon propagation in single-mode fiber, resulting in a 10 GHz train of 940 fs pulses.

Cockayne syndrome is a segmental progeria most often caused by mutations in the CSB gene encoding a SWI/SNF-like ATPase required for transcription-coupled DNA repair (TCR). Over 43Mya before marmosets diverged from humans, a piggyBac3 (PGBD3) transposable element integrated into intron 5 of the CSB gene. As a result, primate CSB genes now generate both CSB protein and a conserved CSB-PGBD3 fusion protein in which the first 5 exons of CSB are alternatively spliced to the PGBD3 transposase. Using a host cell reactivation assay, we show that the fusion protein inhibits TCR of oxidative damage but facilitates TCR of UV damage. We also show by microarray analysis that expression of the fusion protein alone in CSB-null UV-sensitive syndrome (UVSS) cells induces an interferon-like response that resembles both the innate antiviral response and the prolonged interferon response normally maintained by unphosphorylated STAT1 (U-STAT1); moreover, as might be expected based on conservation of the fusion protein, this potentially cytotoxic interferon-like response is largely reversed by coexpression of functional CSB protein. Interestingly, expression of CSB and the CSB-PGBD3 fusion protein together, but neither alone, upregulates the insulin growth factor binding protein IGFBP5 and downregulates IGFBP7, suggesting that the fusion protein may also confer a metabolic advantage, perhaps in the presence of DNA damage. Finally, we show that the fusion protein binds in vitro to members of a dispersed family of 900 internally deleted piggyBac elements known as MER85s, providing a potential mechanism by which the fusion protein could exert widespread effects on gene expression. Our data suggest that the CSB-PGBD3 fusion protein is important in both health and disease, and could play a role in Cockayne syndrome., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We present a programmable multitap microwave photonic filter with an arbitrary phase response operating over a broad bandwidth. Complex coefficient taps are achieved by optical line-by-line pulse shaping on a 10 GHz flat optical frequency comb using a novel interferometric scheme. Through high-speed real-time measurements, we demonstrate programmable chirp control of a waveform via phase filtering. This achievement enables us to compress broadband microwave signals to their corresponding bandwidth-limited pulse duration., (© 2012 Optical Society of America)

Line-by-line pulse shaping is demonstrated on a 890 MHz repetition rate mode-locked titanium sapphire laser. The high resolution pulse shaper is based on a virtual imaged phased array (VIPA) with a free spectral range of 25 GHz. For our implementation, the mask repeats every VIPA free spectral range, which corresponds to every 28 comb lines. Individual frequency modes from the laser are also resolved using the same VIPA paired with a diffraction grating to achieve a resolution of 357 MHz. Several output waveforms are compared with simulation to understand differences with the ideal case.

A passive optical diode effect would be useful for on-chip optical information processing but has been difficult to achieve. Using a method based on optical nonlinearity, we demonstrate a forward-backward transmission ratio of up to 28 decibels within telecommunication wavelengths. Our device, which uses two silicon rings 5 micrometers in radius, is passive yet maintains optical nonreciprocity for a broad range of input power levels, and it performs equally well even if the backward input power is higher than the forward input. The silicon optical diode is ultracompact and is compatible with current complementary metal-oxide semiconductor processing.

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development.

An optical diode transmits forward 10Gbps data with less than 0.5dB power penalty, while suppressing and distorting backward data with a 11dB nominal power penalty. The nonreciprocal transmission is also demonstrated with a silicon modulator.

We demonstrate 40 dB nonreciprocal transmission at telecommunication wavelengths using an integrated all silicon optical diode. The nonreciprocal transmission ratio is the highest to date for CMOS compatible silicon integrated photonics.

The frequency-to-time mapping technique (also known as the temporal far-field phenomenon) usually requires a significant amount of dispersion to stretch an ultrashort optical pulse so that the intensity profile becomes a scaled replica of its optical spectrum. In this work, we study the near-to-far-field transition and find that the far-field condition can be relaxed in some cases relevant for radio-frequency (RF) waveform generation. This observation has allowed us to achieve intensity signals with an ultrabroad RF bandwidth content., (© 2011 Optical Society of America)

Cellular nucleic acid binding protein (Cnbp) is a highly conserved single-stranded nucleic acid binding protein required for rostral head development. The use of a morpholino that inhibits Cnbp mRNA translation previously revealed a role of Cnbp in balancing neural crest cell apoptosis and proliferation in the developing zebrafish. Here, we report the use of another morpholino that specifically modifies the splicing of Cnbp pre-mRNA resulting in a reduction of full-length mRNA levels along with the generation of a novel transcript coding for an isoform that may act as dominant negative proteins. The use of this morpholino resulted in more severe phenotypes that enabled us to demonstrate that Cnbp loss-of-function adversely affects the formation and survival of craniofacial cartilaginous structures not only controlling the ratio of cell proliferation and apoptosis but also defining skeletogenic neural crest cell fate., (© 2011 The Authors. Development, Growth & Differentiation © 2011 Japanese Society of Developmental Biologists.)

We present a photonically enabled rf arbitrary waveform generator that can rapidly switch between two output waveforms. This method is based on line-by-line shaping of an optical comb and then converting the optical pulses to rf waveforms with a fast photodetector. It uses a single diode laser as the optical source and selects different patterns preprogrammed into an optical pulse shaper by shifting the laser frequency. We demonstrate minimum update delay times of 0.45 ns.

With two nonoverlapping beams incident at different angles on a heavily scattering medium, the spatial correlation of speckle patterns over source position has a beat that is related to the incident angle difference. A model presented explains the measurement. The spatial correlation is shown to decorrelate faster than the beam intensity correlation function and to be sensitive to the incident field profile. Increased scatter results in more rapid decorrelation. This work suggests new opportunities for imaging through scattering media.

Cellular nucleic acid binding protein (CNBP) has been implicated in vertebrate craniofacial development and in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human diseases. In these seemingly unrelated biological processes, CNBP appears to be involved in controlling cell death and proliferation rates. Low levels of CNBP may reduce rate of global protein synthesis, thereby reducing proliferation and increasing apoptosis. Conversely, CNBP might affect transcription of genes required for cell proliferation. Experimental evidences gathered so far make it difficult to ascertain or rule out any of these possibilities. Moreover, both possibilities may not be mutually exclusive. CNBP is a small and strikingly conserved single-stranded nucleic acid binding protein that is able to bind DNA as well as RNA. CNBP has a broad spectrum of targets, ranging from regulatory sites in gene promoters to translational regulatory elements in mRNA untranslated regions. Biochemical experiments have recently shed light on the possible mechanism of action for CNBP, which may act as a nucleic acid chaperone catalyzing the rearrangement of G-rich nucleic acid secondary structures likely relevant for transcriptional and/or translational gene regulation. This review focuses on the involvement of CNBP in vertebrate craniofacial development and human DM2 and sIBM diseases, as well as on the biochemical and structural features of CNBP and its cellular and molecular mechanism of action.

We demonstrate a scheme based on a cascade of lithium niobate intensity and phase modulators driven by specially tailored RF waveforms to generate an optical frequency comb with very high spectral flatness. In this Letter, we demonstrate a 10 GHz comb with 38 comb lines within a spectral power variation below 1 dB. The number of comb lines that can be generated is limited by the power handling capability of the phase modulator, and this can be scaled without compromising the spectral flatness. Furthermore, the spectral phase of the generated combs in our scheme is almost purely quadratic, which, as we will demonstrate, allows for high-quality pulse compression using only single-mode fiber.