Novel genome-wide associations for effort valuation and psychopathology in children and adults.

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.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Time-resolved electron spectroscopy for chemical analysis of photodissociation: Photoelectron spectra of Fe(CO)5, Fe(CO)4, and Fe(CO)3.

The prototypical photoinduced dissociation of Fe(CO)5 in the gas phase is used to test time-resolved x-ray photoelectron spectroscopy for studying photochemical reactions. Upon one-photon excitation at 266 nm, Fe(CO)5 successively dissociates to Fe(CO)4 and Fe(CO)3 along a pathway where both fragments retain the singlet multiplicity of Fe(CO)5. The x-ray free-electron laser FLASH is used to probe the reaction intermediates Fe(CO)4 and Fe(CO)3 with time-resolved valence and core-level photoelectron spectroscopy, and experimental results are interpreted with ab initio quantum chemical calculations. Changes in the valence photoelectron spectra are shown to reflect changes in the valence-orbital interactions upon Fe-CO dissociation, thereby validating fundamental theoretical concepts in Fe-CO bonding. Chemical shifts of CO 3σ inner-valence and Fe 3p core-level binding energies are shown to correlate with changes in the coordination number of the Fe center. We interpret this with coordination-dependent charge localization and core-hole screening based on calculated changes in electron densities upon core-hole creation in the final ionic states. This extends the established capabilities of steady-state electron spectroscopy for chemical analysis to time-resolved investigations. It could also serve as a benchmark for how charge and spin density changes in molecular dissociation and excited-state dynamics are expressed in valence and core-level photoelectron spectroscopy.

Observation and Control of Laser-Enabled Auger Decay.

Single-photon laser-enabled Auger decay (spLEAD) is predicted theoretically [B. Cooper and V. Averbukh, Phys. Rev. Lett. 111, 083004 (2013)PRLTAO0031-900710.1103/PhysRevLett.111.083004] and here we report its first experimental observation in neon. Using coherent, bichromatic free-electron laser pulses, we detect the process and coherently control the angular distribution of the emitted electrons by varying the phase difference between the two laser fields. Since spLEAD is highly sensitive to electron correlation, this is a promising method for probing both correlation and ultrafast hole migration in more complex systems.

Circular Dichroism in Multiphoton Ionization of Resonantly Excited He

Intense, circularly polarized extreme-ultraviolet and near-infrared (NIR) laser pulses are combined to double ionize atomic helium via the oriented intermediate He^{+}(3p) resonance state. Applying angle-resolved electron spectroscopy, we find a large photon helicity dependence of the spectrum and the angular distribution of the electrons ejected from the resonance by NIR multiphoton absorption. The measured circular dichroism is unexpectedly found to vary strongly as a function of the NIR intensity. The experimental data are well described by theoretical modeling and possible mechanisms are discussed.

Communication: Direct evidence for sequential dissociation of gas-phase Fe(CO)5 via a singlet pathway upon excitation at 266 nm.

We prove the hitherto hypothesized sequential dissociation of Fe(CO)5 in the gas phase upon photoexcitation at 266 nm via a singlet pathway with time-resolved valence and core-level photoelectron spectroscopy with an x-ray free-electron laser. Valence photoelectron spectra are used to identify free CO molecules and to determine the time constants of stepwise dissociation to Fe(CO)4 within the temporal resolution of the experiment and further to Fe(CO)3 within 3 ps. Fe 3p core-level photoelectron spectra directly reflect the singlet spin state of the Fe center in Fe(CO)5, Fe(CO)4, and Fe(CO)3 showing that the dissociation exclusively occurs along a singlet pathway without triplet-state contribution. Our results are important for assessing intra- and intermolecular relaxation processes in the photodissociation dynamics of the prototypical Fe(CO)5 complex in the gas phase and in solution, and they establish time-resolved core-level photoelectron spectroscopy as a powerful tool for determining the multiplicity of transition metals in photochemical reactions of coordination complexes.

Infantile and childhood onset PLA2G6-associated neurodegeneration in a large North African cohort.

BACKGROUND AND PURPOSE: Mutations in the PLA2G6 gene are causative of PLA2G6-associated neurodegeneration (PLAN), a spectrum of neurodegenerative conditions including infantile, childhood and adult onset forms. METHODS: Seventeen North African patients with a clinical suspicion of infantile-onset PLAN underwent clinical, neurophysiological and neuroimaging examinations, and PLA2G6 sequencing. Haplotype analysis was performed to date the identified founder mutation. RESULTS: All patients carried biallelic mutations in PLA2G6. Sixteen children had the commonest form of infantile-onset PLAN, with early onset of psychomotor regression, hypotonia, pyramidal and cerebellar signs, and abnormal ocular movements. The phenotype was highly homogeneous, with rapid development of severe spastic tetraparesis, cognitive impairment and optic atrophy. Neuroimaging showed cerebellar atrophy and claval hypertrophy to be the commonest and earliest signs, whilst cerebellar cortex hyperintensity and pallidal iron deposition were later findings. Motor or sensory-motor neuropathy and electroencephalogram fast rhythms were also frequent. Nine patients from six families shared the same founder mutation (p.V691del) which probably arose by the late seventeenth century. Only one patient fitted the diagnosis of the much rarer childhood-onset PLAN. Despite the early onset (18 months), clinical progression was slower, with behavioral disturbances and dystonia. Typical features of infantile-onset PLAN such as hypotonia, nystagmus/strabismus, optic atrophy, electroencephalogram fast rhythms and motor neuropathy were absent. Cerebellar atrophy, claval hypertrophy and pallidal hypointensity were evident at brain magnetic resonance imaging. This patient carried a missense variant predicted to be less deleterious. CONCLUSIONS: The PLAN-associated phenotypes and the challenges of diagnosing the childhood-onset form are delineated, and a common North African founder mutation is identifed.

Novel collective autoionization process observed in electron spectra of He clusters.

The ionization dynamics of He nanodroplets irradiated with intense femtosecond extreme ultraviolet pulses of up to 1013 W/cm2 power density have been investigated by photoelectron spectroscopy. Helium droplets were resonantly excited to atomiclike 2p states with a photon energy of 21.4 eV, below the ionization potential (Ip), and directly into the ionization continuum with 42.8 eV photons. While electron emission following direct ionization above Ip is well explained within a model based on a sequence of direct electron emission events, the resonant excitation provides evidence of a new, collective ionization mechanism involving many excited atomiclike 2p states. With increasing power density the direct photoline due to an interatomic Coulombic decay disappears. It indicates that ionization occurs due to energy exchange between at least three excited atoms proceeding on a femtosecond time scale. In agreement with recent theoretical work the novel ionization process is very efficient and it is expected to be important for many other systems.

High resolution multiphoton spectroscopy by a tunable free-electron-laser light.

Seeded free electron lasers theoretically have the intensity, tunability, and resolution required for multiphoton spectroscopy of atomic and molecular species. Using the seeded free electron laser FERMI and a novel detection scheme, we have revealed the two-photon excitation spectra of dipole-forbidden doubly excited states in helium. The spectral profiles of the lowest (-1,0)(+1) (1)S(e) and (0,1)(0) (1)D(e) resonances display energy shifts in the meV range that depend on the pulse intensity. The results are explained by an effective two-level model based on calculated Rabi frequencies and decay rates.

AURA: Atlas of UTR Regulatory Activity.

SUMMARY: The Atlas of UTR Regulatory Activity (AURA) is a manually curated and comprehensive catalog of human mRNA untranslated regions (UTRs) and UTR regulatory annotations. Through its intuitive web interface, it provides full access to a wealth of information on UTRs that integrates phylogenetic conservation, RNA sequence and structure data, single nucleotide variation, gene expression and gene functional descriptions from literature and specialized databases. AVAILABILITY: http://aura.science.unitn.it CONTACT: aura@science.unitn.it; dassi@science.unitn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

HbA1c levels in patients with gestational diabetes mellitus: Relationship with pre-pregnancy BMI and pregnancy outcome.

BACKGROUND/AIMS: The use of glycated hemoglobin (HbA1c) measurement in gestational diabetes mellitus (GDM) is controversial. Aim of the present study was to determine HbA1c levels in a series of GDM patients, in order to verify the possible contribution of HbA1c to GDM management. MATERIALS/SUBJECTS AND METHODS: The study included 148 caucasian GDM patients. GDM screening was performed between the 24th and the 28th week of gestation by a two-step procedure, according to the 4th and 5th International Workshop Conference on Gestational Diabetes Mellitus recommendations. Exclusion criteria were: preexisting diabetes, corticosteroid therapy, history of asthma or hypertension, known fetal anomaly, history of previous stillbirth, preterm delivery considered to be likely for either maternal disease or fetal conditions. HBA1c was determined by a standard HPLC technique. RESULTS: At GDM diagnosis, all HbA1c levels were ≤ 6% and the greatest frequency (71/148; 48.0%) of HbA1c values resulted in the range 5.0-5.3%. This frequency increased to 54% before delivery. A significant correlation between HbA1c values at GDM diagnosis and individual BMI prior to conception was observed. The proportion of pregnancies presenting negative outcomes increased progressively with increasing HbA1c levels, from 6.2% (1/16) for HbA1c levels <5% to 18.3% (13/71) for HbA1c 5.0-5.3%, to 37.8% (17/45) in patients with HBA1c levels 5.4-5.6%, to 56.2% (9/16) for HbA1c levels >5.6%. ROC analysis showed that HbA1c at diagnosis and before delivery resulted a good predictor of adverse pregnancy outcome. CONCLUSIONS: The present results indicate that HbA1c levels could be of help in predicting adverse pregnancy events.

Controlling Fragmentation of the Acetylene Cation in the Vacuum Ultraviolet via Transient Molecular Alignment.

An open-loop control scheme of molecular fragmentation based on transient molecular alignment combined with single-photon ionization induced by a short-wavelength free electron laser (FEL) is demonstrated for the acetylene cation. Photoelectron spectra are recorded, complementing the ion yield measurements, to demonstrate that such control is the consequence of changes in the electronic response with molecular orientation relative to the ionizing field. We show that stable C2H2+ cations are mainly produced when the molecules are parallel or nearly parallel to the FEL polarization, while the hydrogen fragmentation channel (C2H2+ → C2H+ + H) predominates when the molecule is perpendicular to that direction, thus allowing one to distinguish between the two photochemical processes. The experimental findings are supported by state-of-the art theoretical calculations.

Isotope effects in dynamics of water isotopologues induced by core ionization at an x-ray free-electron laser.

Dynamical response of water exposed to x-rays is of utmost importance in a wealth of science areas. We exposed isolated water isotopologues to short x-ray pulses from a free-electron laser and detected momenta of all produced ions in coincidence. By combining experimental results and theoretical modeling, we identify significant structural dynamics with characteristic isotope effects in H2O2+, D2O2+, and HDO2+, such as asymmetric bond elongation and bond-angle opening, leading to two-body or three-body fragmentation on a timescale of a few femtoseconds. A method to disentangle the sequences of events taking place upon the consecutive absorption of two x-ray photons is described. The obtained deep look into structural properties and dynamics of dissociating water isotopologues provides essential insights into the underlying mechanisms.

Following excited-state chemical shifts in molecular ultrafast x-ray photoelectron spectroscopy.

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.

Electron-transfer-mediated decay and interatomic Coulombic decay from the triply ionized states in argon dimers.

We report the first observation of electron-transfer-mediated decay (ETMD) and interatomic Coulombic decay (ICD) from the triply charged states with an inner-valence vacancy, using the Ar dimer as an example. These ETMD and ICD processes, which lead to fragmentation of Ar(3+)-Ar into Ar(2+)-Ar(2+) and Ar(3+)-Ar+, respectively, are unambiguously identified by electron-ion-ion coincidence spectroscopy in which the kinetic energy of the ETMD or ICD electron and the kinetic energy release between the two fragment ions are measured in coincidence.

Photon-recoil imaging: Expanding the view of nonlinear x-ray physics.

Addressing the ultrafast coherent evolution of electronic wave functions has long been a goal of nonlinear x-ray physics. A first step toward this goal is the investigation of stimulated x-ray Raman scattering (SXRS) using intense pulses from an x-ray free-electron laser. Earlier SXRS experiments relied on signal amplification during pulse propagation through dense resonant media. By contrast, our method reveals the fundamental process in which photons from the primary radiation source directly interact with a single atom. We introduce an experimental protocol in which scattered neutral atoms rather than scattered photons are detected. We present SXRS measurements at the neon K edge and a quantitative theoretical analysis. The method should become a powerful tool in the exploration of nonlinear x-ray physics.

Concurrent chromothripsis events in a case of TP53 depleted acute myeloid leukemia with myelodysplasia-related changes.

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous hematological disorder defined by morphological, genetic, and clinical features. Patients with AML-MRC often show cytogenetic changes, which are associated with poor prognosis. Straightforward criteria for AML-MRC diagnosis and a more rigorous characterization of the genetic abnormalities accompanying this disease are needed. Here we describe an informative AML-MRC case, showing two separate, but concurrent, chromothripsis events, occurred at the onset of the tumor, and originating an unbalanced t(5;7) translocation and a derivative chromosome 12 with a highly rearranged short arm. Conversely, despite chromothripsis has been often associated with genomic amplification in cancer, in this case a large marker chromosome harboring amplified sequences from chromosomes 19 and 22 arose from a stepwise mechanism. Notably, the patient also showed a TP53 mutated status, known to be associated with an increased susceptibility towards chromothripsis and a poor prognosis. Our results indicate that multiple chromothripsis events may occur early in neoplastic transformation and act in a synergistic way with progressive chromosomal alterations to determine a dramatic impact on disease outcome, as suggested by the gene expression profile analysis.

Symmetry breakdown of electron emission in extreme ultraviolet photoionization of argon.

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.

Circular dichroism measurements at an x-ray free-electron laser with polarization control.

A non-destructive diagnostic method for the characterization of circularly polarized, ultraintense, short wavelength free-electron laser (FEL) light is presented. The recently installed Delta undulator at the LCLS (Linac Coherent Light Source) at SLAC National Accelerator Laboratory (USA) was used as showcase for this diagnostic scheme. By applying a combined two-color, multi-photon experiment with polarization control, the degree of circular polarization of the Delta undulator has been determined. Towards this goal, an oriented electronic state in the continuum was created by non-resonant ionization of the O2 1s core shell with circularly polarized FEL pulses at hν ≃ 700 eV. An also circularly polarized, highly intense UV laser pulse with hν ≃ 3.1 eV was temporally and spatially overlapped, causing the photoelectrons to redistribute into so-called sidebands that are energetically separated by the photon energy of the UV laser. By determining the circular dichroism of these redistributed electrons using angle resolving electron spectroscopy and modeling the results with the strong-field approximation, this scheme allows to unambiguously determine the absolute degree of circular polarization of any pulsed, ultraintense XUV or X-ray laser source.