High harmonic generation by short laser pulses: time-frequency behavior and applications to attophysics

High harmonic generation (HHG) is a process in which noble gas atoms excited by an intense laser field at frequency ω1 emit radiation of higher frequencies that are odd integer multiples of ω1. Driven by an infrared laser, high harmonic radiation can span from the optical into the extreme ultraviolet (XUV) frequency range. In this thesis, I study HHG using short laser pulses by solving the time-dependent Schrödinger equation (TDSE). In particular, I will focus on calculating and controlling the time-dependent instantaneous frequency (chirp) of high harmonics. The harmonic chirp is a direct consequence of the atom-field interaction during HHG, and its behavior in the time-frequency domain reveals the fundamental physics in the strong laser field. In addition, controlling the harmonic chirp is essential for practical applications such as when high harmonic radiation is used as a seed for soft X-ray lasers. Moreover, I will discuss how to find the ionization probability of an atom exposed to few-cycle laser pulses. This is important in order to understand the propagation effects on high harmonics as their driving pulse goes through a rapidly ionizing medium. Finally, I will consider high harmonics as a source of attosecond pulses. Such short pulses (∼10-18 seconds) could induce and probe the dynamics of electrons in atoms and solids. In the last part of my thesis, I will examine some examples of attosecond electron dynamics

Spatial separation of large dynamical blue shift and harmonic generation

We study the temporal and spatial dynamics of the large amplitude and frequency modulation that can be induced in an intense, few cycle laser pulse as it propagates through a rapidly ionizing gas. Our calculations include both single atom and macroscopic interactions between the non-linear medium and the laser field. We analyze the harmonic generation by such pulses and show that it is spatially separated from the ionization dynamics which produce a large dynamical blue shift of the laser pulse. This means that small changes in the initial laser focusing conditions can lead to large differences in the laser frequency modulation, even though the generated harmonic spectrum remains essentially unchanged.Comment: 4 pages, 5 figures. Under revisio

Loss of Parp-1 affects gene expression profile in a genome-wide manner in ES cells and liver cells

BACKGROUND: Many lines of evidence suggest that poly(ADP-ribose) polymerase-1 (Parp-1) is involved in transcriptional regulation of various genes as a coactivator or a corepressor by modulating chromatin structure. However, the impact of Parp-1-deficiency on the regulation of genome-wide gene expression has not been fully studied yet. RESULTS: We employed a microarray analysis covering 12,488 genes and ESTs using mouse Parp-1-deficient (Parp-1(-/-)) embryonic stem (ES) cell lines and the livers of Parp-1(-/- )mice and their wild-type (Parp-1(+/+)) counterparts. Here, we demonstrate that of the 9,907 genes analyzed, in Parp-1(-/- )ES cells, 9.6% showed altered gene expression. Of these, 6.3% and 3.3% of the genes were down- or up-regulated by 2-fold or greater, respectively, compared with Parp-1(+/+ )ES cells (p < 0.05). In the livers of Parp-1(-/- )mice, of the 12,353 genes that were analyzed, 2.0% or 1.3% were down- and up-regulated, respectively (p < 0.05). Notably, the number of down-regulated genes was higher in both ES cells and livers, than that of the up-regulated genes. The genes that showed altered expression in ES cells or in the livers are ascribed to various cellular processes, including metabolism, signal transduction, cell cycle control and transcription. We also observed expression of the genes involved in the pathway of extraembryonic tissue development is augmented in Parp-1(-/- )ES cells, including H19. After withdrawal of leukemia inhibitory factor, expression of H19 as well as other trophoblast marker genes were further up-regulated in Parp-1(-/- )ES cells compared to Parp-1(+/+ )ES cells. CONCLUSION: These results suggest that Parp-1 is required to maintain transcriptional regulation of a wide variety of genes on a genome-wide scale. The gene expression profiles in Parp-1-deficient cells may be useful to delineate the functional role of Parp-1 in epigenetic regulation of the genomes involved in various biological phenomena

Giantin Affects Golgi Stack Connection

Golgins are a family of Golgi-localized long coiled-coil proteins. The major golgin function is thought to be the tethering of vesicles, membranes, and cytoskeletal elements to the Golgi. We previously showed that knockdown of one of the longest golgins, Giantin, altered the glycosylation patterns of cell surfaces and the kinetics of cargo transport, suggesting that Giantin maintains correct glycosylation through slowing down transport within the Golgi. Giantin knockdown also altered the sizes and numbers of mini Golgi stacks generated by microtubule de-polymerization, suggesting that it maintains the independence of individual Golgi stacks. Therefore, it is presumed that Golgi stacks lose their independence following Giantin knockdown, allowing easier and possibly increased transport among stacks and abnormal glycosylation. To gain structural insights into the independence of Golgi stacks, we herein performed electron tomography and 3D modeling of Golgi stacks in Giantin knockdown cells. Compared with control cells, Giantin-knockdown cells had fewer and smaller fenestrae within each cisterna. This was supported by data showing that the diffusion rate of Golgi membrane proteins is faster in Giantin-knockdown Golgi, indicating that Giantin knockdown structurally and functionally increases connectivity among Golgi cisternae and stacks. This increased connectivity suggests that contrary to the cis-golgin tether model, Giantin instead inhibits the tether and fusion of nearby Golgi cisternae and stacks, resulting in transport difficulties between stacks that may enable the correct glycosylation of proteins and lipids passing through the Golgi

The Golgin Protein Giantin Regulates Interconnections Between Golgi Stacks

Golgins are a family of Golgi-localized long coiled-coil proteins. The major golgin function is thought to be the tethering of vesicles, membranes, and cytoskeletal elements to the Golgi. We previously showed that knockdown of one of the longest golgins, Giantin, altered the glycosylation patterns of cell surfaces and the kinetics of cargo transport, suggesting that Giantin maintains correct glycosylation through slowing down transport within the Golgi. Giantin knockdown also altered the sizes and numbers of mini Golgi stacks generated by microtubule de-polymerization, suggesting that it maintains the independence of individual Golgi stacks. Therefore, it is presumed that Golgi stacks lose their independence following Giantin knockdown, allowing easier and possibly increased transport among stacks and abnormal glycosylation. To gain structural insights into the independence of Golgi stacks, we herein performed electron tomography and 3D modeling of Golgi stacks in Giantin knockdown cells. Compared with control cells, Giantin-knockdown cells had fewer and smaller fenestrae within each cisterna. This was supported by data showing that the diffusion rate of Golgi membrane proteins is faster in Giantin-knockdown Golgi, indicating that Giantin knockdown structurally and functionally increases connectivity among Golgi cisternae and stacks. This increased connectivity suggests that contrary to the cis-golgin tether model, Giantin instead inhibits the tether and fusion of nearby Golgi cisternae and stacks, resulting in transport difficulties between stacks that may enable the correct glycosylation of proteins and lipids passing through the Golgi

Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is a non-invasive therapeutic technique for treating malignant tumors, however, methods to evaluate its therapeutic efficacy and adverse reactions are lacking. High mobility group box 1 (HMGB1) is an inflammatory molecule released during cell death. Therefore, we aimed to investigate HMGB1 as a biomarker for BNCT response, by examining the early responses of tumor cells to 10B-boronophenylalanine (BPA)-based BNCT in the Kyoto University Nuclear Reactor. Extracellular HMGB1 release was significantly increased in human squamous carcinoma SAS and melanoma A375 cells 24 h after neutron irradiation but not after γ-irradiation. At 3 days post-BPA-based BNCT irradiation in a SAS xenograft mouse model, plasma HMGB1 levels were higher than those in the non-irradiation control, and HMGB1 was detected in both nuclei and cytoplasm in tumor cells. Additionally, increased plasma HMGB1 levels post-BNCT irradiation were detected even when tumors decreased in size. Collectively, these results indicate that the extracellular HMGB1 release occurs at an early stage and is persistent when tumors are reduced in size; therefore, it is a potential biomarker for evaluating the therapeutic response during BNCT

異教科で協働できる教員を育成するための実践的研究（1） : 教科教育学専攻の共通科目の始動を通じて

本研究は，平成28 年度より始まった「教科教育学専攻」における新しい共通科目（「教科教育学研究方法論」，「教科教育学融合プロジェクト」，「教科教育学の実践的展開」，「教科教育学の実践的検証」）が始動する際に得られた知見を分析・考察し報告するもので，その全容は平成29 年３月に公開予定のホームページで公表される。本報告書は，その研究の要旨を，(1)　経緯について，(2)　各教科について，(3)　実践からの考察，(4)　理論からの考察，(5)　学生の振り返りからの考察の五点から述べる