Ultrafast laser pulse characterization is extremely important in applications like high-harmonic spectroscopy, ultrafast imaging or time resolved measurements. The most practical, reliable and well developed method for ultrashort pulse characterization is frequency resolved optical gating (FROG). This method uses different algorithms to retrieve the ultrashort pulse amplitude and phase from a FROG spectrogram. Convolutional neural networks can be an alternative to the classically used algorithms due to their high computational speed and superior performance in processing images. In this article, two convolutional neural networks are developed in order to accurately predict the real and imaginary parts of the complex spectral electric field based on FROG images that do not require a pre-processing step. The data on which the neural network is trained, validated and tested is generated using parameters of the chirped pulse amplification system at the ELI-NP facility, which are chosen to be in an experimentally viable range and are used to calculate the phase of the laser pulse. The low errors between the original and retrieved complex spectral electric field confirm the excellent prediction capabilities of these two fast neural networks.

The propagation of femtosecond pulses in guided structures is a matter of both fundamental and practical interest in nonlinear optics. In particular, hollow-core waveguides (HCWs) filled with a gas medium are fabricated and used as devices for the generation of attosecond pulses from high-order harmonics. In this process, the configuration of the laser field (intensity and phase) inside the waveguide is of crucial importance for enhancing the (well-known, low) efficiency of high-order harmonic generation (HHG). Here, we present numerical calculations which demonstrate the main features of the propagation process in fabricated HCWs. We consider a variety of experimental parameters like gas pressure, waveguide size, laser wavelength, and pulse energy and duration. In particular, the beam profile at the fiber input is found to be a sensitive parameter which influences the whole evolution of the laser field along the propagation. Our model is based on a split-step method modified to account for propagation in ionized media and is validated against experimental and theoretical data from the literature. Our results contribute to the description of the main features of beam propagation in HCWs and provide guiding directions for designing efficient configurations for HHG.

In the development of a pharmaceutical drug product packaging, an important step is to demonstrate acceptable levels of leachable impurities migrating from the packaging material into the drug product during its shelf life and therapeutic use. Such migration processes can be quantified either by analytical methods (which is often challenging and labor intensive) or (in many cases) through theoretical modeling, which is a reliable, quick, and cost-effective method to forecast the level of leachable impurities in the packaged drug when the diffusion and partition coefficients are known. In the previous part, it was shown how these parameters can be determined experimentally, and subsequent theoretical fitting of the results for a series of low- and high-molecular-weight organic compounds (known leachables) in a series of polyolefin materials was performed. One of the interpretations of these results is that a theoretical calculation can be made only for organic compounds and materials whose diffusion/partition/solubility coefficients were determined experimentally and theoretical fitting was achieved. However, in practice, there will be situations in which other leachable compounds may have to be investigated. In such cases, strictly speaking, it would be necessary to perform the whole experimental and fitting procedure for the new compound before a proper theoretical modeling is possible. But this would make the theoretical calculation of a leaching process from a pharmaceutical packaging material a cumbersome and cost intensive procedure. To address this problem, the pools of diffusion and partition coefficients were used to develop an approach that allows the estimation, without any additional experimentation, of so-called "conservative" diffusion and partition coefficients for a much wider range of potential leachables in the polyolefin pharmaceutical packaging materials and aqueous solutions investigated previously.

We present a compact high-harmonic generation approach – termed as strongly overdriven regime – providing continuum radiation ranging from 18 to 140 eV albeit using long driving laser pulses, acting as a flexible and intense extreme-ultraviolet source.

An important step in the development of a pharmaceutical drug product is to demonstrate acceptable levels of leachable impurities during the shelf-life and therapeutic use of the drug product. If the diffusion and partition coefficients are known, the concentration profile of a leachable impurity in the drug product can be predicted theoretically at a given temperature and time. With this objective in mind, kinetic experiments were performed to study the migration of low- to high-molecular-weight organic compounds from mono- and multilayer polyolefin films. Migration curves at different temperatures were generated for each compound when these films were brought in contact with aqueous solutions with varying pH or with another plastic film made from a different polyolefin material. "Best fit" migration curves and the corresponding diffusion and partition coefficients (about 300 pieces) were obtained by using numerical software developed by FABES. The results obtained show that, in general, the correlation between the calculated diffusion and partition coefficients and temperature, between 30°C and 85°C, obeys the Arrhenius and Van't Hoff equations. In this temperature range, the diffusion and partition coefficients can be used to model and predict migration of the investigated compounds from the same pharmaceutical packaging materials. A comparison of these coefficient values with other polyolefin films also provides insights into the chemistry of the mono- and multilayers and the impact it has on the migration behavior of the compounds. In a consecutive paper, an approach to overestimate the diffusion and partition coefficients to account for the variability in experimental data is explained and finally, the use of these overestimated parameters to predict the concentrations for other compounds leaching from the multilayer films into aqueous drug product formulations is discussed.

Ultrafast X-ray spectroscopy allows studying light-matter interaction with an unprecedented temporal resolution, with the further advantage of being element-selective and oxidation- and spin-state specific. Here we will discuss the recent developments we implemented toward attosecond X-ray spectroscopy based on tabletop sources, namely a bright XUV source based on high-order harmonic generation in micro-channels and a new beamline for XUV transient absorption spectroscopy experiments up to a few hundred eV.

We explore via numerical modeling the generation of very short photon wavelengths in hollow core waveguides (HCW) filled with He gas at high pressures. Propagation of femtosecond driving pulses is first solved using a split-step method and tested against other methods. The propagation along the HCW reveals mode beating seen in quasi-periodic oscillations of the field intensity and phase which in turn will determine the single atom response to the field. We explore both cylindrical and conical HCW in which the guide diameter varies along the propagation direction. This second configuration generates very high harmonic orders in a regime of quasi-phase matching. We found three spectral ranges which show amplification, at 3.5, 7.6, and 11-13 nm, which are of great interest given their practical applications in spectroscopy, XUV metrology and photolithography.

We numerically investigate generation of harmonics in the water window region (down to 2.8 nm) by 2 μm femtosecond pulses propagating in hollow core waveguides filled with high pressure He. Numerical calculations are based on a three dimensional macroscopic model, which solves the pulse propagation by a split-step method, uses the strong field approximation to evaluate the single atom response, and integrates it coherently to obtain the harmonic field. Two configurations for the waveguides are considered: the standard one with a constant diameter of 70 μm and a conical one with a decreasing diameter from 70 to 50 μm. We demonstrate that harmonic field enhancement can be obtained in spectral domains of great practical interest, from 2.8 to 20 nm, and identify quasi-phase matching induced by multimode beating as the mechanism responsible for this enhancement.

High-harmonic generation (HHG) normally requires a careful adjustment of the driving laser intensity (typically $10^{14} - 10^{15}$ W/cm$^2$) and gas medium parameters to enable good phase matching conditions. In contrast with conventional wisdom, we present experimental results indicating phase-matched HHG in all rare gases, using a high-density medium and a driver laser intensity of around $10^{16}$ W/cm$^2$. The experimental results are corroborated by theoretical simulations, which indicate that ionization-induced self-phase modulation and plasma defocusing self-regulate the driver laser intensity to a level that is appropriate for good phase matching. A ten-fold broadening of the NIR spectrum is observed, which results in the generation of continuous spectra from $18-140$ eV in spite of using 50-fs-long driving pulses. The presented scheme represents a simple and versatile concept for the generation of XUV and soft X-ray continua, which are ideally suited for transient absorption and reflection spectroscopy.

We report on the reconstruction of ultrashort laser pulses from computer-simulated and experimental second harmonic generation-frequency resolved optical gating (SHG-FROG) spectrograms. In order to retrieve the spectral amplitude and phase we use a convolutional neural network trained on simulated SHG-FROG spectrograms and the corresponding spectral-domain fields employed as labels for the network, which is a complex field encompassing the full information about the amplitude and phase. Our results show excellent retrieval capabilities of the neural network in case of the simulated pulses. Although trained only on computer generated data, the method shows promising results regarding experimentally measured pulses.

Filamentation is a nonlinear optical phenomenon that involves the interplay between Kerr lens self-focusing and plasma defocusing, holding promise for practical applications in open-air environments over long distances. This process significantly alters the characteristics of laser pulses, making the control of laser properties a pivotal issue. In this study, we investigated the effects of laser energy and chirp on the spectral modulation of femtosecond laser pulses caused by filamentation in air. Negatively and positively chirped pulses exhibit distinct characteristics in the spectra measured after the filamentation. Negatively chirped pulses have broader spectral broadening and a stronger dependence on initial laser energy than positively chirped pulses, making them suitable for generating few-cycle pulses and applications requiring white light. In contrast, positively chirped pulses can be advantageous for applications requiring long-distance transmission of high-energy laser pulse. Our findings reveal the fundamental characteristics of femtosecond laser filamentation in air, thereby expanding the scope of possible atmospheric applications.

Recent advances in Ultrafast laser technologies are boosting the development of compact ultrafast sources of coherent eXtreme UltraViolet (XUV, 10–124 eV) and Soft-X-Ray (SXR, from 124 eV up to a few keV). High order Harmonic Generation (HHG) is a well-established approach to achieving this radiation, with a duration on the attosecond timescale, by table-top ultrafast driving lasers [1].

A safety assessment of recycled high-density polyethylene (rHDPE) in cosmetic packaging was performed based on guidelines published by the European Food Safety Authority (EFSA) on the use of recycled plastics for food packaging. EFSA guidelines require demonstration that the concentration of selected representative chemical contaminants in recycled plastic resulting from exposure from food is lower than the threshold of toxicological concern (TTC) for genotoxic substances of 0.0025 mu g/kg bw/day. To investigate the highest concentration (Cmod) of representative chemical contaminants, that would not exceed the genotoxic TTC, when migrating from rHDPE packaging to foodstuffs, used as cosmetic formulation surrogates, we used mathematical modeling software (MIGRATEST (R) EXP). The Cmod values of representative chemical contaminants were then compared with the EFSA-reported residual concentration (Cres) of each contaminant in the rHDPE. For each of the cosmetic product/packaging combinations evaluated, we found that the modeled values were clearly lower for Cmod than Cres, i.e., the recycling process could effectively reduce potential contaminants of rHDPE to levels that would not result in daily consumer exposure from cosmetic use exceeding the genotoxic TTC. For skin sensitization, we modeled a worst-case scenario and assumed 100 % of each representative chemical contaminant migrates into the cosmetic formulation from rHDPE. We then calculated the consumer exposure level for each contaminant based on the dose per unit area and compared it with the dermal sensitization threshold (DST) for reactive materials, which is 64 mu g/cm2. In each case, we demonstrated that the migration of each representative chemical contaminant from rHDPE into each cosmetic formulation was far below the DST, confirming that there is no appreciable risk of sensitization for protein-reactive chemicals. In conclusion, these data support the safe use of rHDPE in the packaging of cosmetic products for leave-on and rinse-off applications.

The development of compact and bright XUV and soft X-ray sources based on high-order harmonic generation is boosting advances towards understanding the behavior of matter with extreme temporal and spatial resolutions. Here, we report efficient XUV generation inside microfluidic devices fabricated by femtosecond laser irradiation followed by chemical etching. Our microfluidic approach allows one to control and manipulate the generation conditions in gas on a micro-meter scale with unprecedented flexibility, thus enabling a high photon-flux and broadband harmonics spectra up to 200 eV.

Low-lying electronic excited states and their relaxation pathways as well as energetics of the crosslinking reaction between uracil as a model system for pyrimidine-type building blocks of DNA and RNA and benzene as a model system for aromatic groups of tyrosine (Tyr) and phenylalanine (Phe) amino acids have been studied in the framework of density functional theory. The equilibrium geometries of the ground and electronic excited states as well as the crossing points between the potential energy surfaces of the uracil-benzene complex were computed. Based on these results, different relaxation pathways of the electronic excited states that lead to either back to the initial geometry configuration or the dimerization between the six-membered rings of the uracil-benzene complex have been identified, and the energetic conditions for their occurrence are discussed. It can be concluded that the DNA-protein crosslinking reaction can be induced by the external electromagnetic field via the dimerization reaction between the six-membered rings of the uracil-benzene pair at the electronic excited-state level of the complex. In the case of the uracil-phenol complex, the configuration of the cyclic adduct (dimerized) conformation is less likely to be formed.

The development of bright eXtreme UltraViolet (XUV) and soft x-ray sources based on high-order harmonic generation is boosting advances toward understanding the behavior of matter on the attosecond timescale. Here, we report a novel approach for efficient XUV generation consisting of the use of microfluidic integrated systems fabricated by femtosecond laser micromachining of glass. Our microfluidic approach allows one to control and manipulate the gas density on a micrometer scale with unprecedented accuracy and micro-structural flexibility. By propagating ultrashort laser pulses inside the microfluidic devices, we demonstrate high photon fluxes and broadband harmonics spectra, up to 200 eV, from tailored gas media.

In this study we proposed the improvement of the quality of the periodontal images recorded in vitro on a defrozen pig mandible using a spectral domain optical coherent tomography (SD-OCT) handheld operating in 1200–1400 nm infrared domain. Anatomical elements of periodontal tissue necessary to establish the diagnosis of periodontal disease by OCT imaging as a non-contact and non-invasive alternative to periodontal probing could be identified. The anatomical elements could be clearer visualized by using a dedicated imaging processing algorithm, which applied a package of proper filters to remove the noise and the blur, but also to enhance the original images contrast.

Femtosecond laser micromachining is a versatile technique that is broadly used for the fabrication of integrated optics and microfluidic devices. In this work, we present the fabrication and demonstration of a microfluidic device used for high-order harmonic generation in a hollow waveguide filled with helium. We found a higher generation yield and a harmonic spectrum reshaping (at gas baking pressures over 400 mbar) in the hollow waveguide with a smoother surface. We believe that, thanks to the high versatility and three-dimensional capability of this microstructuring technique, in the next future it will be possible to integrate more functionalities in the same glass chip thus paving the way to strong laser field physics in a lab-on-chip.

High-intensity laser pulses covering the ultraviolet to terahertz spectral regions are nowadays routinely generated in a large number of laboratories. In contrast, intense extreme-ultraviolet (XUV) pulses have only been demonstrated using a small number of sources including free-electron laser facilities [1-3] and long high-harmonic generation (HHG) beamlines [4-9]. Here we demonstrate a concept for a compact intense XUV source based on HHG that is focused to an intensity of $2 \times 10^{14}$ W/cm$^2$, with a potential increase up to $10^{17}$ W/cm$^2$ in the future. Our approach uses tight focusing of the near-infrared (NIR) driving laser and minimizes the XUV virtual source size by generating harmonics several Rayleigh lengths away from the NIR focus. Accordingly, the XUV pulses can be refocused to a small beam waist radius of 600 nm, enabling the absorption of up to four XUV photons by a single Ar atom in a setup that fits on a modest (2 m) laser table. Our concept represents a straightforward approach for the generation of intense XUV pulses in many laboratories, providing novel opportunities for XUV strong-field and nonlinear optics experiments, for XUV-pump XUV-probe spectroscopy and for the coherent diffractive imaging of nanoscale structures.