Simulation of spatiotemporal light dynamics based on the time-dependent Schrödinger equation.

We establish a first-principle model for the simulation of spatiotemporal light pulse dynamics based on the combination of the time-dependent Schrödinger equation and the unidirectional propagation equation. The proposed numerical scheme enables computationally efficient simulation while being stable and accurate. We use the new model to examine self-focusing of a short pulse in atomic hydrogen and show that an accurate description of the excited-levels dynamics can only be achieved by a propagation model with an ab-initio description of the light-matter interaction, which accounts for the laser-dressed multilevel structure of the system, including bound and free states, and its sub-cycle response.

Single-cell metabolic profiling reveals subgroups of primary human hepatocytes with heterogeneous responses to drug challenge.

BACKGROUND: Xenobiotics are primarily metabolized by hepatocytes in the liver, and primary human hepatocytes are the gold standard model for the assessment of drug efficacy, safety, and toxicity in the early phases of drug development. Recent advances in single-cell genomics demonstrate liver zonation and ploidy as main drivers of cellular heterogeneity. However, little is known about the impact of hepatocyte specialization on liver function upon metabolic challenge, including hepatic metabolism, detoxification, and protein synthesis. RESULTS: Here, we investigate the metabolic capacity of individual human hepatocytes in vitro. We assess how chronic accumulation of lipids enhances cellular heterogeneity and impairs the metabolisms of drugs. Using a phenotyping five-probe cocktail, we identify four functional subgroups of hepatocytes responding differently to drug challenge and fatty acid accumulation. These four subgroups display differential gene expression profiles upon cocktail treatment and xenobiotic metabolism-related specialization. Notably, intracellular fat accumulation leads to increased transcriptional variability and diminishes the drug-related metabolic capacity of hepatocytes. CONCLUSIONS: Our results demonstrate that, upon a metabolic challenge such as exposure to drugs or intracellular fat accumulation, hepatocyte subgroups display different and heterogeneous transcriptional responses.

epiAneufinder identifies copy number alterations from single-cell ATAC-seq data.

Single-cell open chromatin profiling via scATAC-seq has become a mainstream measurement of open chromatin in single-cells. Here we present epiAneufinder, an algorithm that exploits the read count information from scATAC-seq data to extract genome-wide copy number alterations (CNAs) for individual cells, allowing the study of CNA heterogeneity present in a sample at the single-cell level. Using different cancer scATAC-seq datasets, we show that epiAneufinder can identify intratumor clonal heterogeneity in populations of single cells based on their CNA profiles. We demonstrate that these profiles are concordant with the ones inferred from single-cell whole genome sequencing data for the same samples. EpiAneufinder allows the inference of single-cell CNA information from scATAC-seq data, without the need of additional experiments, unlocking a layer of genomic variation which is otherwise unexplored.

Ultrafast Hidden Spin Polarization Dynamics of Bright and Dark Excitons in 2H-WSe_{2}.

We performed spin-, time- and angle-resolved extreme ultraviolet photoemission spectroscopy of excitons prepared by photoexcitation of inversion-symmetric 2H-WSe_{2} with circularly polarized light. The very short probing depth of XUV photoemission permits selective measurement of photoelectrons originating from the top-most WSe_{2} layer, allowing for direct measurement of hidden spin polarization of bright and momentum-forbidden dark excitons. Our results reveal efficient chiroptical control of bright excitons' hidden spin polarization. Following optical photoexcitation, intervalley scattering between nonequivalent K-K^{'} valleys leads to a decay of bright excitons' hidden spin polarization. Conversely, the ultrafast formation of momentum-forbidden dark excitons acts as a local spin polarization reservoir, which could be used for spin injection in van der Waals heterostructures involving multilayer transition metal dichalcogenides.

Non-instantaneous third-order optical response of gases in low-frequency fields.

It is commonly assumed that for low-intensity short optical pulses far from resonance, the third-order optical nonlinear response is instantaneous. We solve the three-dimensional time-dependent Schrödinger equation for the hydrogen atom and show that this is not the case: the polarization is not simply proportional to the cube of the electric field even at low intensities. We analyze the fundamental-frequency and third-harmonic nonlinear susceptibilities of hydrogen, investigate their dependence on intensity, and find that the delays in the Kerr response rapidly approach the femtosecond time-scale at higher intensities, while the delays in the third harmonic generation remain much lower. We also propose an experimental scheme to detect and characterize the above effects.

Electronic State Population Dynamics upon Ultrafast Strong Field Ionization and Fragmentation of Molecular Nitrogen.

Air lasing from single ionized N_{2}^{+} molecules induced by laser filamentation in air has been intensively investigated and the mechanisms responsible for lasing are currently highly debated. We use ultrafast nitrogen K-edge spectroscopy to follow the strong field ionization and fragmentation dynamics of N_{2} upon interaction with an ultrashort 800 nm laser pulse. Using probe pulses generated by extreme high-order harmonic generation, we observe transitions indicative of the formation of the electronic ground X^{2}Σ_{g}^{+}, first excited A^{2}Π_{u}, and second excited B^{2}Σ_{u}^{+} states of N_{2}^{+} on femtosecond timescales, from which we can quantitatively determine the time-dependent electronic state population distribution dynamics of N_{2}^{+}. Our results show a remarkably low population of the A^{2}Π_{u} state, and nearly equal populations of the X^{2}Σ_{g}^{+} and B^{2}Σ_{u}^{+} states. In addition, we observe fragmentation of N_{2}^{+} into N and N^{+} on a timescale of several tens of picoseconds that we assign to significant collisional dynamics in the plasma, resulting in dissociative excitation of N_{2}^{+}.

Propagator operator for pulse propagation in resonant media.

We show that, for the case of resonant media, the available models for unidirectional propagation of short pulses can face serious challenges with respect to numerical efficiency, accuracy, or numerical artifacts. We propose an alternative approach based on a propagator operator defined in the time domain. This approach enables precise simulations using short time windows even for resonant media and facilitates coupling of the propagation equation with first-principle methods such as the time-dependent Schödinger equation. Additionally, we develop a numerically efficient recipe to construct and apply such a propagator operator.

EpiScanpy: integrated single-cell epigenomic analysis.

EpiScanpy is a toolkit for the analysis of single-cell epigenomic data, namely single-cell DNA methylation and single-cell ATAC-seq data. To address the modality specific challenges from epigenomics data, epiScanpy quantifies the epigenome using multiple feature space constructions and builds a nearest neighbour graph using epigenomic distance between cells. EpiScanpy makes the many existing scRNA-seq workflows from scanpy available to large-scale single-cell data from other -omics modalities, including methods for common clustering, dimension reduction, cell type identification and trajectory learning techniques, as well as an atlas integration tool for scATAC-seq datasets. The toolkit also features numerous useful downstream functions, such as differential methylation and differential openness calling, mapping epigenomic features of interest to their nearest gene, or constructing gene activity matrices using chromatin openness. We successfully benchmark epiScanpy against other scATAC-seq analysis tools and show its outperformance at discriminating cell types.

Common Ground Information Affects Reference Resolution: Evidence From Behavioral Data, ERPs, and Eye-Tracking.

One of the most important social cognitive skills in humans is the ability to "put oneself in someone else's shoes," that is, to take another person's perspective. In socially situated communication, perspective taking enables the listener to arrive at a meaningful interpretation of what is said (sentence meaning) and what is meant (speaker's meaning) by the speaker. To successfully decode the speaker's meaning, the listener has to take into account which information he/she and the speaker share in their common ground (CG). We here further investigated competing accounts about when and how CG information affects language comprehension by means of reaction time (RT) measures, accuracy data, event-related potentials (ERPs), and eye-tracking. Early integration accounts would predict that CG information is considered immediately and would hence not expect to find costs of CG integration. Late integration accounts would predict a rather late and effortful integration of CG information during the parsing process that might be reflected in integration or updating costs. Other accounts predict the simultaneous integration of privileged ground (PG) and CG perspectives. We used a computerized version of the referential communication game with object triplets of different sizes presented visually in CG or PG. In critical trials (i.e., conflict trials), CG information had to be integrated while privileged information had to be suppressed. Listeners mastered the integration of CG (response accuracy 99.8%). Yet, slower RTs, and enhanced late positivities in the ERPs showed that CG integration had its costs. Moreover, eye-tracking data indicated an early anticipation of referents in CG but an inability to suppress looks to the privileged competitor, resulting in later and longer looks to targets in those trials, in which CG information had to be considered. Our data therefore support accounts that foresee an early anticipation of referents to be in CG but a rather late and effortful integration if conflicting information has to be processed. We show that both perspectives, PG and CG, contribute to socially situated language processing and discuss the data with reference to theoretical accounts and recent findings on the use of CG information for reference resolution.

Imaging plasma formation in isolated nanoparticles with ultrafast resonant scattering.

We have recorded the diffraction patterns from individual xenon clusters irradiated with intense extreme ultraviolet pulses to investigate the influence of light-induced electronic changes on the scattering response. The clusters were irradiated with short wavelength pulses in the wavelength regime of different 4d inner-shell resonances of neutral and ionic xenon, resulting in distinctly different optical properties from areas in the clusters with lower or higher charge states. The data show the emergence of a transient structure with a spatial extension of tens of nanometers within the otherwise homogeneous sample. Simulations indicate that ionization and nanoplasma formation result in a light-induced outer shell in the cluster with a strongly altered refractive index. The presented resonant scattering approach enables imaging of ultrafast electron dynamics on their natural timescale.

Ultrafast imaging of laser-controlled non-adiabatic dynamics in NO2 from time-resolved photoelectron emission.

Time-resolving and controlling coupled electronic and nuclear dynamics at conical intersections on the sub-femtosecond to few-femtosecond time scale is among the challenging goals of attosecond physics. Here we present numerical simulations of time-resolved photoelectron spectroscopy of such dynamics in NO2, where the coupled electron-nuclear motion at the 2A1/2B2 conical intersection is steered on the sub-laser-cycle time scale by a nearly single-cycle, waveform controlled mid-infrared laser pulse. For a rigorous description of the photoionization dynamics, we employ ab initio energy- and geometry-resolved photoionization matrix elements obtained with the multichannel R-matrix method, using a multiconfigurational description of the molecule and a newly developed algorithm to generate photoionization dipoles that are phase consistent on the level of both the neutral and the ionic states. We find that for sufficient molecular alignment, the time- and energy-resolved anisotropy parameters of the photoelectron angular distributions provide a particularly clear picture of both the ultrafast natural molecular dynamics at the conical intersection and its modifications by the control pulse. In particular, changes in the electronic and nuclear configurations induced by the control pulse lead to the appearance of non-vanishing odd anisotropy parameters in the photoelectron spectra. These are absent in the spectra obtained without the control pulse and therefore provide sensitive, background-free diagnostic of the control.

Amplification of intense light fields by nearly free electrons.

Light can be used to modify and control properties of media, as in the case of electromagnetically induced transparency or, more recently, for the generation of slow light or bright coherent XUV and X-ray radiation. Particularly unusual states of matter can be created by light fields with strengths comparable to the Coulomb field that binds valence electrons in atoms, leading to nearly-free electrons oscillating in the laser field and yet still loosely bound to the core [1,2]. These are known as Kramers-Henneberger states [3], a specific example of laser-dressed states [2]. Here, we demonstrate that these states arise not only in isolated atoms [4,5], but also in rare gases, at and above atmospheric pressure, where they can act as a gain medium during laser filamentation. Using shaped laser pulses, gain in these states is achieved within just a few cycles of the guided field. The corresponding lasing emission is a signature of population inversion in these states and of their stability against ionization. Our work demonstrates that these unusual states of neutral atoms can be exploited to create a general ultrafast gain mechanism during laser filamentation.

Validation of the Self-Curiosity Attitude-Interest Scale in Colombia / Validación de la Escala de Self-Curiosity Attitude-Interest en Colombia

Abstract This paper presents a theoretical review of the psychological construct of human curiosity and the Colombian version of the Self-Curiosity Attitude-Interest Scale. This is a two-factor self-report scale that assesses the attitude and the interest that people have to explore their own inner world. Two paired samples for gender, age and working class of Colombian (n = 170) and Italian (n = 195) participants (N = 365) were included in the study. Confirmatory Factor Analysis revealed a good fit of the data to the two-factor model of the Self-Curiosity Attitude-Interest Scale in Italian and Colombian subjects (respectively, x 2(13) =16.073, p = .245 and x 2(13) =10.352, p = .665). Also, Measurement Invariance Analysis suggested equivalent factor structures (Configurai Invariance, x 2 (26) = 26.423, p = .440) and factor loadings across the two groups (Metric Invariance, x 2 (31) = 34.242, p = .315). The results do not support scalar invariance (x 2 (38) = 82.058, p < .001). Data suggest concurrent validity of the Self-Curiosity Attitude-Interest in the Colombian group, welding evidence for the scale application in the Colombian context. In conclusion, the results posit that the two-factor model of the Self-Curiosity Attitude-Interest Scale is adequate in Colombia; the psychological construct of self-curiosity is conceived similarly in Colombia and in Italy, and the scale has expected correlations with other relevant psychological constructs.

Resumen El objetivo de este estudio es presentar una revisión teórica del constructo psicológico de la curiosidad humana, así como presentar la validación de la versión colombiana de la Self-Curiosity Attitude-Interest Scale, una escala de auto-reporte de dos factores que evalúa la actitud y el interés que la gente posee para explorar su propio mundo interior. Se incluyeron en el estudio participantes (N = 365) Colombianos (n = 170) e Italianos (n = 195) pareados por género, edad y clase trabajadora. El Análisis Factorial Confirmatorio ha revelado un buen ajuste de los datos al modelo de dos factores de Self-Curiosity Attitude-Interest Scale en participantes italianos y colombianos (respectivamente, x 2(13) =16.073, p = .245 y x 2(13) =10.352, p = .665). El Análisis de Invariancia ha sugerido factores de estructuras (Invariancia de Configuración, x 2 (26) = 26.423, p = .440) y pesos de los factores equivalentes entre los dos grupos (Invariancia Métrica, x 2 (31) = 34.242, p = .315). Los datos no soportan la Invariancia Escalar (x 2 (38) = 82.058, p < .001). Adicionalmente, los datos destacaron la validez concurrente de la escala en el grupo de Colombia, y la posibilidad de aplicar la escala en el contexto colombiano. En conclusión, los resultados demuestran que el modelo de dos factores de la Self-Curiosity Attitude-Interest Scale es apto para ser aplicado en Colombia, así mismo reflejan que el concepto psicológico de la self-curiosity es concebido de forma similar tanto en Colombia como en Italia, y que la escala indica correlaciones con otras construcciones psicológicas relevantes.

Impact of associative word learning on phonotactic processing in 6-month-old infants: A combined EEG and fNIRS study.

During early language development native phonotactics are acquired in a 'bottom-up' fashion, relying on exquisite auditory differentiation skills operational from birth. Since basic lexico-semantic abilities have been demonstrated from 6 months onwards, 'top-down' influences on phonotactic learning may complement the extraction of transitional probabilities in phonotactic learning. Such a bidirectional acquisition strategy predicts, that familiarization with (proto)words should affect processing of untrained word-forms of similar phonological structure. We investigated 6-month-old infants undergoing an associative training to establish a pseudoword-pseudoobject link. Comparison between pre- and post-training responses to trained and untrained items allowed investigating training effects. Additionally phonotactic status (50% legal, 50% illegal with regard to German) allowed investigating influences of previous language experience. EEG and functional near-infrared spectroscopy (fNIRS) provided measures of electrophysiological and hemodynamic responses. We find evidence for a robust effect of associative training on pseudoword processing when presented in isolation. This transferred to untrained items. Previous linguistic experience showed a much weaker effect. Taken together the results suggest that sensitivity to phonotactic contrasts is present at 6 months, but that acceptance as lexical candidates is rapidly modulated when word forms following non-native phonotactics become potentially meaningful due to repeated exposure in a semantic context.

The viral envelope is not sufficient to transfer the unique broad cell tropism of Bungowannah virus to a related pestivirus.

Bungowannah virus is the most divergent pestivirus, and both origin and reservoir host have not been identified so far. We therefore performed in vitro tropism studies, which showed that Bungowannah virus differs remarkably from other pestiviruses. Interestingly, cell lines of vervet monkey, mouse, human and even of bat origin were susceptible. This broad in vitro tropism was not observed for a chimeric bovine viral diarrhoea virus (BVDV) expressing all structural proteins of Bungowannah virus. The viral envelope was not sufficient to completely transfer the cell tropism of Bungowannah virus to another pestivirus, and viral RNA replication was either markedly reduced or not detectable in a number of different cell lines for the tested BVDV strain and the chimera. We therefore suggest that the replication machinery together with the viral envelope is responsible for the unique broad cell tropism of Bungowannah virus.

Pain-related and negative semantic priming enhances perceived pain intensity.

BACKGROUND: Negative affective and pain-related cues, such as pictures or words, have been shown to act as primes and enhance the perceived intensity of subsequent painful events. For pain-related semantic primes, it remains unclear whether this effect depends on negative valence itself or, specifically, on the pain-relatedness of the words. OBJECTIVES: To investigate the effect of pain-related, negative affective (pain-unrelated) and neutral semantic primes on the perception of subsequent noxious target stimuli. METHODS: Pain ratings in response to noxious electrical stimulation of light and moderate intensity were examined in 39 healthy subjects after subjects were exposed to semantic primes of different meaning and valence (pain-related, negative, positive and neutral adjectives) presented with different interstimulus intervals (0 ms, 500 ms and 1500 ms). RESULTS: Increased pain ratings of noxious stimuli were observed following pain-related and negative compared with neutral primes. DISCUSSION: The results support the motivational priming theory for semantic stimuli, indicating that affectively negative semantic primes increase subjective pain intensity. However, a specific pain-related priming effect was not reliably demonstrated. Additionally, it is shown that experimental parameters (ie, stimulus intensity and interstimulus interval) modify the extent of negative and pain-related semantic priming. CONCLUSIONS: Verbal priming plays a role for the perception of noxious stimuli in a time-dependent manner.

N pro of Bungowannah virus exhibits the same antagonistic function in the IFN induction pathway than that of other classical pestiviruses.

Bungowannah virus is the most divergent atypical pestivirus that had been detected up to now, and does not fit into any of the four approved species: Bovine viral diarrhea virus type 1 (BVDV-1) and type 2 (BVDV-2), Classical swine fever virus (CSFV) and Border disease virus (BDV). However, the presence of N(pro) and E(rns) coding regions, which are unique to pestiviruses, provides clear evidence of a pestivirus. Nevertheless, the amino acid identity of Bungowannah virus N(pro) and BVDV-1 N(pro) (strain CP7) is only 51.5%. By using a BVDV-1 backbone, a novel chimeric construct was generated, in which the genomic region encoding the non-structural protein N(pro) was replaced by that of Bungowannah virus (CP7_N(pro)-Bungo). In vitro studies of CP7_N(pro)-Bungo revealed autonomous replication with the same efficacy as the BVDV backbone CP7 and infectious high-titer virus could be collected. In order to compare the ability of interferon (IFN) suppression, two reporter gene assays, specific for type-I IFN, were carried out. In virus-infected cells, no significant difference in blocking of IFN expression between the parental virus CP7, Bungowannah virus and the chimeric construct CP7_N(pro)-Bungo could be detected. In contrast, an N(pro) deletion mutant showed an impaired replication in bovine cells and a marked type-I IFN response. Taken together, our findings reveal the compatibility of non-structural protein N(pro) of atypical Bungowannah virus with a BVDV type 1 backbone and its characteristic feature as an inhibitor of type-I IFN induction with an inhibitor-activity comparable to other pestiviruses.

Fully automatic CAD design of the occlusal morphology of partial crowns compared to dental technicians' design.

OBJECTIVES: The aim of this study was to compare the occlusal morphology of partial crown reconstructions made by dental technicians with reconstructions made by a fully automatic software process (biogeneric tooth model) in relation to the original natural tooth shape. MATERIAL AND METHODS: Stone replicas of natural teeth were measured three-dimensionally before preparing inlay and onlay cavities for ceramic restorations (n = 5). For each preparation, five reconstructions (in total n = 25) were made by five dental technicians. Additionally, reconstructions were calculated automatically by a software based on the biogeneric tooth model (Cerec 3D). In order to compare the two different kinds of reconstruction, an objective metrical similarity measure (shape similarity value, SSV) based on calculated volumes between compared datasets was used. RESULTS: In 22 of 25 cases, the reconstructions made by the CAD software were closer to the original situation than the reconstructions made by the technicians. Mean average SSV of reconstructions made by the technicians (310.2 ± 78.8 µm) was significantly higher (p < 0.05) than mean SSV of CAD reconstructions (biogeneric model) (222.0 ± 47.7 µm). CONCLUSIONS: In the design of naturally shaped occlusal inlay/onlay surfaces, a fully automatic CAD system can be at least as good as conventional wax-ups by dental technicians. CLINICAL RELEVANCE: The adjustment of a dental restoration to fit the morphology of surrounding tooth structures, still presents challenges for the dentist.

Imaging the Kramers-Henneberger atom.

Today laser pulses with electric fields comparable to or higher than the electrostatic forces binding valence electrons in atoms and molecules have become a routine tool with applications in laser acceleration of electrons and ions, generation of short wavelength emission from plasmas and clusters, laser fusion, etc. Intense fields are also naturally created during laser filamentation in the air or due to local field enhancements in the vicinity of metal nanoparticles. One would expect that very intense fields would always lead to fast ionization of atoms or molecules. However, recently observed acceleration of neutral atoms [Eichmann et al. (2009) Nature 461:1261-1264] at the rate of 10(15) m/s(2) when exposed to very intense IR laser pulses demonstrated that substantial fraction of atoms remained stable during the pulse. Here we show that the electronic structure of these stable "laser-dressed" atoms can be directly imaged by photoelectron spectroscopy. Our findings open the way to visualizing and controlling bound electron dynamics in strong laser fields and reexamining its role in various strong-field processes, including microscopic description of high order Kerr nonlinearities and their role in laser filamentation [Béjot et al. (2010) Phys Rev Lett 104:103903].

Complementation studies with the novel "Bungowannah" virus provide new insights in the compatibility of pestivirus proteins.

In recent years several atypical pestiviruses have been described. Bungowannah virus is the most divergent virus in this group. Therefore, heterologous complementation was used to clarify the phylogenetic relationship and to analyze the exchangeability of genome regions encoding structural proteins. Using a BVDV type 1 backbone, chimeric constructs with substituted envelope proteins E(rns), E1 and E2, were investigated. While all constructs replicated autonomously, infectious high titer chimeric virus could only be observed after exchanging the complete E1-E2 encoding region. The complementation of E1 and E2 alone resulted only in replicons. Complementation of BVDV-E(rns) was only efficient if Bungowannah virus-E(rns) was expressed from a bicistronic construct. Our data provide new insights in the compatibility of pestivirus proteins and demonstrate that heterologous complementation could be useful to characterize new pestiviruses.