Many advanced applications of X-ray free-electron lasers require pulse durations and time resolutions of only a few femtoseconds. To generate these pulses and to apply them in time-resolved ...experiments, synchronization techniques that can simultaneously lock all independent components, including all accelerator modules and all external optical lasers, to better than the delivered free-electron laser pulse duration, are needed. Here we achieve all-optical synchronization at the soft X-ray free-electron laser FLASH and demonstrate facility-wide timing to better than 30 fs r.m.s. for 90 fs X-ray photon pulses. Crucially, our analysis indicates that the performance of this optical synchronization is limited primarily by the free-electron laser pulse duration, and should naturally scale to the sub-10 femtosecond level with shorter X-ray pulses.
The ability to fully characterize ultrashort, ultra-intense X-ray pulses at free-electron lasers (FELs) will be crucial in experiments ranging from single-molecule imaging to extreme-timescale X-ray ...science. This issue is especially important at current-generation FELs, which are primarily based on self-amplified spontaneous emission and radiate with parameters that fluctuate strongly from pulse to pulse. Using single-cycle terahertz pulses from an optical laser, we have extended the streaking techniques of attosecond metrology to measure the temporal profile of individual FEL pulses with 5 fs full-width at half-maximum accuracy, as well as their arrival on a time base synchronized to the external laser to within 6 fs r.m.s. Optical laser-driven terahertz streaking can be utilized at any X-ray photon energy and is non-invasive, allowing it to be incorporated into any pump-probe experiment, eventually characterizing pulses before and after interaction with most sample environments.
The conversion of photon energy into other energetic forms in molecules is accompanied by charge moving on ultrafast timescales. We directly observe the charge motion at a specific site in an ...electronically excited molecule using time-resolved x-ray photoelectron spectroscopy (TR-XPS). We extend the concept of static chemical shift from conventional XPS by the excited-state chemical shift (ESCS), which is connected to the charge in the framework of a potential model. This allows us to invert TR-XPS spectra to the dynamic charge at a specific atom. We demonstrate the power of TR-XPS by using sulphur 2p-core-electron-emission probing to study the UV-excited dynamics of 2-thiouracil. The method allows us to discover that a major part of the population relaxes to the molecular ground state within 220-250 fs. In addition, a 250-fs oscillation, visible in the kinetic energy of the TR-XPS, reveals a coherent exchange of population among electronic states.
The Research Domain Criteria (RDoC) initiative was established by the US National Institute of Mental Health as a multilevel, disorder‐agnostic framework for analysis of human psychopathology through ...designated domains and constructs, including the “Positive Valence Systems” domain focused on reward‐related behavior. This study investigates the reward valuation subconstruct of “effort” and its association with genetic markers, functional neurobiological pathways, and polygenic risk scores for psychopathology in 1215 children aged 6–12 and their parents (n = 1044). All participants completed the effort expenditure for rewards task (EEfRT), which assesses “effort” according to two quantitative measures: hard‐task choice and reward sensitivity. Genetic association analyses were undertaken in MAGMA, utilizing EEfRT outcome variables as genome‐wide association studies phenotypes to compute SNP and gene‐level associations. Genome‐wide association analyses found two distinct genetic loci that were significantly associated with measures of reward sensitivity and a separate genetic locus associated with hard task choice. Gene‐set enrichment analysis yielded significant associations between “effort” and multiple gene sets involved in reward processing‐related pathways, including dopamine receptor signaling, limbic system and forebrain development, and biological response to cocaine. These results serve to establish “effort” as a relevant construct for understanding reward‐related behavior at the genetic level and support the RDoC framework for assessing disorder‐agnostic psychopathology.
Extreme ultraviolet and X-ray free-electron lasers (FELs) produce short-wavelength pulses with high intensity, ultrashort duration, well-defined polarization and transverse coherence, and have been ...utilized for many experiments previously possible only at long wavelengths: multiphoton ionization, pumping an atomic laser and four-wave mixing spectroscopy. However one important optical technique, coherent control, has not yet been demonstrated, because self-amplified spontaneous emission FELs have limited longitudinal coherence. Single-colour pulses from the FERMI seeded FEL are longitudinally coherent, and two-colour emission is predicted to be coherent. Here, we demonstrate the phase correlation of two colours, and manipulate it to control an experiment. Light of wavelengths 63.0 and 31.5 nm ionized neon, and we controlled the asymmetry of the photoelectron angular distribution by adjusting the phase, with a temporal resolution of 3 as. This opens the door to new short-wavelength coherent control experiments with ultrahigh time resolution and chemical sensitivity.
Short wavelength free-electron lasers (FELs), providing pulses of ultrahigh photon intensity, have revolutionized spectroscopy on ionic targets. Their exceptional photon flux enables multiple photon ...absorptions within a single femtosecond pulse, which in turn allows for deep insights into the photoionization process itself as well as into evolving ionic states of a target. Here we employ ultraintense pulses from the FEL FERMI to spectroscopically investigate the sequential emission of electrons from gaseous, atomic argon in the neutral as well as the ionic ground state. A pronounced forward-backward symmetry breaking of the angularly resolved emission patterns with respect to the light propagation direction is experimentally observed and theoretically explained for the region of the Cooper minimum, where the asymmetry of electron emission is strongly enhanced. These findings aim to originate a better understanding of the fundamentals of photon momentum transfer in ionic matter.
The nature of transient electronic states created by photoabsorption critically determines the dynamics of the subsequently evolving system. Here, we investigateK-shell photoionized atomic neon by ...absorbing a second photon within the Auger-decay lifetime of 2.4 fs using the European XFEL, a unique high-repetition-rate, wavelength-tunable x-ray free-electron laser. By high-resolution electron spectroscopy, we map out the transient Rydberg resonances unraveling the details of the subsequent decay of the hollow atom. So far, ultra-short-lived electronic transients, which are often inaccessible by experiments, were mainly inferred from theory but are now addressed by nonlinear x-ray absorption. The successful characterization of these resonances with femtosecond lifetimes provides the basis for a novel class of site-specific, nonlinear, and time-resolved studies with strong impact for a wide range of topics in physics and chemistry.
Background:Plasma endothelin-1 (ET-1) levels are increased in patients with systemic sclerosis (SSc), playing a central role in the development of fibrosis, vasoconstriction and inflammation1. While ...the beneficial effect of Bosentan, the endothelin receptor antagonists, have been demonstrated on vasoconstriction and fibrosis, its potential anti-inflammatory and immunomodulatory activity needs to be further investigated.Objectives:To assess whether Bosentan can modulate the gene expression profile of immune cells in sample of patients with limited and diffuse SSc and active digital ulcers.Methods:We enrolled 34 patients affected by SSc. Twenty-four patients were affected by limited SSc and 12 by diffuse SSc. Blood samples were collected from patients before and after 24 weeks of treatment with Bosentan, in the absence of immunosuppressive therapies. All patients received Bosentan 125 mg twice a day for 24 weeks. Gene expression profiles were assessed by GeneChip® Human Transcriptome Array 2.0 microarray technology. Significantly (p-value<0.05) and differentially (|FC|>1.5) expressed genes pre/post treatment were obtained by paired t-statistics, as implemented in Partek Genomics Suite ver. 6.6. These genes were subjected to functional enrichment analysis by Ingenuity Pathway Analysis. The effect of Bosentan on patients was studied on the “diffuse” and “limited” sub-cohorts, individually, as well as on the whole cohort.Results:Contrary to the limited cohort where differentially expressed genes resulted to be all non-coding genes which are almost all over-expressed before treatment, the diffuse cohort was characterized by 19 differentially expressed genes that enrich biological functions and pathways related to the immune system and its organic response (in particular T-cells). Comparing the limited to the diffuse cohort, pre- and post- treatment, a distinct genetic fingerprint emerges, that characterizes the response to Bosentan by the latter cohort as increased apoptosis of lymphocytes (z-score=3.28) and a decreased quantity of antigen presenting cells (from z-score=1.06 (pre) to -0.75 (post)).Conclusion:The presence of an inflammatory microenvironment, as occur in SSc, influence the relative expression of ET-1 receptors on immune cells, which in turn further contribute to the amplification of cellular responses to inflammation. The observed difference response to therapy between the two cohorts of patients was attributed to influence of ET-1 levels on the relative expression of ET-1 receptors on immune cells surface. Interestingly Bosentan, beside the already-known effect on promoting antigen presenting cells apoptosis, seem to exert its immunomodulatory activity also by deregulating functions that mainly involves the T cells and by promoting their apoptosis, which in turn reflect also its anti-inflammatory proprieties.References:1Tinazzi E, Puccetti A, Patuzzo G, et al. Endothelin receptors expressed by immune cells are involved in modulation of inflammation and in fibrosis: relevance to the pathogenesis of systemic sclerosis. J Immunol Res. 2015;2015:147616.Disclosure of Interests:None declared
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