Continuous compensation of the phase mismatch by using temperature gradients for second harmonic generation

The second harmonic of an infrared laser generated by frequency doubling in a nonlinear crystal can be adversely affected by group delay dispersion applied to the fundamental radiation. Yet large amounts of group delay dispersion can be advantageous when using periodically poled crystals with a linearly chirped period. We propose to achieve the same effects with continuous variation of the phase mismatch in the propagation direction, by applying a temperature gradient to a lithium triborate crystal. Advantageously the temperature gradient can be adjusted depending on the desired results. We demonstrate, through both simulation and experiment, an improvement in not only second harmonic conversion efficiency and beam quality, but also that the second harmonic duration and is bandwidth can be controlled with the temperature gradient

Peculiarities of second harmonic generation with chirped femtosecond pulses at high conversion efficiency

Frequency doubling of an infrared laser radiation in non-linear optical crystals is a widely used technique to obtain light in the visible range. The second harmonic generation process is influenced by several well-known parameters. In this article we study the effect of group delay dispersion on the second harmonic generation process for femtosecond pulses. We show, both through simulation and experiments, that for certain parameters even a small amount of chirp can have a detrimental effect on the conversion efficiency as well as the second harmonic beam quality. We also check the effect of higher order dispersion. By properly accounting for those effects the crystal length and focusing conditions can be optimized to reach high conversion efficiency, while maintaining low sensitivity to chirp variations and good beam quality

Investigation of materials for supercontinuum generation for subsequent nonlinear parametrical and Raman amplification at 1 MHz repetition rate

In the present work we performed research of supercontinuum generation in several commonly used and new supercontinuum generation crystals for subsequent nonlinear amplification, using 1-3 mu J energy pulses of 300 fs duration at 1 MHz repetition rate. Obtained supercontinuum spectra spanning over 480-1950 nm wavelength range at pump pulse energies as low as 200nJ in KGW and YVO4 crystals. We present simple experimental setups of stimulated Raman amplification and optical parametric amplification using supercontinuum seeds obtained from several selected crystals. We achieved total energy conversion efficiencies up to 9% both for optical parametric amplification setup and for stimulated Raman amplification setups. The optical parametric amplifier was tunable in the 680-980 nm spectral range and produced ultrashort pulses of 23-44 fs duration. Raman amplifier produced more than 130 mW average power at 1194 nm wavelength and featured broadened spectrum corresponding to Fourier transform limited similar to 100 fs pulse duration. We demonstrated that low power and low energy femtosecond lasers could be efficiently employed for the nonlinear wavelength conversion

Mapping Biological Current Densities With Ultrafast Acoustoelectric Imaging: Application to the Beating Rat Heart

Ultrafast acoustoelectric imaging (UAI) is a novel method for the mapping of biological current densities, which may improve the diagnosis and monitoring of cardiac activation diseases such as arrhythmias. This paper evaluates the feasibility of performing UAI in beating rat hearts. A previously described system based on a 256-channel ultrasound research platform fitted with a 5-MHz linear array was used for simultaneous UAI, ultrafast B-mode, and electrocardiogram (ECG) recordings. In this paper, rat hearts (n = 4) were retroperfused within a Langendorff isolated heart system. A pair of Ag/Cl electrodes were positioned on the epicardium to simultaneously record ECG and UAI signals for imaging frame rates of up to 1000 Hz and a mechanical index of 1.3. To account for the potential effect of motion on the UAI maps, acquisitions for n = 3 hearts were performed with and without suppression of the mechanical contraction using 2,3-butanedione monoxime. Current densities were detected for all four rats in the region of the atrio-ventricular node, with an average contrast-to-noise ratios of 12. The UAI signals' frequency matched the sinus rhythm, even without mechanical contraction, suggesting that the signals measured correspond to physiological electrical activation. UAI signals appeared at the apex and within the ventricular walls with a delay estimated at 29 ms. Finally, the signals from different electrode positions along the myocardium wall showed the possibility of mapping the electrical activation throughout the heart. These results show the potential of UAI for cardiac activation mapping in vivo and in real time

The density of Tbet+ tumor-infiltrating T lymphocytes reflects an effective and druggable preexisting adaptive antitumor immune response in colorectal cancer, irrespective of the microsatellite status

International audiencePurpose: The recent success of anti-PD1 antibody in metastatic colorectal cancer (CRC) patients with microsatellite instability (MSI), known to be associated with an upregulated Th1/Tc1 gene signature, provides new promising therapeutic strategies. However, the partial objective response highlights a crucial need for relevant, easily evaluable, predictive biomarkers. Here we explore whether in situ assessment of Tbet+ tumor infiltrating lymphocytes (TILs) reflects a pre-existing functional antitumor Th1/Tc1/IFNγ response, in relation with clinicopathological features, microsatellite status and expression of immunoregulatory molecules (PD1, PDL1, IDO-1). Methodology: In two independent cohorts of CRC (retrospective n = 80; prospective n = 27) we assessed TILs density (CD3, Tbet, PD1) and expression profile of PDL1 and IDO-1 by immunohistochemistry/image analysis. Furthermore, the prospective cohort allowed to perform ex vivo CRC explant cultures and measure by Elisa the IFNγ response, at baseline and upon anti-PD1 treatment. Results: The density of Tbet+ TILs was significantly higher in MSI CRC, especially in the medullary subtype but also in a subgroup of MSS (microsatellite stable), and positively correlated with PD1 and PDL1 expression, but not with IDO-1. Finally, a high number of Tbet+ TILs was associated with a favorable overall survival. These Tbet+ TILs were functional as their density positively correlated with basal IFNγ levels. In addition, the combined score of Tbet+ PD1+ TILs coupled with IDO-1 expression predicted the magnitude of the IFNγ response upon anti-PD1. Conclusion: Altogether, immunohistochemical quantification of Tbet+ TILs is a reliable and accurate tool to recapitulate a preexisting Th1/Tc1/IFNγ antitumor response that can be reinvigorated by anti-PD1 treatment