Machine learning accelerated random structure searching: Application to yttrium superhydrides.

The search for new superhydrides, promising materials for both hydrogen storage and high temperature superconductivity, made great progress, thanks to atomistic simulations and Crystal Structure Prediction (CSP) algorithms. When they are combined with Density Functional Theory (DFT), these methods are highly reliable and often match a great part of the experimental results. However, systems of increasing complexity (number of atoms and chemical species) become rapidly challenging as the number of minima to explore grows exponentially with the number of degrees of freedom in the simulation cell. An efficient sampling strategy preserving a sustainable computational cost then remains to be found. We propose such a strategy based on an active-learning process where machine learning potentials and DFT simulations are jointly used, opening the way to the discovery of complex structures. As a proof of concept, this method is applied to the exploration of tin crystal structures under various pressures. We showed that the α phase, not included in the learning process, is correctly retrieved, despite its singular nature of bonding. Moreover, all the expected phases are correctly predicted under pressure (20 and 100 GPa), suggesting the high transferability of our approach. The method has then been applied to the search of yttrium superhydrides (YHx) crystal structures under pressure. The YH6 structure of space group Im-3m is successfully retrieved. However, the exploration of more complex systems leads to the appearance of a large number of structures. The selection of the relevant ones to be included in the active learning process is performed through the analysis of atomic environments and the clustering algorithm. Finally, a metric involving a distance based on x-ray spectra is introduced, which guides the structural search toward experimentally relevant structures. The global process (active-learning and new selection methods) is finally considered to explore more complex and unknown YHx phases, unreachable by former CSP algorithms. New complex phases are found, demonstrating the ability of our approach to push back the exponential wall of complexity related to CSP.

Experimental study of modulation waveforms for entraining the spikes emitted by a semiconductor laser with optical feedback.

The entrainment phenomenon, by which an oscillator adjusts its natural rhythm to an external periodic signal, has been observed in many natural systems. Recently, attention has focused on which are the optimal conditions for achieving entrainment. Here we use a semiconductor laser with optical feedback, operating in the low-frequency fluctuations (LFFs) regime, as a testbed for a controlled entrainment experiment. In the LFF regime the laser intensity displays abrupt spikes, which can be entrained to a weak periodic signal that directly modulates the laser pump current. We compare the performance of three modulation waveforms for producing 1:1 locking (one spike is emitted in each modulation cycle), as well as higher order locking regimes. We characterize the parameter regions where high-quality locking occurs, and those where the laser emits spikes which are not entrained to the external signal. The role of the modulation amplitude and frequency, and the role of the dc value of the laser pump current (that controls the natural spike frequency) in the entrainment quality are discussed.

State space reconstruction of spatially extended systems and of time delayed systems from the time series of a scalar variable.

The space-time representation of high-dimensional dynamical systems that have a well defined characteristic time scale has proven to be very useful to deepen the understanding of such systems and to uncover hidden features in their output signals. By using the space-time representation many analogies between one-dimensional spatially extended systems (1D SESs) and time delayed systems (TDSs) have been found, including similar pattern formation and propagation of localized structures. An open question is whether such analogies are limited to the space-time representation, or it is also possible to recover similar evolutions in a low-dimensional pseudo-space. To address this issue, we analyze a 1D SES (a bistable reaction-diffusion system), a scalar TDS (a bistable system with delayed feedback), and a non-scalar TDS (a model of two delay-coupled lasers). In these three examples, we show that we can reconstruct the dynamics in a three-dimensional phase space, where the evolution is governed by the same polynomial potential. We also discuss the limitations of the analogy between 1D SESs and TDSs.

Differentiating resting brain states using ordinal symbolic analysis.

Symbolic methods of analysis are valuable tools for investigating complex time-dependent signals. In particular, the ordinal method defines sequences of symbols according to the ordering in which values appear in a time series. This method has been shown to yield useful information, even when applied to signals with large noise contamination. Here, we use ordinal analysis to investigate the transition between eyes closed (EC) and eyes open (EO) resting states. We analyze two electroencephalography datasets (with 71 and 109 healthy subjects) with different recording conditions (sampling rates and the number of electrodes in the scalp). Using as diagnostic tools the permutation entropy, the entropy computed from symbolic transition probabilities, and an asymmetry coefficient (that measures the asymmetry of the likelihood of the transitions between symbols), we show that the ordinal analysis applied to the raw data distinguishes the two brain states. In both datasets, we find that, during the EC-EO transition, the EO state is characterized by higher entropies and lower asymmetry coefficient, as compared to the EC state. Our results thus show that these diagnostic tools have the potential for detecting and characterizing changes in time-evolving brain states.

Experimental characterization of the transition to coherence collapse in a semiconductor laser with optical feedback.

Semiconductor lasers with time-delayed optical feedback display a wide range of dynamical regimes, which have found various practical applications. They also provide excellent testbeds for data analysis tools for characterizing complex signals. Recently, several of us have analyzed experimental intensity time-traces and quantitatively identified the onset of different dynamical regimes, as the laser current increases. Specifically, we identified the onset of low-frequency fluctuations (LFFs), where the laser intensity displays abrupt dropouts, and the onset of coherence collapse (CC), where the intensity fluctuations are highly irregular. Here we map these regimes when both, the laser current and the feedback strength vary. We show that the shape of the distribution of intensity fluctuations (characterized by the standard deviation, the skewness, and the kurtosis) allows to distinguish among noise, LFFs and CC, and to quantitatively determine (in spite of the gradual nature of the transitions) the boundaries of the three regimes. Ordinal analysis of the inter-dropout time intervals consistently identifies the three regimes occurring in the same parameter regions as the analysis of the intensity distribution. Simulations of the well-known time-delayed Lang-Kobayashi model are in good qualitative agreement with the observations.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Unveiling Temporal Correlations Characteristic of a Phase Transition in the Output Intensity of a Fiber Laser.

We use advanced statistical tools of time-series analysis to characterize the dynamical complexity of the transition to optical wave turbulence in a fiber laser. Ordinal analysis and the horizontal visibility graph applied to the experimentally measured laser output intensity reveal the presence of temporal correlations during the transition from the laminar to the turbulent lasing regimes. Both methods unveil coherent structures with well-defined time scales and strong correlations both, in the timing of the laser pulses and in their peak intensities. Our approach is generic and may be used in other complex systems that undergo similar transitions involving the generation of extreme fluctuations.

Effects of periodic forcing on the temporally correlated spikes of a semiconductor laser with feedback.

Optical excitable devices that mimic neuronal behavior can be building-blocks of novel, brain-inspired information processing systems. A relevant issue is to understand how such systems represent, via correlated spikes, the information of a weak external input. Semiconductor lasers with optical feedback operating in the low frequency fluctuations regime have been shown to display optical spikes with intrinsic temporal correlations similar to those of biological neurons. Here we investigate how the spiking laser output represents a weak periodic input that is implemented via direct modulation of the laser pump current. We focus on understanding the influence of the modulation frequency. Experimental sequences of inter-spike-intervals (ISIs) are recorded and analyzed by using the ordinal symbolic methodology that identifies and characterizes serial correlations in datasets. The change in the statistics of the various symbols with the modulation frequency is empirically shown to be related to specific changes in the ISI distribution, which arise due to different phase-locking regimes. A good qualitative agreement is also found between simulations of the Lang and Kobayashi model and observations. This methodology is an efficient way to detect subtle changes in noisy correlated ISI sequences and may be applied to investigate other optical excitable devices.

Early-life house dust mite allergens, childhood mite sensitization, and respiratory outcomes.

BACKGROUND: Exposure to indoor allergens during early life may play a role in the development of the immune system and inception of asthma. OBJECTIVE: To describe the house dust mite (HDM) allergen concentrations in bedroom dust during early life and to evaluate its associations with HDM sensitization, wheezing, and asthma, from birth to school age, in 5 geographically spread European birth cohorts. METHODS: We included 4334 children from INMA-Menorca (Spain), BAMSE (Sweden), LISAplus and MAS (Germany), and PIAMA-NHS (the Netherlands). Dust samples were collected from bedrooms during early life and analyzed for Dermatophagoides pteronyssinus (Der p1) and Dermatophagoides farinae (Der f1). HDM concentrations were divided into four categories. Sensitization was determined by specific IgE. Wheezing and asthma information up to 8/10 years was collected through questionnaires. We performed mixed-effects logistic regression models and expressed associations as odds ratios with 95% confidence intervals. RESULTS: House dust mite concentrations varied across cohorts. Mean allergen concentrations were highest in INMA-Menorca (geometric mean (GM) Der p1 = 3.3 µg/g) and LISAplus (GM Der f1 = 2.1 µg/g) and lowest in BAMSE (GM Der p1 = 0.1 µg/g, Der f1 = 0.3 µg/g). Moderate and high HDM concentrations were significantly (P-values < 0.05) associated with 50-90% higher prevalence of HDM sensitization. No significant associations were observed with respiratory outcomes. CONCLUSION: Our study based on geographically spread regions, a large sample size, and a wide range of allergen concentration shows that HDM allergen concentrations vary across regions and that exposure during early life plays a role in the development of allergic sensitization but not in the development of respiratory outcomes.

Experimental and numerical study of the symbolic dynamics of a modulated external-cavity semiconductor laser.

We study the symbolic dynamics of a stochastic excitable optical system with periodic forcing. Specifically, we consider a directly modulated semiconductor laser with optical feedback in the low frequency fluctuations (LFF) regime. We use a method of symbolic time-series analysis that allows us to uncover serial correlations in the sequence of intensity dropouts. By transforming the sequence of inter-dropout intervals into a sequence of symbolic patterns and analyzing the statistics of the patterns, we unveil correlations among several consecutive dropouts and we identify clear changes in the dynamics as the modulation amplitude increases. To confirm the robustness of the observations, the experiments were performed using two lasers under different feedback conditions. Simulations of the Lang-Kobayashi (LK) model, including spontaneous emission noise, are found to be in good agreement with the observations, providing an interpretation of the correlations present in the dropout sequence as due to the interplay of the underlying attractor topology, the external forcing, and the noise that sustains the dropout events.

Impact of a non-attentively perceived odour on subsequent food choices.

Current research in psychology suggests that unconscious processes influence a significant proportion of choices and decisions. To study the impact of a non-attentively perceived odour on food choices, we used a priming paradigm. We had previously shown that non-attentively perceived fruity odours could impact food choice intentions (on a menu card), guiding participants toward items containing more fruit and/or vegetables. The present study was designed to extend these findings, in a real-life consumption setting. One hundred and fifteen participants took part in this study, and were assigned randomly to either a control or a scented condition. On arrival in the laboratory, they were seated in a waiting room. For the scented condition, they were unobtrusively exposed to a pear odour, while under the control condition the waiting room was non-odorised. Following this waiting period, all participants moved into a non-odorised test room where they were asked to choose, from dishes served buffet-style, the starter, main course and dessert that they would actually eat for lunch. The results showed that participants subjected to the scented condition chose to consume the 'fruity' dessert (compote) more frequently than those who had waited under the control condition, who chose more frequently the dessert without fruit (brownie). In line with the findings of our previous study, these results confirm the idea of priming effects 'specific to the food cue'. To conclude, a non-attentively perceived fruity odour was shown to influence actual food choices, guiding individuals towards more fruity desserts. The involvement of implicit processes in food choices should be taken into account in guidelines and strategies designed to promote healthy eating.

Multidimensional subwavelength position sensing using a semiconductor laser with optical feedback.

We demonstrate experimentally how to harness quasi-periodic dynamics in a semiconductor laser with dual optical feedback for measuring subwavelength changes in each arm of the cavity simultaneously. We exploit the multifrequency spectrum of quasi-periodic dynamics and show that independent frequency shifts are mapped uniquely to two-dimensional displacements of the arms in the external cavity. Considering a laser diode operating at telecommunication wavelength λ≈1550 nm, we achieve an average nanoscale resolution of approximately 9.8 nm (~λ/160).

Endotoxin, extracellular polysaccharides, and ß(1-3)-glucan concentrations in dust and their determinants in four European birth cohorts: results from the HITEA project.

UNLABELLED: Early-life exposure to microbial agents may play a protective role in asthma and allergies development. Geographical differences in the prevalence of these diseases exist, but the differences in early-life indoor microbial agent levels and their determinants have been hardly studied. We aimed to describe the early-life levels of endotoxin, extracellular polysaccharides (EPS), and ß(1-3)-glucans in living room dust of four geographically spread European birth cohorts (LISA in Germany, PIAMA in the Netherlands, INMA in Spain, and LUKAS2 in Finland) and to assess their determinants. A total of 1572 dust samples from living rooms of participants were analyzed for endotoxin, Penicillium/Aspergillus EPS, and ß(1-3)-glucans. Information on potential determinants was obtained through questionnaires. Concentrations of endotoxin, EPS, and ß(1-3)-glucans were different across cohorts. Concentrations of endotoxin and EPS were respectively lower and higher in INMA than in other cohorts, while glucans were higher in LUKAS2. Season of sampling, dog ownership, dampness, and the number of people living at home were significantly associated with concentrations of at least one microbial agent, with heterogeneity of effect estimates of the determinants across cohorts. In conclusion, both early-life microbial exposure levels and exposure determinants differ across cohorts derived from diverse European countries. PRACTICAL IMPLICATIONS: This study adds evidence of variability in the levels of indoor endotoxin, extracellular polysaccharide, and ß(1-3)-glucans across four geographically spread European regions. Furthermore, we observed heterogeneity across regions in the effect of exposure determinants. We hypothesize that the variations observed in our study may play a role in the differences in asthma and allergies prevalences across countries.

Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia.

Recent advances in treatment for childhood acute lymphoblastic leukaemia (ALL) have significantly increased outcome. High-dose methotrexate (MTX) is the most commonly used regimen during the consolidation period, but the optimal dose remains to be defined. We investigated the usefulness of the MTHFR genotype to increase the MTX dosage in the consolidation phase in 141 childhood ALL patients enrolled in the ALL/SHOP-2005 protocol. We also investigated the pharmacogenetic role of polymorphisms in genes involved in MTX metabolism on therapy-related toxicity and survival. Patients with a favourable MTHFR genotype (normal enzymatic activity) treated with MTX doses of 5 g m⁻² had a significantly lower risk of suffering an event than patients with an unfavourable MTHFR genotype (reduced enzymatic activity) that were treated with the classical MTX dose of 3 g m⁻² (P=0.012). Our results indicate that analysis of the MTHFR genotype is a useful tool to optimise MTX therapy in childhood patients with ALL.

No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients.

BACKGROUND: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. PATIENTS AND METHODS: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. RESULTS: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). CONCLUSIONS: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.

WT1 mutations may be a cause of severe renal failure due to nephroblastomatosis in Wilms' tumor patients.

Wilms' tumor suppressor gene (WT1) encodes a transcription factor required for normal development of the genitourinary system. Germline WT1 mutations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms' tumor. Here we report a 4-year-old male patient who presented with bilateral cryptorchidism, Wilms' tumor, nephroblastomatosis and renal failure without nephrotic proteinuria. Sequence analysis of the WT1 gene demonstrated a constitutional heterozygous nonsense mutation in exon 7, which leads to a truncation of the WT1 protein at the zinc-finger 1. In the DNA of the tumor, we observed the same mutation in homo/hemizygosity. Given the requirement of WT1 for normal development, the WT1 mutation is likely to be responsible for the nephroblastomatosis and, in consequence, for the severe renal failure observed in our patient. This finding extends the spectrum of kidney diseases related to WT1 mutations and points to the need to screen for this gene in children with genitourinary abnormalities and Wilms' tumor because of the associated risk of nephroblastomatosis and renal failure in those carrying WT1 mutations.

Dual-lag synchronization between coupled chaotic lasers due to path-delay interference.

We study experimentally the synchronization dynamics of two semiconductor lasers coupled unidirectionally via two different delayed paths. The emitter laser operates in a chaotic regime characterized by low-frequency fluctuations due to optical feedback and induces a synchronized dynamical activity in the receiver laser, which operates in the continuous-wave regime when uncoupled. Different delays in the two coupling paths lead to the coexistence of two time lags in the synchronized dynamics of the oscillators. This dual-lag synchronization degrades the average synchronization quality of the system of coupled lasers and hinders the transmission of information between them. Numerical simulation results agree with the experimental observations, and allow us to explore this phenomenon in a wide parameter range, and quantify the degree of signal transmission degradation caused by this chaotic path-delay interference.

Rare-earth surface alloying: a new phase for GdAu2.

Surface alloying is a powerful way of varying physical and chemical properties of metals, for a number of applications from catalysis to nuclear and green technologies. Surfaces offer many degrees of freedom, giving rise to new phases that do not have a bulk counterpart. However, the atomic characterization of distinct surface compounds is a major task, which demands powerful experimental and theoretical tools. Here we illustrate the process for the case of a GdAu2 surface phase of extraordinary crystallinity. The combined use of surface-sensitive techniques and state-of-the-art ab initio calculations disentangles its atomic and electronic properties. In particular, the stacking of the surface layers allows for gadolinium's natural ferromagnetic state, at variance with the bulk phase, where frustration leads to antiferromagnetic interlayer coupling.