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High-intensity, short-pulse lasers are crucial for generating energetic electrons that produce high-energy-density (HED) states in matter, offering potential applications in igniting dense fusion fuels for fast ignition laser fusion. High-density targets heated by these electrons exhibit spatially non-uniform and highly transient conditions, which have been challenging to characterize due to limitations in diagnostics that provide simultaneous high spatial and temporal resolution. Here, we employ an X-ray Free Electron Laser (XFEL) to achieve spatiotemporally resolved measurements at sub-micron and femtosecond scales on a solid-density copper foil heated by laser-driven fast electrons. Our X-ray transmission imaging reveals the formation of a solid-density hot plasma localized to the laser spot size, surrounded by Fermi degenerate, warm dense matter within a picosecond, and the energy relaxation occurring within the hot plasma over tens of picoseconds. These results validate 2D particle-in-cell simulations incorporating atomic processes and provide insights into the energy transfer mechanisms beyond current simulation capabilities. This work significantly advances our understanding of rapid fast electron heating and energy relaxation in solid-density matter, serving as a key stepping stone towards efficient high-density plasma heating and furthering the fields of HED science and inertial fusion energy research using intense, short-pulse lasers. Intense, short-pulse laser irradiation generates energetic electrons that heat targets to extreme conditions relevant to laser fusion. Here, authors used an X-ray Free Electron Laser to perform spatiotemporal measurements in solid-density copper foil with sub-micron and femtosecond resolutions.

Neutrons are powerful tools for investigating the structure and properties of materials used in science and technology. Recently, laser-driven neutron sources (LDNS) have attracted the attention of different communities, from science to industry, in a variety of applications, including radiography, spectroscopy, security, and medicine. However, the laser-driven ion acceleration mechanism for neutron generation and for establishing the scaling law on the neutron yield is essential to improve the feasibility of LDNS. In this paper, we report the mechanism that accelerates ions with spectra suitable for neutron generation. We show that the neutron yield increases with the fourth power of the laser intensity, resulting in the neutron generation of3×1011in4πat a maximum, with1.1×1019Wcm−2, 900 J, 1.5 ps lasers. By installing a “hand-size” moderator, which is specially designed for the LDNS, it is demonstrated that the efficient generation of epithermal (0.1–100 eV) neutrons enables the single-shot analysis of composite materials by neutron resonance transmission analysis (NRTA). We achieve the energy resolution of 2.3% for 5.19-eV neutrons 1.8 m downstream of the LDNS. This leads to the analysis of elements and isotopes within sub-μstimes and allows for high-speed nondestructive inspection.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9 ), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest =5.8 × 10-10 ), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest =1.9 × 10-9 ), TRANK1 (Pbest =2.1 × 10-9 ) and ODZ4 (Pbest =3.3 × 10-9 ). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest ~10-29 , R2 ~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest ~10-13 , R2 ~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

Increasing the laser energy absorption into energetic particle beams represents a longstanding quest in intense laser-plasma physics. During the interaction with matter, part of the laser energy is converted into relativistic electron beams, which are the origin of secondary sources of energetic ions, γ-rays and neutrons. Here we experimentally demonstrate that using multiple coherent laser beamlets spatially and temporally overlapped, thus producing an interference pattern in the laser focus, significantly improves the laser energy conversion efficiency into hot electrons, compared to one beam with the same energy and nominal intensity as the four beamlets combined. Two-dimensional particle-in-cell simulations support the experimental results, suggesting that beamlet interference pattern induces a periodical shaping of the critical density, ultimately playing a key-role in enhancing the laser-to-electron energy conversion efficiency. This method is rather insensitive to laser pulse contrast and duration, making this approach robust and suitable to many existing facilities. Enhanced coupling of laser energy to the target particles is a fundamental issue in laser-plasma interactions. Here the authors demonstrate increased photon absorption leading into higher laser to electron and proton energy transfer through the interference of multiple coherent beamlets.

Using one of the world most powerful laser facility, we demonstrate for the first time that high-contrast multi-picosecond pulses are advantageous for proton acceleration. By extending the pulse duration from 1.5 to 6 ps with fixed laser intensity of 10 18  W cm −2 , the maximum proton energy is improved more than twice (from 13 to 33 MeV). At the same time, laser-energy conversion efficiency into the MeV protons is enhanced with an order of magnitude, achieving 5% for protons above 6 MeV with the 6 ps pulse duration. The proton energies observed are discussed using a plasma expansion model newly developed that takes the electron temperature evolution beyond the ponderomotive energy in the over picoseconds interaction into account. The present results are quite encouraging for realizing ion-driven fast ignition and novel ion beamlines.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P =9.3 × 10 −9 , 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P =0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

High energy density physics is the field of physics dedicated to the study of matter and plasmas in extreme conditions of temperature, densities and pressures. It encompasses multiple disciplines such as material science, planetary science, laboratory and astrophysical plasma science. For the latter, high energy density states can be accompanied by extreme radiation environments and super-strong magnetic fields. The creation of high energy density states in the laboratory consists in concentrating/depositing large amounts of energy in a reduced mass, typically solid material sample or dense plasma, over a time shorter than the typical timescales of heat conduction and hydrodynamic expansion. Laser-generated, high current–density ion beams constitute an important tool for the creation of high energy density states in the laboratory. Focusing plasma devices, such as cone-targets are necessary in order to focus and direct these intense beams towards the heating sample or dense plasma, while protecting the proton generation foil from the harsh environments typical of an integrated high-power laser experiment. A full understanding of the ion beam dynamics in focusing devices is therefore necessary in order to properly design and interpret the numerous experiments in the field. In this work, we report a detailed investigation of large-scale, kilojoule-class laser-generated ion beam dynamics in focusing devices and we demonstrate that high-brilliance ion beams compress magnetic fields to amplitudes exceeding tens of kilo-Tesla, which in turn play a dominant role in the focusing process, resulting either in a worsening or enhancement of focusing capabilities depending on the target geometry.

Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2 , P =1.14 × 10 −12 , odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1 , P =4.96 × 10 −10 , OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT , P =7.94 × 10 −10 , OR=0.87; rs10883765 at an intron of ARL3 , P =3.06 × 10 −9 , OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case–control status in the Chinese population (Nagelkerke R 2 : 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

A pulsating heat pipe (PHP) is a promising two-phase passive thermal device that consists of a capillary tube meandering between an evaporator and a condenser. Heat is transferred from the evaporator to the condenser by the self-excited oscillation of vapor and liquid. The complete knowledge of the heat transport mechanisms, particularly at the operating limit of PHPs, is far from satisfactory. In PHP, the phase-change acts as a driving force of the self-excited oscillation of the fluid. In this context, the condensation highly affects the performance of PHPs, while few studies have investigated the effect of the sink temperature or the cooling methods. In this study, a single metallic loop is tested to understand the local phenomena focusing on the impact of cooling methods of the condenser section: natural convection and forced air convection. Regardless of the cooling methods, the PHP showed the intermittent and unstable oscillation at low power input just after the start-up, and then continued to operate stably until the heater turned off after the evaporator temperature exceeds 140 °C. The resistance of natural convection cooling is more than 1 K/W lower than that of forced convection cooling, for the same heat input conditions. However, the resistance of both cooling methods at the same evaporator temperature shows a good agreement. The resistance is inversely proportional to the evaporator temperature as well as the heat input.

It has long been recognized that generalized deficits in cognitive ability represent a core component of schizophrenia (SCZ), evident before full illness onset and independent of medication. The possibility of genetic overlap between risk for SCZ and cognitive phenotypes has been suggested by the presence of cognitive deficits in first-degree relatives of patients with SCZ; however, until recently, molecular genetic approaches to test this overlap have been lacking. Within the last few years, large-scale genome-wide association studies (GWAS) of SCZ have demonstrated that a substantial proportion of the heritability of the disorder is explained by a polygenic component consisting of many common single-nucleotide polymorphisms (SNPs) of extremely small effect. Similar results have been reported in GWAS of general cognitive ability. The primary aim of the present study is to provide the first molecular genetic test of the classic endophenotype hypothesis, which states that alleles associated with reduced cognitive ability should also serve to increase risk for SCZ. We tested the endophenotype hypothesis by applying polygenic SNP scores derived from a large-scale cognitive GWAS meta-analysis (~5000 individuals from nine nonclinical cohorts comprising the Cognitive Genomics consorTium (COGENT)) to four SCZ case-control cohorts. As predicted, cases had significantly lower cognitive polygenic scores compared to controls. In parallel, polygenic risk scores for SCZ were associated with lower general cognitive ability. In addition, using our large cognitive meta-analytic data set, we identified nominally significant cognitive associations for several SNPs that have previously been robustly associated with SCZ susceptibility. Results provide molecular confirmation of the genetic overlap between SCZ and general cognitive ability, and may provide additional insight into pathophysiology of the disorder.