Prediction of the superimposed laser shot number for copper using a deep convolutional neural network.

Image-based deep learning (IBDL) is an advanced technique for predicting the surface irradiation conditions of laser surface processing technology. In pulsed-laser surface processing techniques, the number of superimposed laser shots is one of the fundamental and essential parameters that should be optimized for each material. Our primary research aims to build an adequate dataset using laser-irradiated surface images and to successfully predict the number of superimposed shots using the pre-trained deep convolutional neural network (CNN) models. First, the laser shot experiments were performed on copper targets using a nanosecond YAG laser with a wavelength of 532 nm. Then, the training data were obtained with the different superimposed shots of 1 to 1024 in powers of 2. After that, we used several pre-trained deep CNN models to predict the number of superimposed laser shots. Based on the dataset with 1936 images, VGG16 shows a high validation accuracy, higher sensitivity, and more than 99% precision than other deep CNN models. Utilizing the VGG16 model with high sensitivity could positively impact the industries' time, efficiency, and overall production.

Erratum: Using Diffuse Scattering to Observe X-Ray-Driven Nonthermal Melting [Phys. Rev. Lett. 126, 015703 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.126.015703.

Liquid Structure of Tantalum under Internal Negative Pressure.

In situ femtosecond x-ray diffraction measurements and ab initio molecular dynamics simulations were performed to study the liquid structure of tantalum shock released from several hundred gigapascals (GPa) on the nanosecond timescale. The results show that the internal negative pressure applied to the liquid tantalum reached -5.6 (0.8) GPa, suggesting the existence of a liquid-gas mixing state due to cavitation. This is the first direct evidence to prove the classical nucleation theory which predicts that liquids with high surface tension can support GPa regime tensile stress.

Using Diffuse Scattering to Observe X-Ray-Driven Nonthermal Melting.

We present results from the SPring-8 Angstrom Compact free electron LAser facility, where we used a high intensity (∼10^{20} W/cm^{2}) x-ray pump x-ray probe scheme to observe changes in the ionic structure of silicon induced by x-ray heating of the electrons. By avoiding Laue spots in the scattering signal from a single crystalline sample, we observe a rapid rise in diffuse scattering and a transition to a disordered, liquidlike state with a structure significantly different from liquid silicon. The disordering occurs within 100 fs of irradiation, a timescale that agrees well with first principles simulations, and is faster than that predicted by purely inertial behavior, suggesting that both the phase change and disordered state reached are dominated by Coulomb forces. This method is capable of observing liquid scattering without masking signal from the ambient solid, allowing the liquid structure to be measured throughout and beyond the phase change.

Morphological development of Pleurochrysis carterae coccoliths examined by cryo-electron tomography.

Coccolithophores are single-celled marine algae that produce calcified scales called coccoliths. Each scale is composed of anvil-shaped single crystals of calcite that are mechanically interlocked, constituting a remarkable example of the multi-level construction of mineralized structures. Coccolith formation starts with the nucleation of rhombohedral crystals on an organic substrate called base plate. The crystals then grow preferentially along specific directions to generate the mature structure, which is then transported to the outside of the cells. Here, we extracted forming coccoliths from Pleurochrysis carterae cells and used cryo-electron tomography to characterize, in their native, hydrated state, the three-dimensional morphology and arrangement of the crystals. Comparing the crystal morphology across three different stages of coccolith formation, we show that competition for space between adjacent crystals contributes significantly to regulation of morphology by constraining growth in certain directions. We further demonstrate that crystals within a coccolith ring develop at different rates and that each crystalline unit rests directly in contact with the base plate and overgrow the rim of the organic substrate during development.

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

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.

High-resolution copy number variation analysis of schizophrenia in Japan.

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.

Coherent X-ray beam metrology using 2D high-resolution Fresnel-diffraction analysis.

Direct metrology of coherent short-wavelength beamlines is important for obtaining operational beam characteristics at the experimental site. However, since beam-time limitation imposes fast metrology procedures, a multi-parametric metrology from as low as a single shot is desirable. Here a two-dimensional (2D) procedure based on high-resolution Fresnel diffraction analysis is discussed and applied, which allowed an efficient and detailed beamline characterization at the SACLA XFEL. So far, the potential of Fresnel diffraction for beamline metrology has not been fully exploited because its high-frequency fringes could be only partly resolved with ordinary pixel-limited detectors. Using the high-spatial-frequency imaging capability of an irradiated LiF crystal, 2D information of the coherence degree, beam divergence and beam quality factor M2 were retrieved from simple diffraction patterns. The developed beam metrology was validated with a laboratory reference laser, and then successfully applied at a beamline facility, in agreement with the source specifications.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Effect of Adjunctive Aripiprazole on Sexual Dysfunction in Schizophrenia: A Preliminary Open-Label Study.

Introduction: Although adjunctive aripiprazole improves hyperprolactinemia, sufficient evidence for its effects on sexual dysfunction has not been obtained. We assessed the usefulness of adjunctive aripiprazole for schizophrenia with sexual dysfunction. Methods: 22 Japanese schizophrenia patients with antipsychotic-induced hyperprolactinemia and sexual dysfunction were enrolled, and 19 of them completed the study. Aripiprazole was administrated in a flexible titration schedule to participants according to the judgment of each doctor, and patients were followed for 24 weeks. Serum prolactin, Clinical Global Impression Scales-Severity (CGI-S), and Nagoya Sexual Function Questionnaire (NSFQ) were measured at baseline and at 4, 8, 12, and 24 weeks. Results: Prolactin at week 4 and later was significantly lower than that at baseline. Compared to baseline, we observed a significant improvement in total sexual dysfunction as measured by NSFQ at week 8 and later. In males, erectile dysfunction was significantly reduced at week 24. In females, menstrual irregularity and galactorrhea were significantly reduced at week 24. CGI-S did not significantly change. Discussion: Although the small sample size is a limitation in this study, adjunctive aripiprazole may be useful treatment for sexual dysfunction including hyperprolactinemia in schizophrenia.

Genome-wide association study identifies a potent locus associated with human opioid sensitivity.

Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity. By conducting a multistage genome-wide association study (GWAS) in healthy subjects, we found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate single-nucleotide polymorphism (SNP), rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. These results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence.

P-ρ-T measurements of H2O up to 260 GPa under laser-driven shock loading.

Pressure, density, and temperature data for H2O were obtained up to 260 GPa by using laser-driven shock compression technique. The shock compression technique combined with the diamond anvil cell was used to assess the equation of state models for the P-ρ-T conditions for both the principal Hugoniot and the off-Hugoniot states. The contrast between the models allowed for a clear assessment of the equation of state models. Our P-ρ-T data totally agree with those of the model based on quantum molecular dynamics calculations. These facts indicate that this model is adopted as the standard for modeling interior structures of Neptune, Uranus, and exoplanets in the liquid phase in the multi-Mbar range.

Iron plays a key role in the cytodifferentiation of human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: The periodontal ligament (PDL) is vital to maintaining the homeostasis of the tooth and periodontal tissue. The influence of iron levels on the cytodifferentiation of PDL cells has not been studied, despite evidence that iron overload or deficiency can have adverse effects on alveolar bone density. The purpose of this study was to examine the effects of altered iron levels on cytodifferentiation in human PDL cells. MATERIAL AND METHODS: Human PDL cells were incubated with culture media supplemented with 10-50 µm ammonium ferric citrate or 5 µm deferoxamine (an iron chelator) during differentiation. Intracellular iron status was assessed by measuring changes in the expression of ferritin RNA and protein. PDL cell differentiation and function were evaluated by measuring osteoblast differentiation gene markers and the capacity of cultures to form mineralized nodules. RESULTS: Iron accumulation resulted in upregulation of light and heavy chain ferritin proteins. Concurrently, osteoblast differentiation gene markers and mineralized nodule formation were suppressed. Iron deficiency resulted in downregulation of light and heavy chain ferritin proteins, suppression of alkaline phosphatase activity and formation of mineralized nodules during PDL cell differentiation. CONCLUSION: We conclude that iron is critical for normal cell differentiation of human PDL cells.

Advanced spectroscopic investigation of colour centres in LiF crystals irradiated with monochromatic hard x-rays.

Nominally-pure lithium fluoride (LiF) crystals were irradiated with monochromatic hard x-rays of energy 5, 7, 9 and 12 keV at the METROLOGIE beamline of the SOLEIL synchrotron facility, in order to understand the role of the selected x-ray energy on their visible photoluminescence (PL) response, which is used for high spatial resolution 2D x-ray imaging detectors characterized by a wide dynamic range. At the energies of 7 and 12 keV the irradiations were performed at five different doses corresponding to five uniformly irradiated areas, while at 5 and 9 keV only two irradiations at two different doses were carried out. The doses were planned in a range between 4 and 1.4 × 103Gy (10.5 mJ cm-3to 3.7 J cm-3), depending on the x-ray energy. After irradiation at the energies of 7 and 12 keV, the spectrally-integrated visible PL intensity of the F2and F3+colour centres (CCs) generated in the LiF crystals, carefully measured by fluorescence microscopy under blue excitation, exhibits a linear dependence on the irradiation dose in the investigated dose range. This linear behaviour was confirmed by the optical absorption spectra of the irradiated spots, which shows a similar linear behaviour for both the F2and F3+CCs, as derived from their overlapping absorption band at around 450 nm. At the highest x-ray energy, the average concentrations of the radiation-induced F, F2and F3+CCs were also estimated. The volume distributions of F2defects in the crystals irradiated with 5 and 9 keV x-rays were reconstructed in 3D by measuring their PL signal using a confocal laser scanning microscope operating in fluorescence mode. On-going investigations are focusing on the results obtained through thisz-scanning technique to explore the potential impact of absorption effects at the excitation laser wavelength.

DPP6 as a candidate gene for neuroleptic-induced tardive dyskinesia.

We implemented a two-step approach to detect potential predictor gene variants for neuroleptic-induced tardive dyskinesia (TD) in schizophrenic subjects. First, we screened associations by using a genome-wide (Illumina HumanHapCNV370) SNP array in 61 Japanese schizophrenia patients with treatment-resistant TD and 61 Japanese schizophrenia patients without TD. Next, we performed a replication analysis in 36 treatment-resistant TD and 138 non-TD subjects. An association of an SNP in the DPP6 (dipeptidyl peptidase-like protein-6) gene, rs6977820, the most promising association identified by the screen, was significant in the replication sample (allelic P=0.008 in the replication sample, allelic P=4.6 × 10(-6), odds ratio 2.32 in the combined sample). The SNP is located in intron-1 of the DPP6 gene and the risk allele was associated with decreased DPP6 gene expression in the human postmortem prefrontal cortex. Chronic administration of haloperidol increased Dpp6 expression in mouse brains. DPP6 is an auxiliary subunit of Kv4 and regulates the properties of Kv4, which regulates the activity of dopaminergic neurons. The findings of this study indicate that an altered response of Kv4/DPP6 to long-term neuroleptic administration is involved in neuroleptic-induced TD.

Electrostatic properties of confluent Caco-2 cell layer correlates to their microvilli growth and determines underlying transcellular flow.

Recently, Rajapaksa et al. (2010) showed that the rate of uptake of potential vaccine delivery nanoparticles in the mucosal layer is a function of the electrostatic properties of the corresponding solvent. This fundamentally implies that the dominant driving forces that may be capitalized on for mucosal vaccine strategies are electrostatic in nature. We hypothesize that the driving force normal to the cell (in the direction from apical to basolateral across the cell) is of particular importance. In addition, it has been theoretically shown that the electrostatic properties of mucosal cells are directly related to their development of brush border. Here we correlate the development of brush border on a human mucosal epithelial model (Caco-2) cultured in DMEM on 3.0 µm pore sized polycarbonate membranes to their corresponding electrostatic properties characterized by measuring their normal zeta potential. Properties of normal streaming potential, hydraulic permeability, and brush border development (as determined by size and number) were monitored for 2, 6, and 16 days (after cells were confluent). Human endothelial cells (HECs), which lack brush border, were used as the control. Our results demonstrate that normal zeta potential of Caco-2 cells significantly changed from -5.7 ± 0.11 mV to -3.4 ± 0.11 mV for a period between 2 and 16 days, respectively. The zeta potential of the control cell line, HECs, stayed constant (statistically not different, P > 0.05) for the duration of the experiments. Our results show that the calculated increase in surface area of the Caco-2 cells with microvilli from 6 to 16 days was directly proportional to the corresponding measured zeta potential difference. These results imply that microvilli alter the electrostatic local environment around Caco-2 cells and, hence, enhance the normal electrostatic selective transport of solute across the mucosal barrier.

Comparison of quality of life and psychological distress in patients with tongue cancer undergoing a total/subtotal glossectomy or extended hemiglossectomy and free flap transfer: a prospective evaluation.

The aim of this study was to assess changes in the quality of life and psychological distress of patients with tongue cancer undergoing total/subtotal glossectomy (TG) or extended hemiglossectomy (HG) and free flap transfer. Differences between the two groups were compared using the Short Form 8-Item Health Survey (SF-8) and Hospital Anxiety and Depression Scale (HADS). Of the 43 patients with tongue cancer, 24 (56%) underwent TG and 19 (44%) underwent HG. The general health and social functioning scores in the SF-8 and depression in the HADS were significantly worse in the TG group than in the HG group at 12 months after surgery, indicating that patients in the TG group may experience social isolation and psychological distress, and have difficulty in employability even 12 months after surgery. In contrast, all items of the SF-8 in the HG group were nearly equal to those in the general population. Due to the extensive psychological impact on patients with tongue cancer who are planned for an extended resection, curative surgery with free flap transfer and multidisciplinary psychiatric support are essential to improve quality of life and manage psychological distress.

Amelogenin enhances the osteogenic differentiation of mesenchymal stem cells derived from bone marrow.

Amelogenins are the major constituent of developing extracellular enamel matrix proteins and are understood to have an exclusively epithelial origin. Recent studies have demonstrated that amelogenins can be detected in other tissues, including bone marrow mesenchymal stem cells (MSCs), but the role of amelogenins in MSCs remains unclear. The purpose of this study was to examine the effect of recombinant human full-length amelogenin (rh174) on the osteogenic differentiation of cultured human MSCs. MSCs isolated from human bone marrow were cultured in osteoblastic differentiation medium with 0, 10 or 100 ng/ml rh174. The mRNA levels of bone markers were examined by real-time PCR analysis. Alkaline phosphatase (ALP) activity and calcium concentration were determined. Mineralization was evaluated by alizarin red staining. The mRNA levels of ALP, type I collagen, osteopontin and bone sialoprotein in the MSCs treated with rh174 became significantly higher than those in non-treated controls. Treatment of MSCs with rh174 also enhanced ALP activity and calcium concentration, resulting in enhanced mineralization, as denoted by high intensity of alizarin red staining. In conclusion, the present study showed that rh174 enhances the mineralization accompanied by the upregulation of bone markers in human bone marrow MSCs during osteogenic differentiation, suggesting a certain role of amelogenin in the modulation of osteogenic differentiation of MSCs.

Development of an experimental platform for the investigation of laser-plasma interaction in conditions relevant to shock ignition regime.

The shock ignition (SI) approach to inertial confinement fusion is a promising scheme for achieving energy production by nuclear fusion. SI relies on using a high intensity laser pulse (≈1016 W/cm2, with a duration of several hundred ps) at the end of the fuel compression stage. However, during laser-plasma interaction (LPI), several parametric instabilities, such as stimulated Raman scattering and two plasmon decay, nonlinearly generate hot electrons (HEs). The whole behavior of HE under SI conditions, including their generation, transport, and final absorption, is still unclear and needs further experimental investigation. This paper focuses on the development of an experimental platform for SI-related experiments, which simultaneously makes use of multiple diagnostics to characterize LPI and HE generation, transport, and energy deposition. Such diagnostics include optical spectrometers, streaked optical shadowgraph, an x-ray pinhole camera, a two-dimensional x-ray imager, a Cu Kα line spectrometer, two hot-electron spectrometers, a hard x-ray (bremsstrahlung) detector, and a streaked optical pyrometer. Diagnostics successfully operated simultaneously in single-shot mode, revealing the features of HEs under SI-relevant conditions.

Direct observations of pure electron outflow in magnetic reconnection.

Magnetic reconnection is a universal process in space, astrophysical, and laboratory plasmas. It alters magnetic field topology and results in energy release to the plasma. Here we report the experimental results of a pure electron outflow in magnetic reconnection, which is not accompanied with ion flows. By controlling an applied magnetic field in a laser produced plasma, we have constructed an experiment that magnetizes the electrons but not the ions. This allows us to isolate the electron dynamics from the ions. Collective Thomson scattering measurements reveal the electron Alfvénic outflow without ion outflow. The resultant plasmoid and whistler waves are observed with the magnetic induction probe measurements. We observe the unique features of electron-scale magnetic reconnection simultaneously in laser produced plasmas, including global structures, local plasma parameters, magnetic field, and waves.