Author: "Ozaki, N." / Database: OpenAIRE - Searchworks@Jio Institute Digital Library Search Results

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49 results on '"Ozaki, N."'

1. Dust impact and attitude analysis for JAXA’s probe on the Comet Interceptor mission

Author: Machuca, P., Ozaki, N., Sa´nchez, J. P., and Felicetti, Leonard
Subjects: Atmospheric Science, Geophysics, System requirements, Space and Planetary Science, Monte Carlo analysis, Aerospace Engineering, General Earth and Planetary Sciences, Astronomy and Astrophysics, Long-period comet
Abstract: Comet Interceptor (Comet-I), to be launched in 2029 as a piggyback to ESA’s ARIEL mission, is aimed to perform the first fly-by of a pristine long-period comet. The mission will be composed of a main spacecraft, SC A (ESA), and two small probes to be released prior to the fly-by, SC B1 (JAXA) and SC B2 (ESA). This work analyzes the attitude performance of JAXA’s 24U-sized spacecraft through the dust environment of a yet-to-be-discovered target comet. Main challenges to the mission are associated to the high levels of uncertainty and extremity of fly-by conditions: highly-active dust environment, uncertain fly-by altitude (750 ± 250 km (1σ), as of 2021), and large and unknown relative fly-by speeds (15–70 km/s). A Monte Carlo analysis is performed to characterize the effect of dust particle impacts on the attitude of SC B1, and to evaluate the likelihood of satisfying pointing and angular velocity requirements of the science camera. Analysis initially shows that particles of mass 10−8–10−5 kg represent the most relevant source of perturbation due to their transferred angular momentum and likelihood of being encountered, and saturation of reaction wheels is shown unlikely given the large fly-by speeds and short fly-by durations (20 min–2 h). More detailed analysis ultimately suggests a probability larger than 90% of satisfying science camera requirements despite the extreme, uncertain fly-by conditions, dust environment, and component inaccuracies (star tracker, gyroscopes, and reaction wheels). Results also show that upgrading the reaction wheel that is implemented along the camera line-of-sight can improve, but only marginally, attitude performance, and proper alignment of solar arrays parallel to the incoming flow of particles is shown essential to maximize probability of success.
Published: 2022

2. Direct observations of pure electron outflow in magnetic reconnection

Author: Sakai, K., Moritaka, T., Morita, T., Tomita, K., Minami, T., Nishimoto, T., Egashira, S., Ota, M., Sakawa, Y., Ozaki, N., Kodama, R., Kojima, T., Takezaki, T., Yamazaki, R., Tanaka, S. J., Aihara, K., Koenig, M., Albertazzi, B., Mabey, P., Woolsey, N., Matsukiyo, S., Takabe, H., Hoshino, M., Kuramitsu, Y., Laboratoire pour l'utilisation des lasers intenses (LULI), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS]Physics [physics], Multidisciplinary
Abstract: 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.
Published: 2022

3. Strength of diamond beyond the elastic limit under dynamic compression

Author: Katagiri, K., Ozaki, N., Dresselhaus-Marais, L. E., Eggert, J. H., Inubushi, Y., Irifune, T., Koenig, M., Matsuoka, T., Miyanishi, K., Nakamura, H., Nishiyama, N., Okuchi, T., Sekine, T., Seto, Y., Sueda, K., Tange, Y., Togashi, T., Umeda, Y., Yabashi, M., Yabuuchi, T., and Kodama, R.
Subjects: Condensed Matter - Materials Science, Materials Science (cond-mat.mtrl-sci), FOS: Physical sciences
Abstract: Extremely high pressures over a million of atmospheres are required to deform diamonds permanently. Under dynamic high-pressure conditions, even such strong materials lose their strengths so rapidly that the initially pristine lattice transforms into complex dynamics. Here, we report femtosecond x-ray diffraction observations that directly resolve how shock waves deform the crystal lattice in the isotropic nano-polycrystalline form of diamond. The results show that the nano-grain reinforced diamond retains its strength at shock pressures far beyond its elastic limit until it finally approaches zero at 707 GPa, indicating the existence of brittle-ductile transition of nano-polycrystalline diamond under high-strain rate shock compression. The atomic-level deformation process of the diamond observed in this study is a key benchmark for designing high strength materials and simulating their behavior under extreme conditions.
Published: 2022

4. X-ray diffraction study of phase transformation dynamics of Fe and Fe-Si alloys along the shock Hugoniot using an x-ray free electron laser

Author: Krygier, A., Harmand, M., Albertazzi, B., McBride, E. E., Miyanishi, K., Antonangeli, D., Inubushi, Y., Kodama, R., Koenig, M., Matsuoka, T., Mogni, G., Pietrucci, F., Saitta, A. M., Togashi, T., Umeda, Y., Vinci, T., Yabashi, M., Yabuuchi, T., Fiquet, G., Ozaki, N., Lawrence Livermore National Laboratory (LLNL), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire pour l'utilisation des lasers intenses (LULI), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci]
Abstract: International audience; The x-ray free electron laser (XFEL) enables probing highly compressed material response at the subnanosecond timescale. We exploit the ultrafast XFEL pulse to combine reflection x-ray diffraction and laserdriven shock compression to perform a study of phase transformation and stability in iron and Fe-Si alloys. Our approach enables us to observe that solid-solid phase transformations occur in iron and Fe-Si8.5wt% in ≤130 ps at ∼130 GPa; no transformation is observed in Fe-Si16wt% up to 110 GPa. Density Functional Theory calculations predict similar phase relations.
Published: 2022

5. Rare coding variation provides insight into the genetic architecture and phenotypic context of autism

Author: J. M., Fu, Satterstrom, F. K., Peng, M., Brand, H., Collins, R. L., Dong, S., Wamsley, B., Klei, L., Wang, L., Hao, S. P., Stevens, C. R., Cusick, C., Babadi, M., Banks, E., Collins, B., Dodge, S., Gabriel, S. B., Gauthier, L., Lee, S. K., Liang, L., Ljungdahl, A., Mahjani, B., Sloofman, L., Smirnov, A. N., Barbosa, M., Betancur, C., Brusco, A., Chung, B. H. Y., Cook, E. H., Cuccaro, M. L., Domenici, E., Ferrero, G. B., Gargus, J. J., Herman, G. E., Hertz-Picciotto, I., Maciel, P., Manoach, D. S., Passos-Bueno, M. R., Persico, A., Renieri, A., Sutcliffe, J. S., Tassone, F., Trabetti, E., Campos, G., Cardaropoli, S., Carli, D., Chan, M. C. Y., Fallerini, C., Giorgio, E., Girardi, A. C., Hansen-Kiss, E., Lee, S. L., Lintas, C., Ludena, Y., Nguyen, R., Pavinato, L., Pericak-Vance, M., Pessah, I. N., Schmidt, R. J., Smith, M., Costa, C. I. S., Trajkova, S., Wang, J. Y. T., M. H. C., Yu, Aleksic, B., Artomov, M., Benetti, E., Biscaldi-Schafer, M., Borglum, A. D., Carracedo, A., Chiocchetti, A. G., Coon, H., Doan, R. N., Fernandez-Prieto, M., Freitag, C. M., Gerges, S., Guter, S., Hougaard, D. M., Hultman, C. M., Jacob, S., Kaartinen, M., Kolevzon, A., Kushima, I., Lehtimaki, T., Rizzo, C. L., Maltman, N., Manara, M., Meiri, G., Menashe, I., Miller, J., Minshew, N., Mosconi, M., Ozaki, N., Palotie, A., Parellada, M., Puura, K., Reichenberg, A., Sandin, S., Scherer, S. W., Schlitt, S., Schmitt, L., Schneider-Momm, K., Siper, P. M., Suren, P., Sweeney, J. A., Teufel, K., del Pilar Trelles, M., Weiss, L. A., Yuen, R., Cutler, D. J., De Rubeis, S., Buxbaum, J. D., Daly, M. J., Devlin, B., Roeder, K., Sanders, S. J., Talkowski, M. E., Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Carnegie Mellon University [Pittsburgh] (CMU), Harvard Medical School [Boston] (HMS), University of California [San Francisco] (UC San Francisco), University of California (UC), University of California [Los Angeles] (UCLA), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, The University of Hong Kong (HKU), University of Illinois [Chicago] (UIC), University of Illinois System, University of Miami Leonard M. Miller School of Medicine (UMMSM), University of Trento [Trento], University of California [Irvine] (UC Irvine), Nationwide Children's Hospital, University of California [Davis] (UC Davis), Universidade do Minho = University of Minho [Braga], Massachusetts General Hospital [Boston, MA, USA], Escola Politecnica da Universidade de Sao Paulo [Sao Paulo], Università degli Studi di Messina = University of Messina (UniMe), Università degli Studi di Siena = University of Siena (UNISI), Azienda Ospedaliera Universitaria Senese, Vanderbilt University [Nashville], Vanderbilt University School of Medicine [Nashville], Università degli studi di Verona = University of Verona (UNIVR), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), Emory University School of Medicine, Emory University [Atlanta, GA], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Autism Sequencing Consortium (ASC), Broad Institute Center for Common Disease Genomics (Broad-CCDG), iPSYCH-BROAD Consortium : Branko Aleksic, Mykyta Artomov, Elisa Benetti, Monica Biscaldi-Schafer, Anders D Børglum, Angel Carracedo, Andreas G Chiocchetti, Hilary Coon, Ryan N Doan, Montserrat Fernández-Prieto, Christine M Freitag, Sherif Gerges, Stephen Guter, David M Hougaard, Christina M Hultman, Suma Jacob, Miia Kaartinen, Alexander Kolevzon, Itaru Kushima, Terho Lehtimäki, Caterina Lo Rizzo, Nell Maltman, Marianna Manara, Gal Meiri, Idan Menashe, Judith Miller, Nancy Minshew, Matthew Mosconi, Norio Ozaki, Aarno Palotie, Mara Parellada, Kaija Puura, Abraham Reichenberg, Sven Sandin, Stephen W Scherer, Sabine Schlitt, Lauren Schmitt, Katja Schneider-Momm, Paige M Siper, Pål Suren, John A Sweeney, Karoline Teufel, Maria Del Pilar Trelles, Lauren A Weiss, Ryan Yuen., and Betancur, Catalina
Subjects: Broad Institute Center for Common Disease Genomics, Autism Sequencing Consortium, DNA Copy Number Variations, Autism Spectrum Disorder, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Autism, Intellectual and Developmental Disabilities (IDD), iPSYCH-BROAD Consortium, autism spectrum disorders, disease gene, copy number variants, neuropsychiatric disorders, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, GENOMAS, Medical and Health Sciences, Article, Clinical Research, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Autistic Disorder, Aetiology, Genetic association study, Pediatric, Human Genome, Neurodevelopmental disorders, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Biological Sciences, Autism spectrum disorders, Brain Disorders, Mental Health, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Gene expression, Biotechnology, Developmental Biology
Abstract: International audience; Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.
Published: 2022

6. Direct imaging of shock wave splitting in diamond at Mbar pressures

Author: Makarov, S. S., Dyachkov, S. A., Pikuz, T. A., Katagiri, K., Zhakhovsky, V. V., Inogamov, N. A., Khokhlov, V. A., Martynenko, A. S., Albertazzi, B., Rigon, G., Mabey, P., Hartley, N., Inubushi, Y., Miyanishi, K., Sueda, K., Togashi, T., Yabashi, M., Yabuuchi, T., Kodama, R., Pikuz, S. A., Koenig, M., and Ozaki, N.
Subjects: Plasma Physics (physics.plasm-ph), Condensed Matter - Materials Science, Materials Science (cond-mat.mtrl-sci), FOS: Physical sciences, Physics - Plasma Physics
Abstract: The propagation of a shock wave in solids can stress them to ultra-high pressures of millions of atmospheres. Understanding the behavior of matter at these extreme pressures is essential to describe a wide range of physical phenomena, including the formation of planets, young stars and cores of super-Earths, as well as the behavior of advanced ceramic materials subjected to such stresses. Under megabar (Mbar) pressure, even a solid with high strength exhibits plastic properties, causing the shock wave to split in two. This phenomenon is described by theoretical models, but without direct experimental measurements to confirm them, their validity is still in doubt. Here, we present the results of an experiment in which the evolution of the coupled elastic-plastic wave structure in diamond was directly observed and studied with submicron spatial resolution, using the unique capabilities of the X-ray free-electron laser. The direct measurements allowed, for the first time, the fitting and validation of a strength model for diamond in the range of several Mbar by performing continuum mechanics simulations in 2D geometry. The presented experimental approach to the study of shock waves in solids opens up new possibilities for the direct verification and construction of the equations of state of matter in the ultra-high pressure range, which are relevant for the solution of a variety of problems in high energy density physics., Comment: 14 pages, 15 figures, submitted to Nature
Published: 2022
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7. In Situ Characterization of XFEL Beam Intensity Distribution and Focusability by High-Resolution LiF Crystal Detector

Author: A., Pikuz T., Ya., Faenov A., Matsuoka, T., Albertazzi, B., Ozaki, N., Hartely, N., Muray, Ricardo Arturo O., Yabuuchi, T., Habara, H., Matsuyama, S., Yamauchi, K., Inubushi, Y., Togashi, T., yumoto, H., Tange, Y., Tono, K., Sato, Y., Yabashi, M., Mitrofanov, A., A., Pikuz S., Bleiner, D., Grum-Grzhimailo, A., N., Rosanov N., V., Vysotina N., Harmand, M., Koenig, M., A., Tanaka K., and Ishikawa, T.
Abstract: We present here a new diagnostics based on using LiF crystal detectors that are able to perform measurements an intensity distribution of X-rays beams with diameters ranging from some microns up to some centimeters with high spatial resolution (~1 micron). in situ, 3D visualization of SACLA XFEL focused beam profile along propagation, including propagation inside photoluminescence solid materials, is demonstrated.
Published: 2018

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

Author: Ruiz-Lopez, M., Faenov, A., Pikuz, T., Ozaki, N., Mitrofanov, A., Albertazzi, B., Hartley, N., Matsuoka, T., Ochante, Y., Tange, Y., Yabuuchi, T., Habara, T., A., Tanaka K., Inubushi, Y., Yabashi, M., Nishikino, M., Kawachi, T., Pikuz, S., Ishikawa, T., and Kodama, R.
Subjects: Physics::Instrumentation and Detectors, Physics::Optics, Physics::Accelerator Physics
Abstract: 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.
Published: 2017

9. Ultrafast Anisotropic Disordering in Graphite Driven by Intense Hard X-ray Pulses

Author: Hartley, N. J., Grenzer, J., Makita, M., Matsuoka, T., Medvedev, N., Nakajima, S., Ozaki, N., Pikuz, T., Rode, A. V., Rohatsch, K., Sagae, D., Schuster, A. K., Lu, W., Tono, K., Vorberger, J., Yabuuchi, T., Kraus, D., Huang, L. G., Inubushi, Y., Kamimura, N., Katagiri, K., Kodama, R., Kon, A., and Lipp, V.
Subjects: ddc:530
Abstract: High energy density physics 32, 63 - 69 (2019). doi:10.1016/j.hedp.2019.05.002, We present results from the SPring-8 Angstrom Compact free electron LAser (SACLA) X-ray free electron laser (XFEL) facility, using an X-ray pump, X-ray probe scheme to observe ultrafast changes in the structure of heated graphite. The 9.8 keV XFEL beam was focused to give an intensity on the order of ∼ 10$^{19}$ W/cm$^2$, and the evolution of the diffraction pattern observed up to delays of 300 fs. The interplanar diffraction peaks weaken significantly within 10s of femtoseconds, but in-plane diffraction orders i.e. those with Miller Index $(hk0)$, persist up to 300 fs, with the observed signal increasing. We interpret this as nonthermal damage through the breaking of interplanar bonds, which at longer timescales leads to ablation by removal of intact graphite sheets. Post-experiment examination of the graphite samples shows damage which is comparable in size to the range of the excited photoelectrons. These results highlight the challenges of accurately modelling X-ray driven heating, as it becomes a routine approach to generating high energy density states., Published by Elsevier, Amsterdam [u.a.]
Published: 2019

10. Kinetic Simulations of Target Heating, Ionization and Micro-Explosion with High Intensity XFEL Beams

Author: Huang, L., Hartley, N., Hau-Riege, S., Inubushi, Y., Kamimura, N., Katagiri, K., Kodama, R., Kon, A., Makita, M., Matsuoka, T., Nakajima, S., Pikuz, T., Rode, A., Rohatsch, K., Sagae, D., Schuster, A., Tono, K., Lu, W., Yabuuchi, T., Ozaki, N., Kraus, D., and Cowan, T.
Subjects: Pump-Probe Experiment, Kinect Simulations, XFEL, Radiation Transport, Physics::Atomic and Molecular Clusters
Abstract: High intensity X-ray Free Electron Lasers (XFEL) are an ideal tool to heat materials directly and isochorically, which can cause them to be modified and damaged irreversibly. During XFEL-matter interactions, the energy of an XFEL beam will be mainly absorbed by photoionization, creating numerous high-energy photo- and Auger electrons. Modelling this process is quite complex since both atomic physics and plasma physics are involved. Atomic collisional-radiative (CR) codes such as FLYCHK are widely used to simulate such processes. However, the CR codes typically assume local thermodynamic equilibrium (LTE) and are limited to zero dimension. In order to understand the sample damaging mechanisms, we performed two-dimensional kinetic particle-in-cell simulations with radiation transport (PIC-RT) to retrieve the temporal processes of XFEL-matter interactions. The dynamics of XFEL-Matter interactions can roughly divide into three different time scales: 1) electron heating and photoionization by XFEL in ~ 10 fs ; 2) collisional heating and ionization by high-energy photo- and Auger electrons with several keV energy in tens of fs to sub-ps; and 3) collective hydrodynamic explosion driven by ~ TPa thermal pressure from ~100 fs to nanoseconds. The simulation results are compared to our recent experiment that a variety of samples were irradiated by Japanese XFEL SACLA with intensities on the order of 10^20 W/cm^2. The post-analysis of the irradiated samples showed that large holes with radius sizes more than one order of magnitude higher than the XFEL spot were created for metallic samples. The hole size is also much larger than the stopping range of high energy electrons. According to our PIC-RT simulations, we attribute the generation of such large holes to the micro-explosion process. Kinect simulation of the hole generation with multiple time scales is also useful and complementary to understand the change of X-Ray diffraction pattern in the experiment that infers significant material structural change on femtosecond timescales.
Published: 2019

11. Equation of state and optical properties of shock-compressed C:H:N:O molecular mixtures

Author: Guarguaglini, M., Hernandez, J. -A., Okuchi, T., Barroso, P., Benuzzi-Mounaix, A., Bolis, R., Brambrink, E., Fujimoto, Y., Kodama, R., Koenig, M., Lefevre, F., Miyanishi, K., Ozaki, N., Sano, T., Umeda, Y., Vinci, T., and Ravasio, A.
Subjects: Earth and Planetary Astrophysics (astro-ph.EP), FOS: Physical sciences, Astrophysics::Earth and Planetary Astrophysics, Astrophysics - Earth and Planetary Astrophysics
Abstract: Water, ethanol, and ammonia are the key components of the mantles of Uranus and Neptune. To improve structure and evolution models and give an explanation of the magnetic fields and luminosities of the icy giants, those components need to be characterised at planetary conditions (some Mbar and a few $10^3$ K). Those conditions are typical of the Warm Dense Matter regime, which exhibits a rich phase diagram, with the coexistence of many states of matter and a large variety of chemical processes. H$_2$O, C:H:O, and C:H:N:O mixtures have been compressed up to 2.8 Mbar along the principal Hugoniot using laser-driven decaying shocks. The experiments were performed at the GEKKO XII and LULI 2000 laser facilities using standard optical diagnostics (Doppler velocimetry and pyrometry) to characterise equation of state and optical reflectivity of the shocked states. The results show that H$_2$O and the C:H:N:O mixture share the same equation of state with a density scaling, while the reflectivity behaves differently by what concerns both the onset pressures and the saturation values. The reflectivity measurement at two frequencies allows to estimate the conductivity and the complex refractive index using a Drude model.
Published: 2018

12. Experimental platform for the investigation of magnetized-reverse-shock dynamics in the context of POLAR

Author: Gregori, G, Albertazzi, B, Falize, E, Pelka, A, Brack, F, Kroll, F, Yurchak, R, Brambrink, E, Mabey, P, Ozaki, N, Pikuz, S, Van Box Som, L, Bonnet-Bidaud, J, Cross, J, Filippov, E, Kodama, R, Mouchet, M, Morita, T, Sakawa, Y, Drake, R, Kuranz, C, Manuel, M, Li, C, Tzeferacos, P, Lamb, D, Schramm, U, and Koenig, M
Subjects: Shock wave, Nuclear and High Energy Physics, Context (language use), laboratory astrophysics, 01 natural sciences, 010305 fluids & plasmas, symbols.namesake, 0103 physical sciences, accretion processes, polar, Magnetohydrodynamic drive, high-power laser, 010303 astronomy & astrophysics, Physics, Shock (fluid dynamics), Mechanics, Plasma, Atomic and Molecular Physics, and Optics, Electronic, Optical and Magnetic Materials, Magnetic field, Nuclear Energy and Engineering, Mach number, hydrodynamics, symbols, Polar, radiative shocks
Abstract: The influence of a strong external magnetic field on the collimation of a high Mach number plasma flow and its collision with a solid obstacle is investigated experimentally and numerically. The laser irradiation ($I\sim 2\times 10^{14}~\text{W}\cdot \text{cm}^{-2}$) of a multilayer target generates a shock wave that produces a rear side plasma expanding flow. Immersed in a homogeneous 10 T external magnetic field, this plasma flow propagates in vacuum and impacts an obstacle located a few mm from the main target. A reverse shock is then formed with typical velocities of the order of 15–20 $\pm$ 5 km/s. The experimental results are compared with 2D radiative magnetohydrodynamic simulations using the FLASH code. This platform allows investigating the dynamics of reverse shock, mimicking the processes occurring in a cataclysmic variable of polar type.
Published: 2018
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13. Simultaneous 8.2 keV phase-contrastimaging and 24.6 keV X-ray diffraction fromshock-compressed matter at the LCLS

Author: Seiboth, F., Fletcher, L. B., Mcgonegle, D., Anzellini, S., Dresselhaus-Cooper, L. E., Frost, M., Galtier, E., Goede, S., Harmand, M., Lee, H. J., Levitan, A. L., Miyanishi, K., Nagler, B., Nam, I., Ozaki, N., Rödel, M., Schropp, A., Spindloe, C., Sun, P., Wark, J. S., Hastings, J., Glenzer, S. H., and Mcbride, E. E.
Subjects: germanium, LCLS, x-ray diffraction, Phase Contrast Imaging, shock compression, XFEL, MEC, PCI, shock, Matter in Extreme Conditions, release
Abstract: In this work, we demonstrate simultaneous phase-contrast imaging (PCI) and X-ray diffractionfrom shock compressed matter at the Matter in Extreme Conditions endstation, at the LinacCoherent Light Source (LCLS). We utilize the chromaticity from compound refractive X-ray lensesto focus the 24.6 keV 3rd order undulator harmonic of the LCLS to a spot size of 5lm on target toperform X-ray diffraction. Simultaneous PCI from the 8.2 keV fundamental X-ray beam is used tovisualize and measure the transient properties of the shock wave over a 500lm field of view.Furthermore, we demonstrate the ability to extend the reciprocal space measurements by 5 Angstroem, rel-ative to the fundamental X-ray energy, by utilizing X-ray diffraction from the 3rd harmonic of theLCLS.
Published: 2018

14. Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Author: Lim, Elaine T., Uddin, Mohammed, De Rubeis, Silvia, Chan, Yingleong, Kamumbu, Anne S., Zhang, Xiaochang, D'Gama, Alissa M., Kim, Sonia N., Hill, Robert Sean, Goldberg, Arthur P., Poultney, Christopher, Minshew, Nancy J., Kushima, Itaru, Aleksic, Branko, Ozaki, Norio, Parellada, Mara, Arango, Celso, Penzol, Maria J., Carracedo, Angel, Kolevzon, Alexander, Hultman, Christina M., Weiss, Lauren A., Fromer, Menachem, Chiocchetti, Andreas G., Freitag, Christine M., Church, George M., Scherer, Stephen W., Buxbaum, Joseph D., Walsh, Christopher A, Aleksic, B, Anney, R, Barbosa, M, Barrett, J, Betancur, C, Bishop, S, Brusco, A, Buxbaum, Jd, Carracedo, A, Chiocchetti, Ag, Chung, Bhy, Cook, E, Coon, H, Cutler, Dj, Daly, M, De Rubeis, S, Doan, R, Fernández-Prieto, M, Ferrero, Gb, Freitag, Cm, Fromer, M, Gargus, J, Geschwind, D, Gill, M, Gómez-Guerrero, L, Hansen-Kiss, E, He, X, Herman, G, Hertz-Picciotto, I, Hultman, C, Iliadou, B, Ionita-Laza, I, Jugessur, A, Knudsen, Gp, Kolevzon, A, Kosmicki, J, Kushima, I, Lee, Sl, Lehner, T, Lennertz, S, Lim, E, Maciel, P, Magnus, P, Manoach, D, Minshew, N, Morrow, E, Mulle, J, Neale, B, Ozaki, N, Palotie, A, Parellada, M, Passos-Bueno, Mr, Pericak-Vance, M, Persico, A, Pessah, I, Reichenberg, A, Reichert, J, Renieri, A, Robinson, E, Samocha, K, Sanders, S, Sandin, S, Santangelo, Sl, Satterstrom, K, Schafer, C, Schellenberg, G, Scherer, S, Senthil, G, Silva, M, Singh, T, Siper, Pm, Soares, G, Stevens, C, Stoltenberg, C, Surén, P, Sutcliffe, Js, Szatmari, P, Tassone, F, Thurm, A, Walsh, C, Weiss, L, Werling, D, Willsey, J, Xu, X, Yu, Tw, Yuen, R, Zwick, Me., Howard Hughes Medical Institute [Boston] (HHMI), Howard Hughes Medical Institute (HHMI)-Harvard Medical School [Boston] (HMS), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard University [Cambridge], Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Nagoya University, Hospital General Universitario 'Gregorio Marañón' [Madrid], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Universidade de Santiago de Compostela [Spain] (USC ), CIBER de Enfermedades Raras (CIBERER), Fundación Pública Galega Medicina Xenómica - SERGAS [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), CIBER de Enfermedades Raras (CIBERER)-Universidade de Santiago de Compostela [Spain] (USC ), King Abdulaziz University, Karolinska Institutet [Stockholm], University of California [San Francisco] (UCSF), University of California, Goethe-University Frankfurt am Main, Génétique de l'autisme = Genetics of Autism (NPS-01), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Hospital for sick children [Toronto] (SickKids), University of Toronto, McLaughlin Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], Autism Sequencing Consortium: Branko Aleksic, Richard Anney, Mafalda Barbosa, Jeffrey Barrett, Catalina Betancur, Somer Bishop, Alfredo Brusco, Joseph D Buxbaum, Angel Carracedo, Andreas G Chiocchetti, Brian H Y Chung, Edwin Cook, Hilary Coon, David J Cutler, Mark Daly, Silvia De Rubeis, Ryan Doan, Montserrat Fernández-Prieto, Giovanni Battista Ferrero, Christine M Freitag, Menachem Fromer, Jay Gargus, Dan Geschwind, Michael Gill, Lorena Gómez-Guerrero, Emily Hansen-Kiss, Xin He, Gail Herman, Irva Hertz-Picciotto, Christina Hultman, Bozenna Iliadou, Iuliana Ionita-Laza, Anil Jugessur, Gun Peggy Knudsen, Alexander Kolevzon, Jack Kosmicki, Itaru Kushima, S L Lee, Thomas Lehner, Savannah Lennertz, Elaine Lim, Patricia Maciel, Per Magnus, Dara Manoach, Nancy Minshew, Eric Morrow, Jennifer Mulle, Benjamin Neale, Norio Ozaki, Aarno Palotie, Mara Parellada, Maria Rita Passos-Bueno, Margaret Pericak-Vance, Antonio Persico, Isaac Pessah, Avi Reichenberg, Jennifer Reichert, Alessandra Renieri, Elise Robinson, Kaitlin Samocha, Stephan Sanders, Sven Sandin, Susan L Santangelo, Kyle Satterstrom, Chad Schafer, Gerry Schellenberg, Stephen Scherer, Geetha Senthil, Marisol Silva, Tarjinder Singh, Paige M Siper, Gabriela Soares, Christine Stevens, Camilla Stoltenberg, Pål Surén, James S Sutcliffe, Peter Szatmari, Flora Tassone, Audrey Thurm, Christopher Walsh, Lauren Weiss, Donna Werling, Jeremy Willsey, Xinyi Xu, Timothy W Yu, Ryan Yuen, Michael E Zwick., University of California [San Francisco] (UC San Francisco), University of California (UC), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Betancur, Catalina
Subjects: 0301 basic medicine, Proband, Nonsynonymous substitution, Autism Spectrum Disorder, Databases, Genetic, Genetic Predisposition to Disease, Genetic Variation, Humans, Mosaicism, Mutation, Missense, Zygote, Neuroscience (all), Mutation, Missense, Epigenetics of autism, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, medicine.disease_cause, Article, 03 medical and health sciences, Genetic variation, mental disorders, Databases, Genetic, medicine, Missense mutation, Heritability of autism, MESH: Genetic Variation, MESH: Databases, Genetic, Genetics, MESH: Autism Spectrum Disorder, MESH: Mutation, Missense, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, General Neuroscience, MESH: Genetic Predisposition to Disease, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Autism spectrum disorder, MESH: Zygote, MESH: Mosaicism
Abstract: International audience; We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 × 10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.
Published: 2017

15. Assessment of antitumor activity and acute peripheral neuropathy of 1,2-diaminocyclohexane platinum (II)-incorporating micelles (NC-4016)

Author: Ueno T, Endo K, Hori K, Ozaki N, Tsuji A, Kondo S, Wakisaka N, Murono S, Kataoka K, Kato Y, and Yoshizaki T
Subjects: Medicine (General), R5-920
Abstract: Takayoshi Ueno,1 Kazuhira Endo,1 Kiyomi Hori,2 Noriyuki Ozaki,2 Akira Tsuji,1 Satoru Kondo,1 Naohiro Wakisaka,1 Shigeyuki Murono,1 Kazunori Kataoka,3,4 Yasuki Kato,5 Tomokazu Yoshizaki11Division of Otolaryngology-Head and Neck Surgery, 2Department of Functional Anatomy, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan; 3Department of Materials Engineering, Graduate School of Engineering, 4Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 5Research Division, NanoCarrier Co., Ltd, Chiba, JapanAbstract: Oxaliplatin, a third-generation platinum compound incorporating oxalate and1,2-diaminocyclohexane platinum, has been widely used in chemotherapy regimens for the treatment of metastatic colorectal cancer. Because of its wide spectrum of antitumor activity, oxaliplatin has been applied for the treatment of other carcinomas. However, the antitumor activity of single-agent oxaliplatin is insufficient. To increase its antitumor effects, polymeric micellar nanoparticles incorporating1,2-diaminocyclohexane platinum (NC-4016) have been developed. The present study was designed to evaluate the efficacy of NC-4016and its association with peripheral neuropathy, which is a primary dose-limiting factor in oxaliplatin therapy. The in vitro antitumor activity of NC-4016was investigated using human carcinoma cell lines. To investigate the antitumor effects of NC-4016in vivo, nude mice bearing the human carcinoma cell line KB were administered NC-4016or oxaliplatin. The in vitro growth-inhibiting effect of NC-4016was significantly weaker than that of oxaliplatin. However, the antitumor efficacy of NC-4016was superior to that of oxaliplatin in vivo. Moreover, we compared the severity of peripheral neuropathy induced by oxaliplatin and NC-4016in a rat model. Oxaliplatin, NC-4016, or5% glucose (control) were administered by a single tail vein injection. In the oxaliplatin-treated rats, neither mechanical nor heat allodynia was observed during the experimental period, whereas cold hyperalgesia/allodynia was observed from day1to7. Conversely, cold hyperalgesia/allodynia was not observed in the NC-4016-treated rats. The present study demonstrated that the antitumor efficacy of NC-4016was superior to that of oxaliplatin in a mouse model of human carcinoma cell line KB. In addition, NC-4016-treated rats did not develop acute cold hypersensitivity, which is frequently experienced by patients after oxaliplatin administration.Keywords: oxaliplatin, carcinoma, chemotherapy, drug delivery system
Published: 2014

16. Decaying shock studies of phase transitions in MgO-SiO 2 systems: Implications for the super-Earths' interiors

Author: Bolis, R., Morard, G., Vinci, T., Ravasio, A., Bambrink, E., Guarguaglini, M., Koenig, M., Musella, R., Remus, F., Bouchet, J., Ozaki, N., Miyanishi, K., Sekine, T., Sakawa, Y., Sano, T., Kodama, R., Guyot, F., Benuzzi-Mounaix, A., Laboratoire pour l'utilisation des lasers intenses (LULI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Univers et Théories (LUTH (UMR_8102)), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Mécanique Céleste et de Calcul des Ephémérides (IMCCE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Osaka University [Osaka], Institut de minéralogie et de physique des milieux condensés (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Sorbonne Université (SU)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and PSL Research University (PSL)-PSL Research University (PSL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS]Physics [physics], [SDU]Sciences of the Universe [physics], [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

17. Decaying shock studies of phase transitions in MgOSiO2 systems: implications for the Super-Earths interiors

Author: Bolis, R. M., Morard, G., Vinci, T., Ravasio, A., Bambrink, E., Guarguaglini, M., Koenig, M., Musella, R., Remus, F., Bouchet, J., Ozaki, N., Miyanishi, K., Sekine, T., Sakawa, Y., Sano, T., Kodama, R., Guyot, F., and Benuzzi-Mounaix, A.
Subjects: Earth and Planetary Astrophysics (astro-ph.EP), Physics - Geophysics, FOS: Physical sciences, Geophysics (physics.geo-ph), Astrophysics - Earth and Planetary Astrophysics
Abstract: We report an experimental study of the phase diagrams of periclase (MgO), enstatite (MgSiO3) and forsterite (Mg2SiO4) at high pressures. We investigated with laser driven decaying shocks the pressure/temperature curves of MgO, MgSiO3 and Mg2SiO4 between 0.2-1.2 TPa, 0.12-0.5 TPa and 0.2-0.85 TPa respectively. A melting signature has been observed in MgO at 0.47 TPa and 9860 K, while no phase changes were observed neither in MgSiO3 nor in Mg2SiO4. An increasing of reflectivity of MgO, MgSiO3 and Mg2SiO4 liquids have been detected at 0.55 TPa -12 760 K, 0.15 TPa - 7540 K, 0.2 TPa - 5800 K, respectively. In contrast to SiO2, melting and metallization of these compounds do not coincide implying the presence of poor electrically conducting liquids close to the melting lines. This has important implications for the generation of dynamos in Super-earths mantles.
Published: 2016

18. Melting of iron close to Earth's inner core boundary conditions and beyond

Author: Harmand, M., Ravasio, A., Mazevet, S., Bouchet, J., Denoeud, A., Dorchies, F., Feng, Y., Fourment, C., Galtier, E ., Gaudin, J., Guyot, F., Kodama, R., Koenig, M., Lee, H. J., Miyanishi, K., Morard, G., Musella, R., Nagler, B., Nakatsutsumi, M., Ozaki, N., Recoules, V., Toleikis, S., Vinci, T., Zastrau, U., Zhu, D., and Benuzzi-Mounaix, A.
Subjects: Physics - Geophysics, Condensed Matter - Materials Science, Materials Science (cond-mat.mtrl-sci), FOS: Physical sciences, Geophysics (physics.geo-ph)
Abstract: Several important geophysical features such as heat flux at the Core-Mantle Boundary or geodynamo production are intimately related with the temperature profile in the Earth's core. However, measuring the melting curve of iron at conditions corresponding to the Earth inner core boundary under pressure of 330 GPa has eluded scientists for several decades. Significant discrepancies in previously reported iron melting temperatures at high pressure have called into question the validity of dynamic measurements. We report measurements made with a novel approach using X-ray absorption spectroscopy using an X-ray free electron laser source coupled to a laser shock experiment. We determine the state of iron along the shock Hugoniot up to 420 GPa (+/- 50) and 10800 K (+/- 1390) and find an upper boundary for the melting curve of iron by detecting solid iron at 130 GPa and molten at 260, 380 and 420 GPa along the shock Hugoniot. Our result establishes unambiguous agreement between dynamic measurement and recent extrapolations from static data thus resolving the long-standing controversy over the reliability of using dynamic compression to study the melting of iron at conditions close to the Earth's inner core boundary and beyond., 9 pages 3 figures
Published: 2014

19. 'Experimental studies of planetary cores'

Author: Guillaume Morard, Antonangeli D., Amadou N., Brambrink E., Tommaso Vinci, Benuzzi-Mounaix A., Huser G., Brygoo S., Guyot F., De Resseguier T., Mazevet S., Miyanishi K., Ozaki N., Kodama R., Henry O., Raffestin D., Boehly T., Koenig M., Mezouar M., Denis Andrault, Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), and Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS)
Subjects: ComputingMilieux_MISCELLANEOUS, [SDU.STU.MI]Sciences of the Universe [physics]/Earth Sciences/Mineralogy
Abstract: International audience
Published: 2014

20. Normal values and age-dependent changes in GTP cyclohydrolase I activity in stimulated mononuclear blood cells measured by high-performance liquid chromatography

Author: Hibiya, M., Ichinose, Hiroshi, Ozaki, N., Fujita, K., Nishimoto, T., Yoshikawa, T., Asano, Y., and Nagatsu, T.
Subjects: Male, GTP cyclohydrolase I, Stimulation, High-performance liquid chromatography, Peripheral blood mononuclear cell, Blood cell, Sex Factors, Reference Values, medicine, Humans, Phytohemagglutinins, GTP Cyclohydrolase, Chromatography, High Pressure Liquid, chemistry.chemical_classification, Chromatography, biology, Chemistry, Age Factors, General Chemistry, Tetrahydrobiopterin, medicine.anatomical_structure, Enzyme, Leukocytes, Mononuclear, biology.protein, Female, Quantitative analysis (chemistry), medicine.drug
Abstract: GTP cyclohydrolase I (GCH1) activity in phytohemaglutinin (PHA)-stimulated mononuclear blood cells (MBCs) is a useful clinical marker for diagnosis of tetrahydrobiopterin (BH 4 )-related genetic disorders such as recessively inherited GCH1 deficiency and dominantly inherited dopa-responsive dystonia (Segawa’s disease). Since the assay is complex, including isolation of MBCs from blood, stimulation of MBCs by PHA under culture, isolation of the protein fraction from the PHA-stimulated MBCs, and the subsequent activity measurement, the reproducibility is problematic in its application to clinical study. We established a sensitive and reproducible method by high-performance liquid chromatography with fluorescence detection for clinical assay of GCH1 in PHA-stimulated MBCs, and measured the normal values of 91 healthy males and females of various ages (1–74 years). The mean normal values were 19.1±0.9 pmol/mg protein per h (mean±S.E., n =91). There were no significant differences between males and females. The activity tends to be higher in the first decade and to be decreased from the second to third decade and becomes almost stable from the third decade.
Published: 2000

21. GTP cyclohydrolase 1 gene haplotypes as predictors of SSRI response in Japanese patients with major depressive disorder

Author: Kishi, T., Ichinose, Hiroshi, Yoshimura, R., Fukuo, Y., Kitajima, T., Inada, T., Kunugi, H., Kato, T., Yoshikawa, T., Ujike, H., Musso, G.M., Umene-Nakano, W., Nakamura, J., Ozaki, N., and Iwata, N.
Subjects: Oncology, Adult, Male, Candidate gene, medicine.medical_specialty, Bipolar Disorder, Genotype, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Asian People, Gene Frequency, Internal medicine, mental disorders, Genetic model, medicine, Humans, Bipolar disorder, GTP Cyclohydrolase, Allele frequency, Genetics, Depressive Disorder, Major, Case-control study, Hamilton Rating Scale for Depression, Middle Aged, medicine.disease, Antidepressive Agents, Psychiatry and Mental health, Clinical Psychology, Logistic Models, Phenotype, Mood disorders, Haplotypes, Fluvoxamine, Case-Control Studies, Major depressive disorder, Female, Psychology, Selective Serotonin Reuptake Inhibitors
Abstract: Background Tetrahydrobiopterin (BH4) plays an important role in the biosynthesis of serotonin, melatonin and catecholamines, all of which are implicated in the pathophysiology of mood disorders (MDs), including major depressive disorder (MDD) and bipolar disorder (BP). Production of BH4 is regulated by GTP cyclohydrolase transcription and activity. Thus, we considered the GTP cyclohydrolase gene ( GCH1 ) to be a good candidate gene in the pathophysiology of MDs and of the serotonin selective reuptake inhibitors (SSRIs) response in MDD, and conducted a case-control study utilizing three SNPs (rs8007267, rs3783641 and rs841) and moderate sample sizes (405 MDD patients, including 262 patients treated by SSRIs, 1022 BP patients and 1805 controls). Method A multiple logistic regression analysis was carried out to compare the frequencies of each SNP genotype for the target phenotype across patients and controls in several genetic models, while adjusting for possible confounding factors. A clinical response was defined as a decrease of more than 50% from the baseline score on the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as a SIGH-D score of less than 7 at 8 weeks. Result No associations between three SNPs in GCH1 and MDD or BP were observed; however, GCH1 was associated with SSRI therapeutic response in MDD in all the marker’s haplotype analysis (Global P value=0.0379). Conclusions Results suggest that GCH1 may predict response to SSRI in MDD in the Japanese population. Nevertheless, a replication study using larger samples may be required for conclusive results, since our sample size was small.
Published: 2012

22. Enhanced Hot Electron Localization and Heating in High-Contrast Ultra-Intense Laser Irradiation of Sharp Micro-Cone Targets

Author: Rassuchine, J., DHumières, E., Baton, S. D., Guillou, P., Koenig, M., Fuchs, J., Audebert, P., Kodama, R., Nakatsutsumi, M., Ozaki, N., Batani, D., Morace, A., Redaelli, R., Gremillet, L., Rousseaux, C., Dorchies, F., Fourment, C., Santos, J. J., Adams, J., Korgan, G., Malekos, S., Hansen, S. B., Shepherd, R., Flippo, K., Gaillard, S., Sentoku, Y., and Cowan, T. E.
Abstract: We report experiments demonstrating enhanced coupling efficiencies employing high contrast laser irradiation of nano-fabricated conical targets. Peak temperatures near 200 eV are observed with modest laser energy (10 J), revealing similarities in hot electron localization and material heating to reduced mass targets. Collisional particle-in-cell simulations attribute this enhancement to self-generated resistive magnetic fields forming within the cone wall, which effectively confine the energetic electrons to heat a reduced volume at the cone tip.
Published: 2009

23. Enhanced hot-electron localization and heating in high-contrast ultraintense laser irradiation of microcone targets

Author: Rassuchine, J., Humieres, E. D., Baton, S. D., Guillou, P., Koenig, M., Chahid, M., Perez, F., Fuchs, J., patrick Audebert, Kodama, R., Nakatsutsumi, M., Ozaki, N., Batani, D., Morace, A., Redaelli, R., Gremillet, L., Rousseaux, C., Dorchies, F., Fourment, C., Santos, J. J., Adams, J., Korgan, G., Malekos, S., Hansen, S. B., Shepherd, R., Flippo, K., Sentoku, Y., Cowan, T. E., Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire pour l'utilisation des lasers intenses (LULI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Critical Care Department, Hospital de Sabadell, CIBER Enfermedades Respiratorias, Institut of Applied Physics (IAP), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Graduate School of Engineering, Osaka University, Graduate School of Engineering, Graduate School of Engineering [Suita, Osaka], Osaka University [Osaka], Dipartimento di Fisica 'Giuseppe Occhialini' = Department of Physics 'Giuseppe Occhialini' [Milano-Bicocca], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), DAM Île-de-France (DAM/DIF), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire d'optique appliquée (LOA), École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Osaka University, and Università degli Studi di Milano-Bicocca [Milano] (UNIMIB)
Subjects: [PHYS]Physics [physics], ComputingMilieux_MISCELLANEOUS
Abstract: International audience; no abstract
Published: 2009

24. Study of iron under high pressure conditions using isentropic compression

Author: Wei, H. G., Brambrink, E., Benuzzi-Mounaix, A., Ravasio, A., Guillaume Morard, Rességuier, T., Lescoute, E., Ozaki, N., Miyanishi, K., Zhao, G., Liang, Z. T., Koenig, M., Guyot, F., School of Physics, Shandong University, Laboratoire pour l'utilisation des lasers intenses (LULI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), National Astronomical Observatories, Chinese Academy of Sciences, Chinese Academy of Sciences [Beijing] (CAS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), Laboratoire de combustion et de détonique (LCD), Université de Poitiers-ENSMA-Centre National de la Recherche Scientifique (CNRS), Graduate School of Engineering [Suita, Osaka], Osaka University [Osaka], Institut de minéralogie et de physique des milieux condensés (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Graduate School of Engineering, Osaka University, Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: iron, phase transformation, Isentropic compression, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, PACS : 52.50.Jm, 91.35.Cb, ComputingMilieux_MISCELLANEOUS, [SPI.MAT]Engineering Sciences [physics]/Materials
Abstract: International audience; We use directly driven method to compress the iron along isentropic path. By adjusting the pulse intensity of laser to increase with time, we directly ablated the iron target with laser to achieve isentropic compression. Rear surface velocities of the iron targets were recorded by VISAR (Velocity Interferometer System for Any Reflector). The iron (bcc) to (hcp) phase transformation was clearly observed. Experiment results were compared with simulations
Published: 2009

25. Recent experiment on fast electron transport in ultra-high intensity laser interaction

Author: Batani, D., Baton, S., Koenig, M., Guillou, P., Loupias, B., Vinci, T., Rousseaux, C., Gremillet, L., Morace, A., Redaelli, R., Nakatsutsumi, M., Kodama, R., Ozaki, N., Norimatsu, T., Rassuchine, J., Cowan, T., Dorchies, F., Fourment, C., Santos, J. J., Dipartimento di Fisica 'Giuseppe Occhialini' = Department of Physics 'Giuseppe Occhialini' [Milano-Bicocca], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Laboratoire pour l'utilisation des lasers intenses (LULI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire d'Orsay (IPNO), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Thomas Jefferson National Accelerator Facility (Jefferson Lab), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Graduate School of Engineering, Osaka University, Graduate School of Engineering, Graduate School of Engineering [Suita, Osaka], Osaka University [Osaka], Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'optique appliquée (LOA), École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Azechi, H. and Hammel, B. and Gauthier, J. C., Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), and Osaka University
Subjects: [PHYS]Physics [physics], ComputingMilieux_MISCELLANEOUS
Abstract: International audience; no abstract
Published: 2008

26. Two-dimendional rhombic-lattice grating coupler for oblique incidence in the integrated crystal waveguide slab (poster)

Author: MIZUTANI, A, IKEDA, N, WATANABE, Y, OZAKI, N, TAKATA, Y, KITAGAWA, Y, Van Laere, Frederik, Taillaert, Dirk, Baets, Roel, SUGIMOTO, Y, and ASAKAWA, K
Subjects: Technology and Engineering
Published: 2007

27. Laser-driven shock waves for the study of extreme states of matter

Author: BENUZZI MOUNAIX, A., Koenig, M., Ravasio, A., Vinci, T., Ozaki, N., RABEC LE GLOAHEC, M., Loupias, B., Huser, G., Henry, E., Bouquet, S., Michaut, C., Hicks, D., Mackinnon, A., Patel, P., Park, H. S., LE PAPE, S., Boehly, T., Borghesi, M., Cecchetti, C., Notley, M., Clark, R., Bandyopadhyay, S., Atzeni, Stefano, Schiavi, Angelo, Aglitskiy, Y., Faenov, A., Pikuz, T., Batani, D., and Tanaka, R. DEZULIAN AND K.
Published: 2006

28. Progress in the study of Warm Dense Matter

Author: Koenig, M., Benuzzi-Mounaix, A., Vinci, T., Ozaki, N., Lepape, S., Batani, D., Huser, G., Hall, T., Hicks, D., Mackinnon, A.J., Patel, P.K., Boehly, T., Borghesi, Marco, Kar, Satyabrata, and Romagnani, Lorenzo
Subjects: Nuclear and High Energy Physics, Physics and Astronomy(all), Condensed Matter Physics
Published: 2005

29. Soil constituent facilitated transport of phosphorous from a high-P surface soil

Author: Motoshita, M., Komatsu, T., Møldrup, Per, Jonge, L. W. de, Ozaki, N., and Fukushima, T.
Subjects: Miljøteknologi
Published: 2003

30. Retardation of multiple environmental impact chemicals in soils:Direct measurements by impulse type HPLC micro-colum method

Author: Komatsu, T., Kawashima, H., Motoshita, M., Møldrup, Per, Ozaki, N., and Fukushima, T.
Published: 2002

31. Colloid release velocities in soil columns during short- and long-term multiple irrigation events

Author: Motoshita, M., Komatsu, T., Møldrup, Per, Ozaki, N., Jonge, L. W. de, de Jonge, L W, Moldrup, P, and Jacobsen, O H
Published: 2002

32. JSNP Excellent Presentation Award for CINP2014

Author: Yoshimi, A., Kunimoto, S., Yamada, S., Branko Aleksic, Hirakawa, A., Nagai, T., and Ozaki, N.

33. Femtosecond laser synthesis of high-pressure phases of Si

Author: Tsujino, M., Tomokazu Sano, Ozaki, N., Sakata, O., Okoshi, M., Inoue, N., Kodama, R., and Hirose, A.

34. Maternal mental disorders and pregnancy outcomes: a clinical study in a Japanese population

Author: Hironaka, M., Tomomi Kotani, Sumigama, S., Tsuda, H., Mano, Y., Hayakawa, H., Tanaka, S., Ozaki, N., Tamakoshi, K., and Kikkawa, F.

35. DESTINY+ Low thrust trajectory design from Earth orbit to Asteroids flyby

Author: Yamamoto, T., Ozaki, N., Dei Tos, D. A., Celik, O., Tanaka, Y., Ferran Gonzalez-Franquesa, and Kawakatsu, Y.

36. First-stage genome-wide Sib-pair linkage analysis of schizophrenia in Japanese

Author: Okazaki, Y., Tsujita, T., Arinami, T., Yoshikawa, T., Fukumaki, Y., Inada, T., Someya, T., Mineta, M., Ujike, H., Ozaki, N., Ohara, K., Ohmori, O., Kojima, T., Nanko, S., Sasaki, T., Yoneda, H., Kusumi, I., Fukuzako, H., Akiyosi, J., Arai, H., Harano, M., Kato, T., Masashi Nibuya, Niwa, S., Sora, I., and Tashiro, N.

37. Radiative shocks: New experiments for laboratory astrophysics

Author: Vinci, T., Koenig, M., Alessandra Benuzzi Mounaix, Ozaki, N., Ravasio, A., Boireau, L., Michaut, C., Bouquet, S., Atzeni, S., and Schiavi, A.

38. Radiative shocks and plasma jets as laboratory astrophysics experiments

Author: Koenig, M., Loupias, B., Vinci, T., Ozaki, N., Benuzzi-Mounaix, A., Le Goahec, M. Rabec, Falize, E., Bouquet, S., Michaut, C., Herpe, G., Baroso, P., Nazarov, W., Aglitskiy, Y., Faenov, A. Ya, Pikuz, T., Courtois, C., Woolsey, N. C., Gregory, C. D., Howe, J., Schlavi, A., Stefano Atzeni, Gillaspy, Jd, Curry, Jj, and Wiese, Wl

39. Molecular genetics of mood disorders

Author: Ikeda, M., Tsuyoshi Kitajima, Iwata, N., and Ozaki, N.

40. Promise of preemptive medicine in psychiatry

Author: Oya-Ito, T., Nakamura, Y., Akira Yoshimi, and Ozaki, N.

41. Mission design of Martian moons exploration (MMX)

Author: Kawakatsu, Y., Kuramoto, K., Usui, T., Ikeda, H., Ozaki, N., Nicola Baresi, Ono, G., Imada, T., Shimada, T., Kusano, H., Sawada, H., Ozawa, T., Baba, M., and Otake, H.

42. System definition of Martian Moons Exploration (MMX)

Author: Kawakatsu, Y., Kuramoto, K., Usui, T., Ikeda, H., Yoshikawa, K., Sawada, H., Ozaki, N., Imada, T., Otake, H., Maki, K., Masatsugu Otsuki, Muller, R., Zacny, K., Satoh, Y., Mary, S., Grebenstein, M., Tokaji, A., Yuying, L., Franquesa, F. G., Pushparaj, N., and Chikazawa, T.

43. Optical characterization of lithium fluoride thin-film imaging detectors for monochromatic hard X-rays

Author: M.A. Vincenti, R.M. Montereali, E. Nichelatti, V. Nigro, M. Piccinini, M. Koenig, P. Mabey, G. Rigon, H.J. Dabrowski, Y. Benkadoum, P. Mercere, P. Da Silva, T. Pikuz, N. Ozaki, S. Makarov, S. Pikuz, B. Albertazzi, Vincenti, M. A., Montereali, R. M., Nichelatti, E., Nigro, V., Piccinini, M., Koenig, M., Mabey, P., Rigon, G., Dabrowski, H. J., Benkadoum, Y., Mercere, P., Da Silva, P., Pikuz, T., Ozaki, N., Makarov, S., Pikuz, S., and Albertazzi, B.
Subjects: Materials for solid-state detectors, 500 Naturwissenschaften und Mathematik::530 Physik::530 Physik, X-ray detectors, Materials for solid-state detectors, Solid state detectors, X-ray detectors, Solid state detectors, Instrumentation, Mathematical Physics
Abstract: Lithium fluoride (LiF) crystals and thin films have been successfully investigated as X-ray imaging detectors based on optical reading of visible photoluminescence emitted by stable radiation-induced F2 and F3 + colour centres. In this work, the visible photoluminescence response of optically-transparent LiF film detectors of three different thicknesses, grown by thermal evaporation on Si(100) substrates and irradiated with monochromatic 7 keV X-rays at several doses in the range between 13 and 4.5× 103 Gy, was carefully investigated by fluorescence optical microscopy. For all the film thicknesses, the photoluminescence response linearly depends on the irradiation dose in the investigated dose range. The lowest detected dose, delivered to the thinnest LiF film, only 0.5 μm thick, is estimated 13 Gy. Edge-enhancement imaging experiments, conducted by irradiating LiF film detectors at the same energy placing an Au mesh in front of them at a distance of 15 mm, allowed estimating a spatial resolution of (0.38 ± 0.05) μm, which is comparable to the microscope one. This very high spatial resolution in LiF film radiation detectors based on colour centres photoluminescence is combined with the availability of a wide field of view on large areas.
Published: 2023

44. Direct LiF imaging diagnostics on refractive X-ray focusing at the EuXFEL High Energy Density instrument

Author: Sergey Makarov, Mikako Makita, Motoaki Nakatsutsumi, Tatiana Pikuz, Norimasa Ozaki, Thomas R. Preston, Karen Appel, Zuzana Konopkova, Valerio Cerantola, Erik Brambrink, Jan-Patrick Schwinkendorf, Istvan Mohacsi, Tomas Burian, Jaromir Chalupsky, Vera Hajkova, Libor Juha, Vojtech Vozda, Bob Nagler, Ulf Zastrau, Sergey Pikuz, Makarov, S, Makita, M, Nakatsutsumi, M, Pikuz, T, Ozaki, N, Preston, T, Appel, K, Konopkova, Z, Cerantola, V, Brambrink, E, Schwinkendorf, J, Mohacsi, I, Burian, T, Chalupsky, J, Hajkova, V, Juha, L, Vozda, V, Nagler, B, Zastrau, U, and Pikuz, S
Subjects: Nuclear and High Energy Physics, Radiation, X-ray beam characterization, X-ray free-electron laser, lithium fluoride (LiF) detector, Instrumentation, compound refractive lense, focusing system, X-ray focusing
Abstract: The application of fluorescent crystal media in wide-range X-ray detectors provides an opportunity to directly image the spatial distribution of ultra-intense X-ray beams including investigation of the focal spot of free-electron lasers. Here the capabilities of the micro- and nano-focusing X-ray refractive optics available at the High Energy Density instrument of the European XFEL are reported, as measured in situ by means of a LiF fluorescent detector placed into and around the beam caustic. The intensity distribution of the beam focused down to several hundred nanometers was imaged at 9 keV photon energy. A deviation from the parabolic surface in a stack of nanofocusing Be compound refractive lenses (CRLs) was found to affect the resulting intensity distribution within the beam. Comparison of experimental patterns in the far field with patterns calculated for different CRL lens imperfections allowed the overall inhomogeneity in the CRL stack to be estimated. The precise determination of the focal spot size and shape on a sub-micrometer level is essential for a number of high energy density studies requiring either a pin-size backlighting spot or extreme intensities for X-ray heating.
Published: 2023

45. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Author: Amare, Azmeraw T., Schubert, Klaus Oliver, Hou, Liping, Clark, Scott R., Papiol, Sergi, Cearns, Micah, Heilbronner, Urs, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hsu, Yi Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Del Zompo, Maria, DePaulo, J. Raymond, Étain, Bruno, Jamain, Stephane, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jiménez, Esther, Kahn, Jean Pierre, Kassem, Layla, Kuo, Po Hsiu, Kato, Tadafumi, Kelsoe, John R., Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J., McElroy, Susan L., Colom, Francesc, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Ösby, Urban, Pfennig, Andrea, Potash, James B., Reif, Andreas, Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Blackwood, Douglas H.R., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane varregaard, Clarke, Toni Kim, Coleman, Jonathan R.I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Hickie, Ian B., Homuth, Georg, Horn, Carsten, Hottenga, Jouke Jan, Hougaard, David M., Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O’Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Dannlowski, Udo, de Geus, E. J.C., Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O’Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Reininghaus, Eva, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schweizer, Barbara W., Severino, Giovanni, Shilling, Paul D., Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Maj, Mario, Turecki, Gustavo, Vieta, Eduard, Veeh, Julia, Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, McMahon, Francis J., APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, APH - Digital Health, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Jamain, Stéphane, University of Adelaide, South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), Mental Health Services [Adelaide, SA, Australia], National Institute of Mental Health (NIMH), Ludwig Maximilian University [Munich] (LMU), Georg-August-University = Georg-August-Universität Göttingen, Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard Medical School [Boston] (HMS), Harvard School of Public Health, University of California [San Diego] (UC San Diego), University of California (UC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Dokkyo Medical University, Università degli Studi di Cagliari = University of Cagliari (UniCa), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain] (CIBERSAM), Hospital Sant Joan de Déu [Barcelona], Geneva University Hospital (HUG), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Karl-Franzens-Universität Graz, Mayo Clinic [Rochester], McGill University Health Center [Montreal] (MUHC), National Taiwan University [Taiwan] (NTU), University Hospital Basel [Basel], Poznan University of Medical Sciences [Poland] (PUMS), Johns Hopkins University (JHU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Basel (Unibas), Neuroscience Research Australia [Sydney, NSW, Australia] (NRA), University of New South Wales [Sydney] (UNSW), Psychiatrie de l'enfant et de l'adolescent [CH C. Perrens, Bordeaux], SECOP - centre hospitalier Charles Perrens, Dalhousie University [Halifax], 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry [Bucharest, Romania], Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], Osaka University [Osaka], Graduate School of Medicine [Osaka], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Psychiatrie et Psychologie Clinique de Liaison [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Psychothérapique de Nancy (CPN), National Institutes of Health [Bethesda] (NIH), Environmental Molecular Biology Laboratory (RIKEN), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Goethe-University Frankfurt am Main, Landesklinikum Neunkirchen (LK Neunkirchen), Hokkaido University Graduate School of Medicine [Sapporo, Japan], Sahlgrenska Academy at University of Gothenburg [Göteborg], Research Service VA San Diego Healthcare System, Università degli Studi di Perugia = University of Perugia (UNIPG), University of Cincinnati (UC), IMIM-Hospital del Mar, Generalitat de Catalunya, Max Planck Institute of Experimental Medicine [Göttingen] (MPI), Max-Planck-Gesellschaft, University of Salerno (UNISA), University of the Study of Campania Luigi Vanvitelli, National Institute of Mental Health [Klecany, Czech Republic] (NIMH), Nagoya University Graduate School of Medicine [Japon], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Medical University Graz, Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Sigmund Freud University (SFU), Douglas Mental Health University Institute [Montréal], University of Heidelberg, Medical Faculty, Black Dog Institute [Sydney, Australia], Johns Hopkins Bloomberg School of Public Health [Baltimore], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, The Florey Institute of Neuroscience and Mental Health [Parkville, VIC, Australie], University of Melbourne, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium: Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till F M Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T F Beekman, Tim B Bigdeli, Elisabeth B Binder, Douglas H R Blackwood, Julien Bryois, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Varregaard Christensen, Toni-Kim Clarke, Jonathan R I Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E Crawford, Gail Davies, Ian J Deary, Franziska Degenhardt, Eske M Derks, Nese Direk, Conor V Dolan, Erin C Dunn, Thalia C Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Héléna A Gaspar, Michael Gill, Fernando S Goes, Scott D Gordon, Jakob Grove, Lynsey S Hall, Christine Søholm Hansen, Thomas F Hansen, Stefan Herms, Ian B Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A Knowles, Isaac S Kohane, Julia Kraft, Warren W Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A Lind, Donald J MacIntyre, Dean F MacKinnon, Robert M Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E Medland, Divya Mehta, Christel M Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M Mondimore, Grant W Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G Nivard, Dale R Nyholt, Paul F O'Reilly, Hogni Oskarsson, Michael J Owen, Jodie N Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E Peterson, Erik Pettersson, Wouter J Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A Quiroz, Per Qvist, John P Rice, Brien P Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C Schulte, Ling Shen, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Grant C B Sinnamon, Johannes H Smit, Daniel J Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A Thomson, Thorgeir E Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M van Hemert, Alexander Viktorin, Peter M Visscher, Yunpeng Wang, Bradley T Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H Witt, Yang Wu, Hualin S Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T Baune, Klaus Berger, Dorret I Boomsma, Sven Cichon, Udo Dannlowski, E J C de Geus, J Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J Grabe, Steven P Hamilton, Caroline Hayward, Andrew C Heath, Kenneth S Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S Li, Susanne Lucae, Pamela A F Madden, Patrik K Magnusson, Nicholas G Martin, Andrew M McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M Nöthen, Michael C O'Donovan, Sara A Paciga, Nancy L Pedersen, Brenda W J H Penninx, Roy H Perlis, David J Porteous, James B Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M Weissman, Thomas Werge, Cathryn M Lewis, Douglas F Levinson, Gerome Breen, Anders D Børglum, Patrick F Sullivan., Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Georg-August-University [Göttingen], University of California, Universita degli Studi di Cagliari [Cagliari], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Graz, Università degli Studi di Perugia (UNIPG), University of Münster, Karl-Franzens-Universität [Graz, Autriche], Amare, A. T., Schubert, K. O., Hou, L., Clark, S. R., Papiol, S., Cearns, M., Heilbronner, U., Degenhardt, F., Tekola-Ayele, F., Hsu, Y. -H., Shekhtman, T., Adli, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Brichant-Petitjean, C., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Del Zompo, M., Depaulo, J. R., Etain, B., Jamain, S., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Herms, S., Hoffmann, P., Hofmann, A., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J. R., Kittel-Schneider, S., Kliwicki, S., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Tortorella, A., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S. L., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Pfennig, A., Potash, J. B., Reif, A., Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., Agerbo, E., Air, T. M., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bigdeli, T. B., Binder, E. B., Blackwood, D. H. R., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J., Clarke, T. -K., Coleman, J. R. I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G. E., Davies, G., Deary, I. J., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Kiadeh, F. F. H., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Gordon, S. D., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Ising, M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Krogh, J., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Mcgrath, P., Mcguffin, P., Medland, S. E., Mehta, D., Middeldorp, C. M., Mihailov, E., Milaneschi, Y., Milani, L., Montgomery, G. W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Owen, M. J., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Pettersson, E., Peyrot, W. J., Pistis, G., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Rivera, M., Mirza, S. S., Schoevers, R., Schulte, E. C., Shen, L., Shi, J., Shyn, S. I., Sigurdsson, E., Sinnamon, G. C. B., Smit, J. H., Smith, D. J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K. E., Teismann, H., Teumer, A., Thompson, W., Thomson, P. A., Thorgeirsson, T. E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A. G., Umbricht, D., Van der Auwera, S., van Hemert, A. M., Viktorin, A., Visscher, P. M., Wang, Y., Webb, B. T., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Witt, S. H., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Baune, B. T., Berger, K., Boomsma, D. I., Dannlowski, U., de Geus, E. J. C., Domenici, E., Domschke, K., Esko, T., Grabe, H. J., Hamilton, S. P., Hayward, C., Heath, A. C., Kendler, K. S., Kloiber, S., Lewis, G., Li, Q. S., Lucae, S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Mortensen, P. B., Muller-Myhsok, B., Nordentoft, M., O'Donovan, M. C., Paciga, S. A., Pedersen, N. L., Penninx, B. W. J. H., Perlis, R. H., Porteous, D. J., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T. G., Smoller, J. W., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M. M., Werge, T., Lewis, C. M., Levinson, D. F., Breen, G., Borglum, A. D., Sullivan, P. F., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Maj, M., Turecki, G., Vieta, E., Veeh, J., Wright, A., Zandi, P. P., Mitchell, P. B., Bauer, M., Alda, M., Mcmahon, F. J., and Adult Psychiatry
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Lithium (medication), [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Genome-wide association study, Logistic regression, THERAPY, ddc:616.89, 0302 clinical medicine, Medicine, Major depression, PREDICTORS, Depression (differential diagnoses), RISK, Depression, Psychiatry and Mental health, Quartile, Cohort, AUGMENTATION, medicine.drug, POLARITY, medicine.medical_specialty, GENETICS, Bipolar disorder, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Lithium, PROPHYLACTIC LITHIUM, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Internal medicine, Humans, ddc:610, AGENTS, Molecular Biology, Genetic association, Depressive Disorder, Major, business.industry, medicine.disease, EFFICACY, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, PHARMACOLOGICAL-TREATMENTS, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
Published: 2021

46. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Author: Michael McCarthy, Claire O'Donovan, Urs Heilbronner, Ichiro Kusumi, Eduard Vieta, Liping Hou, Hsi-Chung Chen, Claire Slaney, Maria Grigoroiu-Serbanescu, Kazufumi Akiyama, Michael Bauer, Janusz K. Rybakowski, Frank Bellivier, Marion Leboyer, Katzutaka Shimoda, Palmiero Monteleone, Cristiana Cruceanu, Alessio Squassina, Stephanie H. Witt, Tadafumi Kato, Giovanni Severino, Alfonso Tortorella, J. Raymond DePaulo, Martin Alda, Louise Frisén, Mazda Adl, Martin Schalling, Per Hoffmann, Susan G. Leckband, Jean-Pierre Kahn, Jean-Michel Aubry, Francis J. McMahon, Sven Cichon, Alexandre Dayer, Tatyana Shekhtman, Franziska Degenhardt, James B. Potash, Bruno Etain, Joseph Frank, Antonio Benabarre, Bernhard T. Baune, Gloria Roberts, Ryota Hashimoto, Tomas Novak, Paul D. Shilling, Julia Veeh, Joanna M. Biernacka, Barbara König, Peter Falkai, Philip B. Mitchell, Urban Ösby, Esther Jiménez, Sébastien Gard, Mark A. Frye, Sarah Kittel-Schneider, Layla Kassem, Fasil Tekola-Ayele, Armin Birner, Cynthia Marie-Claire, Raffaella Ardau, Abesh Kumar Bhattacharjee, Stéphane Jamain, Julie Garnham, Guy A. Rouleau, Caterina Chillotti, Piotr M. Czerski, Thomas G. Schulze, Gustavo Turecki, Anbupalam Thalamuthu, Claudia Pisanu, Azmeraw T. Amare, Marina Mitjans, Sergi Papiol, Mario Maj, Bárbara Arias, Janice M. Fullerton, Nina Dalkner, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Klaus Oliver Schubert, Francis M. Mondimore, Eva Z. Reininghaus, Fernando S. Goes, Lena Backlund, Francesc Colom, Catharina Lavebratt, Christian Simhandl, Marcella Rietschel, Micah Cearns, Mikael Landén, Norio Ozaki, Gonzalo Laje, Barbara W. Schweizer, Nirmala Akula, Andrea Pfennig, Yi-Hsiang Hsu, John R. Kelsoe, Lina Martinsson, Markus M. Nöthen, Caroline M. Nievergelt, Pavla Stopkova, Mirko Manchia, Susan L. McElroy, Peter P. Zandi, Scott R. Clark, Joanna Hauser, Andreas J. Forstner, Po-Hsiu Kuo, Andreas Reif, Maria Del Zompo, Paul Grof, Fabian Streit, Ewa Ferensztajn-Rochowiak, Pablo Cervantes, Thomas Stamm, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Digital Health, Schubert, K. O., Thalamuthu, A., Amare, A. T., Frank, J., Streit, F., Adl, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Marie-Claire, C., Cearns, M., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Clark, S. R., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Etain, B., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Heilbronner, U., Herms, S., Hoffmann, P., Hou, L., Hsu, Y. -H., Jamain, S., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J., Kittel-Schneider, S., Ferensztajn-Rochowiak, E., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Maj, M., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Papiol, S., Pfennig, A., Pisanu, C., Potash, J. B., Reif, A., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shekhtman, T., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Tekola-Ayele, F., Tortorella, A., Turecki, G., Veeh, J., Vieta, E., Witt, S. H., Roberts, G., Zandi, P. P., Alda, M., Bauer, M., Mcmahon, F. J., Mitchell, P. B., Schulze, T. G., Rietschel, M., and Baune, B. T.
Subjects: Oncology, Multifactorial Inheritance, Treatment response, medicine.medical_specialty, Lithium (medication), Bipolar disorder, Poor responder, Neurosciences. Biological psychiatry. Neuropsychiatry, Lithium, DISEASE, Article, Cellular and Molecular Neuroscience, Risk Factors, Internal medicine, medicine, Humans, Manic-depressive illness, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Depressió psíquica, METAANALYSIS, Biological Psychiatry, Depression (differential diagnoses), MANIA, Depressive Disorder, Depressive Disorder, Major, Trastorn bipolar, Depression, business.industry, Major, medicine.disease, Pathway analysis, Liti, COMPARATIVE EFFICACY, Psychiatry and Mental health, Mental depression, Schizophrenia, Polygenic risk score, Esquizofrènia, Pharmacogenomics, business, RC321-571, medicine.drug
Abstract: Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
Published: 2021

47. Photoluminescence properties and characterization of LiF-based imaging detector irradiated by 10 keV XFEL beam

Author: Toshinori Yabuuchi, Massimo Piccinini, S. S. Makarov, Daisuke Sagae, Takeshi Matsuoka, R. M. Montereali, S. A. Pikuz, Makina Yabashi, Tatiana Pikuz, Enrico Nichelatti, M. Koenig, Maria Aurora Vincenti, Norimasa Ozaki, Francesca Bonfigli, Yuichi Inubushi, Nickolas Hartley, Juha, Libor, Bonfigli, F., Hartley, N. J., Inubushi, Y., Koenig, M., Matsuoka, T., Makarov, S., Montereali, R. M., Nichelatti, E., Ozaki, N., Piccinini, M., Pikuz, S., Pikuz, T., Sagae, D., Vincenti, M. A., Yabashi, M., and Yabuuchi, T.
Subjects: Materials science, Photoluminescence, Physics::Optics, Photoluminescent color centers, law.invention, SACLA, chemistry.chemical_compound, Photoluminescent color center, Optics, Optical microscope, law, Physics::Atomic and Molecular Clusters, Irradiation, Hard X-ray FEL, LiF imaging detectors, Pump-probe experiment, X-ray radiography, business.industry, Free-electron laser, Lithium fluoride, Pulse duration, LiF imaging detector, chemistry, Physics::Accelerator Physics, business, Beam (structure)
Abstract: We present the study of optical and spectral properties of radiation-induced stable point defects, known as color centers (CCs), in lithium fluoride (LiF) for the detection of 10 keV XFEL beam at Spring-8 Angstrom Compact free electron LAser (SACLA) in Japan. A thick LiF crystal was irradiated in four spots with 10 keV XFEL beam (pulse duration = 10 fs) with different number of accumulated shots. After irradiation the colored-LiF spots were characterized with an optical microscope in fluorescence mode and their photoluminescence intensity and spectra were analyzed.
Published: 2019

48. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

Author: J. Raymond DePaulo, Martin Alda, Alfonso Tortorella, Susan G. Leckband, Jean-Michel Aubry, James B. Potash, Clara Brichant-Petitjean, Layla Kassem, Joanna Hauser, Tomas Novak, David Zilles, Claire O'Donovan, Rebecca Hoban, Sarah Kittel-Schneider, Claire Slaney, Lena Backlund, Peter Falkai, Andrew T. A. Cheng, John R. Kelsoe, Andrea Pfennig, Janice M. Fullerton, Marcella Rietschel, Caterina Chillotti, Stéphane Jamain, Elise Bui, Po-Hsiu Kuo, Alessio Squassina, Claudio E. M. Banzato, Joanna M. Biernacka, Lisa R. Seymour, Naomi R. Wray, Ichiro Kusumi, Thomas Stamm, Fernando S. Goes, Audrey Nallet, Sarah K. Tighe, Giovanni Severino, Jean-Pierre Kahn, Maria Neuner, Nirmala Akula, Norio Ozaki, Francis J. McMahon, Frank Bellivier, Andreas Reif, Ryota Hashimoto, Barbara W. Schweizer, Palmiero Monteleone, Florian Seemüller, Urs Heilbronner, Sevilla D. Detera-Wadleigh, Pavla Stopkova, Martin Schalling, Julie Garnham, Sébastien Gard, Mark A. Frye, Eva Z. Reininghaus, Lina Martinsson, Urban Ösby, Maria Grigoroiu-Serbanescu, Sara Richardson, Tadafumi Kato, Marion Leboyer, Catharina Lavebratt, Piotr M. Czerski, Scott R. Clark, Daniela Reich-Erkelenz, Sebastian Kliwicki, Guy A. Rouleau, Oliver Gruber, Gonzalo Laje, Adam Wright, Gustavo Turecki, Roy H. Perlis, Takuya Masui, Mirko Manchia, Bernhard T. Baune, Mazda Adli, Michael Bauer, Sven Cichon, Frank Mondimore, Bruno Etain, Philip B. Mitchell, Thomas G. Schulze, Peter P. Zandi, Raffaella Ardau, Peter R. Schofield, Susanne Bengesser, Liping Hou, Janusz K. Rybakowski, Mario Maj, Clarissa de Rosalmeida Dantas, Louise Frisén, O. Schubert, Carlos Jaramillo, Maria Del Zompo, Paul Grof, Cynthia V. Calkin, Jo Steele, Jordan W. Smoller, Alain Malafosse, Manchia, M, Adli, M, Akula, N, Ardau, R, Aubry, Jm, Backlund, L, Banzato, Ce, Baune, Bt, Bellivier, F, Bengesser, S, Biernacka, Jm, Brichant Petitjean, C, Bui, E, Calkin, Cv, Cheng, At, Chillotti, C, Cichon, S, Clark, S, Czerski, Pm, Dantas, C, Zompo, Md, Depaulo, Jr, Detera Wadleigh, Sd, Etain, B, Falkai, P, Frisén, L, Frye, Ma, Fullerton, J, Gard, S, Garnham, J, Goes, F, Grof, P, Gruber, O, Hashimoto, R, Hauser, J, Heilbronner, U, Hoban, R, Hou, L, Jamain, S, Kahn, Jp, Kassem, L, Kato, T, Kelsoe, Jr, Kittel Schneider, S, Kliwicki, S, Kuo, Ph, Kusumi, I, Laje, G, Lavebratt, C, Leboyer, M, Leckband, Sg, López Jaramillo, Ca, Maj, Mario, Malafosse, A, Martinsson, L, Masui, T, Mitchell, Pb, Mondimore, F, Monteleone, P, Nallet, A, Neuner, M, Novák, T, O'Donovan, C, Osby, U, Ozaki, N, Perlis, Rh, Pfennig, A, Potash, Jb, Reich Erkelenz, D, Reif, A, Reininghaus, E, Richardson, S, Rouleau, Ga, Rybakowski, Jk, Schalling, M, Schofield, Pr, Schubert, Ok, Schweizer, B, Seemüller, F, Grigoroiu Serbanescu, M, Severino, G, Seymour, Lr, Slaney, C, Smoller, Jw, Squassina, A, Stamm, T, Steele, J, Stopkova, P, Tighe, Sk, Tortorella, Alfonso Antonio Vincenzo, Turecki, G, Wray, Nr, Wright, A, Zandi, Pp, Zilles, D, Bauer, M, Rietschel, M, Mcmahon, Fj, Schulze, Tg, Alda, M., Department of Psychiatry, Dalhousie University [Halifax], Department of Psychiatry and Psychotherapy, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Unit of Clinical Pharmacology, University-Hospital of Cagliari, Department of Mental Health and Psychiatry, University Hospital of Geneva, Trinity College Dublin-St. James's Hospital, University of Campinas [Campinas] (UNICAMP), University of Adelaide, Pôle de Psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Medical University Graz, Mayo Clinic, Division of Epidemiology and Genetics, Academia Sinica-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo (USP)-Universidade de São Paulo (USP), Department of Genomics, Life and Brain Center, University of Bonn, Psychiatric Genetic Unit, Poznan University of Medical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, University of Homburg, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Service de psychiatrie adulte, Université Bordeaux Segalen - Bordeaux 2-Hôpital Charles Perrens-Centre Expert Trouble Bipolaire, Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], University of Toronto, Georg-August-University [Göttingen], Osaka University Graduate School of Medicine, University of California [San Diego] (UC San Diego), University of California-University of California, Service de Psychiatrie et Psychologie Clinique, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital Jeanne-d'Arc, Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Center for Brain Science [Wako] (RIKEN CBS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Mental Health Sciences Unit, University College of London [London] (UCL), Department of Adult Psychiatry, Institute of Epidemiology and Preventive Medicine, National Taiwan University [Taiwan] (NTU), Hokkaido University Graduate School of Medicine, Molecular Medicine and Surgery department, Karolinska Institutet [Stockholm], Center for Molecular Medicine, Karolinska University Hospital [Stockholm], Department of Pharmacy, Veterans Affairs San Diego Healthcare System, Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego], University of Antioquia, University of Napoli, School of Psychiatry, University of New South Wales [Sydney] (UNSW)-Black Dog Institute, Prague Psychiatric Center, University of Prague, Fujita Health University School of Medicine, Nagoya University Graduate School of Medicine, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Iowa [Iowa City], Center of Excellence in Neuroscience, CHU de Montréal, Department of Medicine, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Psychiatric Hospital, McGill Group for Suicide Studies, Douglas Mental Health University Institute, Queensland Brain Institute, University of Queensland [Brisbane], Department of Mental Health, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, The work on assessment of lithium response has been supported by a grant from Canadian Institutes of Health Research #64410 to MA. MG-S was supported by Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI), Bucharest, Romania (grant no. 89/2012). JMA and AN were supported by a grant from the Swiss National Foundation (#32003B_125469/1 to JM Aubry). ConLiGen is in part supported by funds from the Intramural Research Program of the National Institute of Mental Health (NIMH) at the National Institutes of Health (NIH), Department of Health and Human Services, United States Government, Aubry, Jean-Michel, Universidade Estadual de Campinas = University of Campinas (UNICAMP), Universidade de São Paulo = University of São Paulo (USP)-Universidade de São Paulo = University of São Paulo (USP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Georg-August-University = Georg-August-Universität Göttingen, University of California (UC)-University of California (UC), Guellaen, Georges, Université Bordeaux Segalen - Bordeaux 2-Centre hospitalier Charles Perrens [Bordeaux]-Centre Expert Trouble Bipolaire, and Ikeda, Kazutaka
Subjects: Male, Bipolar Disorder, Lithium (medication), Psychometrics, Psychopharmacology, Epidemiology, International Cooperation, lcsh:Medicine, Lithium, Maintenance Treatment, ConLiGen, ddc:616.89, 0302 clinical medicine, Antimanic Agents, Psychology, lcsh:Science, Reliability (statistics), Psychiatry, Genetics, 0303 health sciences, Multidisciplinary, ASSOCIATION, Genomics, Pharmacoepidemiology, 3. Good health, Mental Health, Phenotype, Treatment Outcome, MAPPING SUSCEPTIBILITY GENES, Behavioral Pharmacology, RELIABILITY, Lithium Compounds, Medicine, Female, Research Article, medicine.drug, Drugs and Devices, MAPPING SUSCEPTIBILITY GENES, PROPHYLACTIC LITHIUM, OBSERVER AGREEMENT, MOOD DISORDERS, ONSET, ASSOCIATION, RELIABILITY, MORTALITY, ILLNESS, AGE, ILLNESS, PROPHYLACTIC LITHIUM, 03 medical and health sciences, AGE, Neuropharmacology, Genomic Medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genome-Wide Association Studies, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Bipolar disorder, ddc:610, Biology, 030304 developmental biology, Mood Disorders, business.industry, MORTALITY, lcsh:R, Computational Biology, Reproducibility of Results, Models, Theoretical, medicine.disease, OBSERVER AGREEMENT, Mood disorders, Pharmacogenetics, Therapies, ONSET, lcsh:Q, Pharmacogenomics, business, 030217 neurology & neurosurgery, Kappa
Abstract: Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa ($\kappa$)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes ($\kappa$ = 0.66 and $\kappa$ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages ($ICC_1 = 0.71$ and $ICC_2 = 0.75$, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
Published: 2013

49. The CLOCK gene and mood disorders: a case-control study and meta-analysis

Author: Christoph U. Correll, Taro Kishi, Yasuhisa Fukuo, Hiroshi Ujike, Shinji Matsunaga, Takeo Yoshikawa, Wakako Umene-Nakano, Reiji Yoshimura, Nakao Iwata, Hiroshi Kunugi, Alessandro Serretti, Tomo Okochi, Toshiya Inada, Jun Nakamura, Tadafumi Kato, Norio Ozaki, Tsuyoshi Kitajima, Kishi T., Yoshimura R., Fukuo Y., Kitajima T., Okochi T., Matsunaga S., Inada T., Kunugi H., Kato T., Yoshikawa T., Ujike H., Umene-Nakano W., Nakamura J., Ozaki N., Serretti A., Correll C.U., and Iwata N.
Subjects: Adult, Male, Candidate gene, MOOD DISORDERS, Physiology, CLOCK, CLOCK Proteins, Single-nucleotide polymorphism, Bioinformatics, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Asian People, Japan, Physiology (medical), mental disorders, medicine, Humans, Bipolar disorder, RNA, Messenger, Genetic Association Studies, Aged, Genetics, MAJOR DEPRESSIVE DISORDER, Depressive Disorder, Major, BIPOLAR DISORDER, tagging SNP, Middle Aged, medicine.disease, Mood, Mood disorders, Case-Control Studies, Major depressive disorder, Female, CIRCADIAN RHYTHMS, Psychology
Abstract: The clock gene (CLOCK) is considered to be a good candidate gene for the pathophysiology of mood disorders, including bipolar disorder (BP) and major depressive disorder (MDD). rs1801260 (T3111C) has been detected at position 3111 in the CLOCK mRNA 3' untranslated region, and was reported to be associated with a substantial delay in preferred timing for activity and sleep in a human study. As for function, rs1801260 has been speculated to affect mRNA. Therefore, the authors investigated the association between the three tagging single-nucleotide polymorphisms (SNPs) (rs3736544, rs1801260, and rs3749474) in CLOCK and risk of BP (n=867) and MDD (n=139) compared to controls (n=889) in the Japanese population. In addition, we also performed an updated meta-analysis of nine published, genetic association studies investigating the relationship between rs1801260 and mood disorder risk, comprising 3321 mood disorders cases and 3574 controls. We did not detect any associations between tagging SNPs in CLOCK and BP or MDD in the allele, genotype, or haplotype analysis (global p(BP)=.605 and global p(MDD)=.211). Moreover, rs1801260 was also not associated with BP, MDD, or any mood disorders in the meta-analysis. In conclusion, these data suggest that CLOCK does not play a major role in the pathophysiology of mood disorders.
Published: 2011

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