CEP-stable high-energy ytterbium-doped fiber amplifier.

We report on the carrier-envelope phase (CEP) stabilization of a Yb-doped fiber amplifier system delivering 30 µJ pulses at 100 kHz repetition rate. A single-shot, every-shot measurement of the CEP stability based on a simple f-2f interferometer is performed, yielding a CEP standard deviation of 320 mrad rms over 1 s. Long-term stability is also assessed, with 380 mrad measured over 1 h. This level of performance is allowed by a hybrid architecture, including a passively CEP-stabilized front-end based on difference frequency generation and an active CEP stabilization loop for the fiber amplifier system, acting on a telecom-grade integrated LiNbO3 phase modulator. Together with recent demonstrations of temporal compression down to the few-cycle regime, the presented results demonstrate the relevance of the Yb-doped high repetition rate laser for attoscience.

Impact of noise in holography with extended references in the low signal regime.

Signal-to-noise ratio is a key factor in lensless imaging, particularly for low diffraction signal experiments in the single shot regime. We present our recent study of the noise impact on holography with extended references. Experimental data have been measured in single shot acquisition using an intense coherent soft X-ray high harmonic source. The impact of hardware and software noise under various detection conditions is discussed. A final comparison between single shot and multi-shot regimes is given.

Fourier transform holography with high harmonic spectra for attosecond imaging applications.

We demonstrate a method of using a Fourier holographic technique to utilize attosecond soft x-ray pulses to image nanometer-scale objects. A discrete frequency comb of laser-generated high-order harmonics, yielding a train of attosecond pulses, has been used to record spatially and spectrally resolved images. The individual wavelengths were also combined to form a single image, albeit with lower spatial resolution, demonstrating the applicability of the method to using isolated attosecond pulses with continuous bandwidths.

Shot-to-shot intensity and wavefront stability of high-harmonic generation.

We report on the shot-to-shot stability of intensity and spatial phase of high-harmonic generation (HHG). The intensity stability is measured for each high-harmonic (HH) order with a spectrometer. Additionally, the spatial phase is measured with an XUV wavefront sensor for a single HH order measured in a single shot, which according to our knowledge was not reported before with a Hartmann wavefront sensor. Furthermore, we compare the single-shot measurement of the spatial phase with time-integrated measurements and we show that the XUV wavefront sensor is a useful tool to simultaneously optimize the spatial phase and intensity of HHG within the available HHG parameter range used in this study.

Impact of wave front and coherence optimization in coherent diffractive imaging.

We present single shot nanoscale imaging using a table-top femtosecond soft X-ray laser harmonic source at a wavelength of 32 nm. We show that the phase retrieval process in coherent diffractive imaging critically depends on beam quality. Coherence and image fidelity are measured from single-shot coherent diffraction patterns of isolated nano-patterned slits. Impact of flux, wave front and coherence of the soft X-ray beam on the phase retrieval process and the image quality are discussed. After beam improvements, a final image reconstruction is presented with a spatial resolution of 78 nm (half period) in a single 20 fs laser harmonic shot.

X-ray generation by fs-laser processing of biological material.

The use of ultrashort pulse lasers in medical treatments is increasing and is already an essential tool, particularly in the treatment of eyes, bones and skin. One of the main advantages of laser treatment is that it is fast and minimally invasive. Due to the interaction of ultrashort laser pulses with matter, X-rays can be generated during the laser ablation process. This is important not only for the safety of the patient, but also for the practitioner to ensure that the legally permissible dose is not exceeded. Although our results do not raise safety concerns for existing clinical applications, they might impact future developments at higher peak powers. In order to provide guidance to laser users in the medical field, this paper examines the X-ray emission spectra and dose of several biological materials and describes their dependence on the laser pulse energy.

Histopathological features in fatal COVID-19 acute respiratory distress syndrome.

Background: COVID-19 acute respiratory distress syndrome (ARDS) shares the common histological hallmarks with other forms of ARDS. However, the chronology of the histological lesions has not been well established. Objective: To describe the chronological histopathological alterations in the lungs of patients with COVID-19 related ARDS. Design: A prospective cohort study was carried out. Setting: Intensive Care Unit of a tertiary hospital. Patients: The first 22 consecutive COVID-19 deaths. Measurements: Lung biopsies and histopathological analyses were performed in deceased patients with COVID-19 related ARDS. Clinical data and patient course were evaluated. Results: The median patient age was 66 [63-74] years; 73% were males. The median duration of mechanical ventilation was 17 [8-24] days. COVID-19 induced pulmonary injury was characterized by an exudative phase in the first week of the disease, followed by a proliferative/organizing phase in the second and third weeks, and finally an end-stage fibrosis phase after the third week. Viral RNA and proteins were detected in pneumocytes and macrophages in a very early stage of the disease, and were no longer detected after the second week. Limitation: Limited sample size. Conclusions: The chronological evolution of COVID-19 lung histopathological lesions seems to be similar to that seen in other forms of ARDS. In particular, lung lesions consistent with potentially corticosteroid-sensitive lesions are seen.

Antecedentes: El síndrome de dificultad respiratoria aguda (SDRA) asociado a la COVID-19 comparte características histológicas con otros tipos de SDRA. Sin embargo, no se ha establecido adecuadamente la cronología de las lesiones histológicas. Objetivo: Describir las alteraciones histopatológicas cronológicas en los pulmones de los pacientes con síndrome de dificultad respiratoria aguda asociado a COVID-19. Diseño: Estudio prospectivo de cohortes. Ámbito: Unidad de cuidados intensivos de un hospital terciario. Pacientes: Las primeras 22 muertes consecutivas por COVID-19. Intervenciones: Se llevaron a cabo biopsias pulmonares y análisis histopatológicos en pacientes fallecidos por SDRA asociado a COVID-19. Se evaluaron los datos clínicos y la evolución médica. Resultados: La mediana de edad de los pacientes fue de 66 (63-74) años y el 73% eran varones. La mediana de la duración de la ventilación mecánica fue de 17 (8-24) días. La lesión pulmonar inducida por COVID-19 se caracterizó por una fase exudativa durante la primera semana de la enfermedad, seguida de una fase proliferativa/organizativa en la segunda y tercera semana y, por último, una fase de fibrosis en fase terminal tras la tercera semana de evolución. Se detectaron proteínas y ARN vírico en neumocitos y macrófagos en una fase muy temprana de la enfermedad, pero estos ya no se volvieron a detectar a partir de la segunda semana. Limitación: Tamaño limitado de la muestra. Conclusión: La evolución cronológica de las lesiones histopatológicas pulmonares asociadas a la COVID-19 parece ser similar a la de otras formas de SDRA. En particular, se observan daños pulmonares coherentes con las lesiones potencialmente sensibles a los corticosteroides.

Histopathological features in fatal COVID-19 acute respiratory distress syndrome.

BACKGROUND: COVID-19 acute respiratory distress syndrome (ARDS) shares the common histological hallmarks with other forms of ARDS. However, the chronology of the histological lesions has not been well established. OBJECTIVE: To describe the chronological histopathological alterations in the lungs of patients with COVID-19 related ARDS. DESIGN: A prospective cohort study was carried out. SETTING: Intensive Care Unit of a tertiary hospital. PATIENTS: The first 22 consecutive COVID-19 deaths. MEASUREMENTS: Lung biopsies and histopathological analyses were performed in deceased patients with COVID-19 related ARDS. Clinical data and patient course were evaluated. RESULTS: The median patient age was 66 [63-74] years; 73% were males. The median duration of mechanical ventilation was 17 [8-24] days. COVID-19 induced pulmonary injury was characterized by an exudative phase in the first week of the disease, followed by a proliferative/organizing phase in the second and third weeks, and finally an end-stage fibrosis phase after the third week. Viral RNA and proteins were detected in pneumocytes and macrophages in a very early stage of the disease, and were no longer detected after the second week. LIMITATION: Limited sample size. CONCLUSIONS: The chronological evolution of COVID-19 lung histopathological lesions seems to be similar to that seen in other forms of ARDS. In particular, lung lesions consistent with potentially corticosteroid-sensitive lesions are seen.

Time-resolved pump-probe experiments at the LCLS.

The first time-resolved x-ray/optical pump-probe experiments at the SLAC Linac Coherent Light Source (LCLS) used a combination of feedback methods and post-analysis binning techniques to synchronize an ultrafast optical laser to the linac-based x-ray laser. Transient molecular nitrogen alignment revival features were resolved in time-dependent x-ray-induced fragmentation spectra. These alignment features were used to find the temporal overlap of the pump and probe pulses. The strong-field dissociation of x-ray generated quasi-bound molecular dications was used to establish the residual timing jitter. This analysis shows that the relative arrival time of the Ti:Sapphire laser and the x-ray pulses had a distribution with a standard deviation of approximately 120 fs. The largest contribution to the jitter noise spectrum was the locking of the laser oscillator to the reference RF of the accelerator, which suggests that simple technical improvements could reduce the jitter to better than 50 fs.

Single-shot femtosecond x-ray holography using extended references.

In the context of x-ray lensless imaging, we present a recent approach for Fourier transform holography based on the use of extended references. Major advances shown here rely on a high signal efficiency and on the direct image reconstruction of the object performed by a simple linear derivative. Moreover, the extended holographic reference is easy to manufacture and can be applied to a variety of imaging experiments. Here we demonstrate single-shot imaging with a table-top, laser-based coherent soft x-ray source. A spatial resolution of 110 nm was obtained with an integration time of 20 fs.

Auger electron angular distribution of double core-hole states in the molecular reference frame.

The Linac Coherent Light Source free electron laser is a source of high brightness x rays, 2×10(11) photons in a ∼5 fs pulse, that can be focused to produce double core vacancies through rapid sequential ionization. This enables double core vacancy Auger electron spectroscopy, an entirely new way to study femtosecond chemical dynamics with Auger electrons that probe the local valence structure of molecules near a specific atomic core. Using 1.1 keV photons for sequential x-ray ionization of impulsively aligned molecular nitrogen, we observed a rich single-site double core vacancy Auger electron spectrum near 413 eV, in good agreement with ab initio calculations, and we measured the corresponding Auger electron angle dependence in the molecular frame.

A high-intensity highly coherent soft X-ray femtosecond laser seeded by a high harmonic beam.

Synchrotrons have for decades provided invaluable sources of soft X-rays, the application of which has led to significant progress in many areas of science and technology. But future applications of soft X-rays--in structural biology, for example--anticipate the need for pulses with much shorter duration (femtoseconds) and much higher energy (millijoules) than those delivered by synchrotrons. Soft X-ray free-electron lasers should fulfil these requirements but will be limited in number; the pressure on beamtime is therefore likely to be considerable. Laser-driven soft X-ray sources offer a comparatively inexpensive and widely available alternative, but have encountered practical bottlenecks in the quest for high intensities. Here we establish and characterize a soft X-ray laser chain that shows how these bottlenecks can in principle be overcome. By combining the high optical quality available from high-harmonic laser sources (as a seed beam) with a highly energetic soft X-ray laser plasma amplifier, we produce a tabletop soft X-ray femtosecond laser operating at 10 Hz and exhibiting full saturation, high energy, high coherence and full polarization. This technique should be readily applicable on all existing laser-driven soft X-ray facilities.

Internal frequency conversion extreme ultraviolet interferometer using mutual coherence properties of two high-order-harmonic sources.

We report on an innovative two-dimensional imaging extreme ultraviolet (XUV) interferometer operating at 32 nm based on the mutual coherence of two laser high order harmonics (HOH) sources, separately generated in gas. We give the first evidence that the two mutually coherent HOH sources can be produced in two independent spatially separated gas jets, allowing for probing centimeter-sized objects. A magnification factor of 10 leads to a micron resolution associated with a subpicosecond temporal resolution. Single shot interferograms with a fringe visibility better than 30% are routinely produced. As a test of the XUV interferometer, we measure a maximum electronic density of 3x10(20) cm(-3) 1.1 ns after the creation of a plasma on aluminum target.

Single-shot diffractive imaging with a table-top femtosecond soft x-ray laser-harmonics source.

Coherent x-ray diffractive imaging is a powerful method for studies on nonperiodic structures on the nanoscale. Access to femtosecond dynamics in major physical, chemical, and biological processes requires single-shot diffraction data. Up to now, this has been limited to intense coherent pulses from a free electron laser. Here we show that laser-driven ultrashort x-ray sources offer a comparatively inexpensive alternative. We present measurements of single-shot diffraction patterns from isolated nano-objects with a single 20 fs pulse from a table-top high-harmonic x-ray laser. Images were reconstructed with a resolution of 119 nm from the single shot and 62 nm from multiple shots.

Demonstration of a spatial filtering amplifier for high-order harmonics.

We report what is to our knowledge the first demonstration of spatial filtering of a high-order harmonic beam into a soft-x-ray laser plasma amplifier at 32.8 nm. After amplification the seed energy is enhanced by a factor of 50, and the beam profile of the amplified beam exhibits an Airy-like shape due to the spatial filtering by the optical field ionized plasma. Moreover, the transverse coherence of the spatially filtered amplified beam is strongly enhanced, resulting in the generation of a peak coherent power of 0.9 x 10(5) to 1.8 x 10(5) W.

High harmonic XUV spectral phase interferometry for direct electric-field reconstruction.

We demonstrate the first experimental complete temporal characterization of high-harmonic XUV pulses by spectral phase interferometry, with an all-optical setup. This method allows us to perform single-shot measurements of the harmonic temporal profile and phase, revealing a remarkable shot-to-shot stability. We characterize harmonics generated in argon by a 50 fs 800 nm laser pulse. The 11th harmonic is found to be 22 fs long with a negative chirp rate of -4.8 x 10(27) s(-2). This duration can be reduced to 13 fs by modulating the polarization of the generating laser. The technique is easy to implement and could be routinely used in femtosecond XUV pump-probe experiments with harmonics.

Extreme ultraviolet Fourier-transform spectroscopy with high order harmonics.

We demonstrate a new scheme for extreme ultraviolet (xuv) Fourier-transform spectroscopy based on the generation of two phase-locked high-harmonic beams. It allows us to measure for the first time interferograms at wavelengths as short as 90 nm, and open the perspective of performing high-resolution Fourier-transform absorption spectroscopy in the xuv. Our measurements also demonstrate that a precise control of the relative phase of harmonic pulses can be obtained with an accuracy on an attosecond time scale, of importance for future xuv pump-xuv probe attosecond spectroscopy.