Quantum-Path-Resolved Attosecond High-Harmonic Spectroscopy.

Strong-field ionization of molecules releases electrons which can be accelerated and driven back to recombine with their parent ion, emitting high-order harmonics. This ionization also initiates attosecond electronic and vibrational dynamics in the ion, evolving during the electron travel in the continuum. Revealing this subcycle dynamics from the emitted radiation usually requires advanced theoretical modeling. We show that this can be avoided by resolving the emission from two families of electronic quantum paths in the generation process. The corresponding electrons have the same kinetic energy, and thus the same structural sensitivity, but differ by the travel time between ionization and recombination-the pump-probe delay in this attosecond self-probing scheme. We measure the harmonic amplitude and phase in aligned CO_{2} and N_{2} molecules and observe a strong influence of laser-induced dynamics on two characteristic spectroscopic features: a shape resonance and multichannel interference. This quantum-path-resolved spectroscopy thus opens wide prospects for the investigation of ultrafast ionic dynamics, such as charge migration.

Fast and precise chiroptical spectroscopy by photoelectron elliptical dichroism.

The photoionization of chiral molecules by elliptically polarized femtosecond laser pulses produces photoelectron angular distributions which show a strong and enantio-sensitive forward/backward asymmetry along the light propagation direction. We report on high precision measurements of this photoelectron elliptical dichroism (PEELD). Using an optical cavity to recycle the laser pulses and increase the signal-to-noise ratio, we determine enantiomeric excesses with a 0.04% precision with a low-power femtosecond laser (4 W) in a compact scheme. We perform momentum-resolved PEELD measurements in 16 molecules, from volatile terpenes to non-volatile amino acids and large iodoarenes. The results demonstrate the high structural sensitivity of PEELD, confirming the spectroscopic interest of this technique. Last, we show how a convolutional neural network can be used to retrieve the chemical and enantiomeric composition of a sample from the momentum-resolved PEELD maps.

Role of periosteum during healing of alveolar critical size bone defects in the mandible: a pilot study.

OBJECTIVES: Minipigs present advantages for studying oral bone regeneration; however, standardized critical size defects (CSD) for alveolar bone have not been validated yet. The objectives of this study are to develop a CSD in the mandibular alveolar bone in Aachen minipigs and to further investigate the specific role of periosteum. MATERIALS AND METHODS: Three female Aachen minipigs aged 17, 24, and 84 months were used. For each minipig, a split-mouth design was performed: an osteotomy (2 cm height × 2.5 cm length) was performed; the periosteum was preserved on the left side and removed on the right side. Macroscopic, cone beam computed tomography (CBCT), microcomputed tomography (µCT), and histological analyses were performed to evaluate the bone defects and bone healing. RESULTS: In both groups, spontaneous healing was insufficient to restore initial bone volume. The macroscopic pictures and the CBCT results showed a larger bone defect without periosteum. µCT results revealed that BMD, BV/TV, and Tb.Th were significantly lower without periosteum. The histological analyses showed (i) an increased osteoid apposition in the crestal area when periosteum was removed and (ii) an ossification process in the mandibular canal area in response to the surgical that seemed to increase when periosteum was removed. CONCLUSIONS: A robust model of CSD model was developed in the alveolar bone of minipigs that mimics human mandibular bone defects. This model allows to further investigate the bone healing process and potential factors impacting healing such as periosteum. CLINICAL RELEVANCE: This model may be relevant for testing different bone reconstruction strategies for preclinical investigations.

Photoelectron elliptical dichroism spectroscopy of resonance-enhanced multiphoton ionization via the 3s, 3p and 3d Rydberg series in fenchone.

The resonance-enhanced multiphoton ionization of chiral molecules by elliptically polarized laser pulses produces photoelectron angular distributions that are forward/backward asymmetric with respect to the light propagation axis. We investigate this photoelectron elliptical dichroism in the (2 + 1)-photon ionization of fenchone molecules, using wavelength tunable femtosecond UV pulses. We show that the photoelectron elliptical asymmetry is extremely sensitive to the intermediate resonant states involved in the ionization process, and enables electronic couplings to be revealed that do not show up so clearly when using circularly polarized light.

High-power sub-15 fs nonlinear pulse compression at 515 nm of an ultrafast Yb-doped fiber amplifier.

We present an efficient and robust scheme to produce energetic sub-15 fs pulses centered at 515 nm with a peak power exceeding 3 GW. Combining efficient second-harmonic generation of a 135 fs, 50 W Yb-doped fiber amplifier with a low-loss capillary-based visible pulse compression stage, we reach an overall efficiency higher than >20%. The system is also designed to take advantage of the repetition rate flexibility of the fiber amplifier, leading sub-15 fs pulse generation from 166 to 500 kHz with an average power exceeding the 10 watt level. The combined reduction of the laser wavelength and pulse duration is expected to highly improve the yield of high-order harmonic generation to provide high photon flux of ultrashort extreme ultraviolet radiation.

Ultrafast relaxation investigated by photoelectron circular dichroism: an isomeric comparison of camphor and fenchone.

We study the isomeric effects using time resolved photoelectron circular dichroism (TR-PECD). Using a (1 + 1') pump-probe ionisation scheme with photoelectrons collected by the velocity map imaging technique, we compare the relaxation dynamics from the 3s-Rydberg state in 1R,4R-(+)-camphor with the one in its chiral isomer, 1R,4S-(-)-fenchone [Comby et al., 2016, JPCL, 7, 4514]. Our measurements revealed a similar lifetime for both isomers. However, the circular dichroism in the photoelectron angular distribution decays exponentially in ∼730 fs from a +9% forward amplitude during the first hundreds of femtoseconds to reach an asymptotic -2% backward amplitude. This time-scale is drastically shorter than in fenchone. Our analysis allows us to evaluate the impact of the anisotropy of excitation; the relaxation dynamics, following photoexcitation by the linearly polarized pump, is then compared to that induced by a circularly polarized pump pulse (CPL). With such a CPL pump, we then retrieve time constants of our chiral observables similar to the ones recorded in fenchone. Quantum and classical simulations are developed and used to decipher the dependence of the PECD on the anisotropy of excitation and the spatial distribution of the 3s-Rydberg electron wavefunction. Our experimental investigations, supported by our simulations, suggest that varying the pump ellipticity enables us to reveal the breakdown of the Franck-Condon approximation.

Aromatic Formation Promoted by Ion-Driven Radical Pathways in EUV Photochemical Experiments Simulating Titan's Atmospheric Chemistry.

In the atmosphere of Titan, Saturn's main satellite, molecular growth is initiated by 85.6 nm extreme ultraviolet (EUV) photons triggering a chemistry with charged and free-radical species. However, the respective contribution of these species to the complexification of matter is far from being known. This work presents a chemical analysis in order to contribute to a better understanding of aromatic formation pathways. A gas mixture of N2/CH4 (90/10%) within the closed SURFACAT reactor was irradiated at a relatively low pressure (0.1 mbar) and room temperature for 6 h by EUV photons (∼85.6 nm). The neutral molecules formed at the end of the irradiation were condensed in a cryogenic trap and analyzed by electron ionization mass spectrometry. An analysis of the dominant chemical pathways highlights the identification of benzene and toluene and underlies the importance of small ion and radical reactions. On the basis of the experimental results, a speculative mechanism based on sequential H-elimination/CH3-addition reactions is proposed for the growth of aromatics in Titan's atmosphere. Elementary reactions to be studied are given to instill future updates of photochemical models of Titan's atmosphere.

Single-shot phase-matching free ultrashort pulse characterization based on transient absorption in solids.

The frequency-resolved optical switching (FROSt) method developed for ultrashort pulse characterization is implemented for single-shot measurements. In this basic demonstration, the delay axis of the spectrogram is spatially encoded by the pump beam having a small incident angle with the photoexcited material. We present the calibration procedure for spectrograms acquired in single-shot and the temporal characterization of 44 fs pulses with central wavelength at 800 nm both in scanning and single-shot FROSt configurations. The retrieved pulses are compared by means of the root-mean-square field error. Finally, the pulses are propagated through a known dispersive material to measure the added group-delay dispersion.

39 W narrow spectral linewidth monolithic ytterbium-doped fiber MOPA system operating at 976 nm.

We report on a monolithic narrow spectral linewidth master oscillator power amplifier (MOPA) delivering up to 39 W around 976 nm with very high contrast. The amplifier is based on an ytterbium-doped large mode area (LMA) octagonal double clad (DC) active fiber with parameters optimized for long living three-level operation.

Using photoelectron elliptical dichroism (PEELD) to determine real-time variation of enantiomeric excess.

In this work, the photoionization of chiral molecules by an elliptically polarized, high repetition rate, femtosecond laser is probed. The resulting 3D photoelectron angular distribution shows a strong forward-backward asymmetry, which is highly dependent not only on the molecular structure but also on the ellipticity of the laser pulse. By continuously varying the laser ellipticity, we can observe molecular and enantiomer changes in real time at a previously unseen speed and precision. The technique allows enantiomeric excess of a pure compound to be measured with a 5% precision within 3 s, and a 10-min acquisition yields a precision of 0.4%. The isomers camphor and fenchone can be easily distinguished, unlike with conventional mass spectrometry. Preliminary results for the pharmaceutically interesting ibuprofen are also given, showing the capability of photoionization as a means of distinguishing larger molecular systems.

Ultrafast electronic relaxations from the S3 state of pyrene.

The ultrafast relaxation occurring in pyrene upon excitation at 4.68 eV was studied in a supersonic gas-jet fs pump-probe experiment. Mass spectrometry and velocity map imaging of photoelectrons produced by probing via multiphoton ionisation at 800 nm reveal that the initially prepared wave packet exhibits a fast relaxation (<80 fs), followed by a slower one of 200 fs. By comparing the propensity rules of photoionisation observed at one color with ab initio calculations, we tentatively assign these two timescales to a first internal conversion to the dark bB3g state followed by a second one to the long lived aB2u first excited state. Vertical excitation energies determined using ab initio Multi-State Complete Active Space 2nd order Perturbation Theory (MS-CASPT2), as well as oscillator strengths between several electronic states, are reported.

Distorted Patterns of Dentinogenesis and Eruption in Msx2 Null Mutants: Involvement of Sost/Sclerostin.

The muscle segment homeogenes Msx1 and Msx2 play a major role in tooth and bone formation. Periodontal osteoclast impairment also occurs in Msx2 null mutant mice, which is restored by overexpression of the receptor activator of NF-κB targeted in osteoclast lineage. Here, we investigated the role of Msx2 in dentinogenesis. Experiments were performed on Msx2(-/-) mice and the MDPC-23 odontoblastic cell line. After Msx2 gene silencing, real-time quantitative RT-PCR data showed significant overexpression of Runx2, Bglap, Dspp, and Alpl. Of three inhibitors of Wnt/ß-catenin signaling (Dkk1, SostDc1, and Sost/Sclerostin), only Sost was expressed in postnatal teeth and overexpressed in Msx2(-/-) tooth samples. Initial crown dentin formation-primary dentinogenesis-occurred fairly normally in Msx2(-/-) teeth, albeit with distorted cusp patterns. Later stages of tooth development were characterized by a deviation from secondary toward tertiary dentinogenesis with osteodentin formation and impaired dentin deposition leading to limited root elongation. In Msx2(-/-)/receptor activator of NF-κB-transgenic double mutants, the dentin phenotype, notably in the roots, was rescued and sclerostin levels were normalized. These data suggest that Msx2 may act indirectly on dentinogenesis by controlling osteoclast activity and the signaling network related to eruption, supporting and further extending the concept that Msx2 controls formation of mineralized tissues by inhibition of the Wnt/ß-catenin pathway; Sost in dentin and Dkk1 in bone, as previously demonstrated.

100 kHz Yb-fiber laser pumped 3 µm optical parametric amplifier for probing solid-state systems in the strong field regime.

We report on a laser source operating at 100 kHz repetition rate and delivering 8 µJ few-cycle mid-IR pulses at 3 µm. The system is based on optical parametric amplification pumped by a high repetition rate Yb-doped femtosecond fiber-chirped amplifier. This high-intensity ultrafast system is a promising tool for strong-field experiments (up to 50 GV/m and 186 T) in low ionization potential atomic and molecular systems, or solid-state physics with coincidence measurements. As a proof of principle, up to the sixth harmonic has been generated in a 1 mm zinc selenide sample.

Study of middle infrared difference frequency generation using a femtosecond laser source in LGT.

We demonstrate phase-matched difference frequency generation in the emerging nonlinear crystal La3Ga5.5Ta0.5O14. Tunable wavelengths between 1.4 and 4.7 µm are generated by using femtosecond sources. We also report on the measurements of the optical damage threshold in the femtosecond regime and on the nonlinear refractive index n2.

Femtosecond versus picosecond laser pulses for film-free laser bioprinting.

We investigate the properties of microjets in the context of film-free laser induced forward transfer in the femtosecond and picosecond regimes. The influence of the pulse duration (ranging from 0.4 to 12 ps) and the energy (ranging from 6 to 12 µJ) is systematically studied on the height, diameter, speed, volume, and shape of the jets. The 400 fs pulses generate thin and stable jets compatible with bioprinting, while 14 ps pulses generate more unstable jets. A pulse duration around 8 ps seems, therefore, to be an interesting trade-off to cover many bio-applications of microjets generated by lasers.

Using high harmonic radiation to reveal the ultrafast dynamics of radiosensitiser molecules.

5-Fluorouracil (5FU) is a radiosensitiser molecule routinely used in combined chemo- and radio-therapies to enhance and localize cancer treatments. We have employed ultra-short XUV pulses produced by high harmonic generation (HHG) as a pump pulse to study the dynamics underlying the photo-stability and the radiation damage of this molecule. This work shows that it is possible to resolve individual dynamics even when using unselected HH. By comparing the results with those obtained in the multiphoton absorption at 400 nm, we were able to identify the frequencies of the HH comb relevant to the recorded dynamics: HH5 and HH3. The latter excites a high-lying Rydberg state interacting with a valence state and its dynamics is revealed by a 30 fs decay signal in the parent ion transient. Our results suggest that the same photoprotection mechanisms as those conferring photostability to the neutral nucleobases and to the DNA appear to be activated: HH5 excites the molecule to a state around 10.5 eV that undergoes an ultrafast relaxation on a timescale of 30 fs due to nonadiabatic interactions. This is followed sequentially by a 2.3 ps internal conversion as revealed by the dynamics observed for another fragment ion. These dynamics are extracted from the fragment ion signals. Proton or hydrogen transfer processes are required for the formation of three fragments and we speculate that the time scale of one of the processes is revealed by a H+ transient signal.

Probing ultrafast dynamics of chiral molecules using time-resolved photoelectron circular dichroism.

Measuring the ultrafast dynamics of chiral molecules in the gas phase has been a long standing and challenging quest of molecular physics. The main limitation to reach that goal has been the lack of highly sensitive chiroptical measurement. By enabling chiral discrimination with up to several 10% of sensitivity, photoelectron circular dichroism (PECD) offers a solution to this issue. However, tracking ultrafast processes requires measuring PECD with ultrashort light pulses. Here we compare the PECD obtained with different light sources, from the extreme ultraviolet to the mid-infrared range, leading to different ionization regimes: single-photon, resonance-enhanced multiphoton, above-threshold and tunnel ionization. We use single and multiphoton ionization to probe the ultrafast relaxation of fenchone molecules photoexcited in their first Rydberg states. We show that time-resolved PECD enables revealing dynamics much faster than the population decay of the Rydberg states, demonstrating the high sensitivity of this technique to vibronic relaxation.

Combined high-harmonic interferometries for vectorial spectroscopy.

We present a new method to characterize transverse vectorial light produced by high-harmonic generation (HHG). The incoherent sum of the two components of the electric field is measured using a bi-dimensional transient grating while one of the components is simultaneously characterized using two-source interferometry. The combination of these two interferometric setups enables the amplitude and phase measurement of the two vectorial components of the extreme ultraviolet radiation. We demonstrate the potential of this technique in the case of HHG in aligned nitrogen, revealing the vectorial properties of harmonics 9-17 of a Ti:sapphire laser.

Enhanced high harmonic generation driven by high-intensity laser in argon gas-filled hollow core waveguide.

We show that a significant enhancement of the photon flux produced by high harmonic generation can be obtained through guided configuration at high laser intensity largely above the saturation intensity. We identify two regimes. At low pressure, we observe an intense second plateau in the high harmonic spectrum in argon. At relatively high pressure, complex interplay between strongly time-dependent ionization processes and propagation effects leads to important spectral broadening without loss of spectral brightness. We show that the relevant parameter for this physical process is the product of laser peak power by gas pressure. We compare source performances with high harmonic generation using a gas jet in loose focusing geometry and conclude that the source developed is a good candidate for injection devices such as seeded soft x-ray lasers or free electron lasers in the soft x-ray range.

Human dental pulp stem cells derived extracellular matrix promotes mineralization via Hippo and Wnt pathways.

Extracellular matrix (ECM) is an intricate structure providing the microenvironment niche that influences stem cell differentiation. This study aimed to investigate the efficacy of decellularized ECM derived from human dental pulp stem cells (dECM_DPSCs) and gingival-derived mesenchymal stem cells (dECM_GSCs) as an inductive scaffold for osteogenic differentiation of GSCs. The proteomic analysis demonstrated that common and signature matrisome proteins from dECM_DPSCs and dECM_GSCs were related to osteogenesis/osteogenic differentiation. RNA sequencing data from GSCs reseeded on dECM_DPSCs revealed that dECM_DPSCs upregulated genes related to the Hippo and Wnt signaling pathways in GSCs. In the inhibitor experiments, results revealed that dECM_DPSCs superiorly promoted GSCs osteogenic differentiation, mainly mediated through Hippo and Wnt signaling. The present study emphasizes the promising translational application of dECM_DPSCs as a bio-scaffold rich in favorable regenerative microenvironment for tissue engineering.