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Age at exposure is a major modifier of radiation-induced carcinogenesis. We used mouse models to elucidate the mechanism underlying age-related susceptibility to radiation-induced tumorigenesis. Radiation exposure in infants was effective at inducing tumors in B6/B6-Chr18MSM-F1 ApcMin/+ mice. Loss of heterozygosity analysis revealed that interstitial deletion may be considered a radiation signature in this model and tumor number containing a deletion correlated with the susceptibility to radiation-induced tumorigenesis as a function of age. Furthermore, in Lgr5-eGFP-ires-CreERT2; Apcflox/flox mice, deletions of both floxed Apc alleles in Lgr5-positive stem cells in infants resulted in the formation of more tumors than in adults. These results suggest that tumorigenicity of Apc-deficient stem cells varies with age and is higher in infant mice. Three-dimensional immunostaining analyses indicated that the crypt architecture in the intestine of infants was immature and different from that in adults concerning crypt size and the number of stem cells and Paneth cells per crypt. Interestingly, the frequency of crypt fission correlated with the susceptibility to radiation-induced tumorigenesis as a function of age. During crypt fission, the percentage of crypts with lysozyme-positive mature Paneth cells was lower in infants than that in adults, whereas no difference in the behavior of stem cells or Paneth cells was observed regardless of age. These data suggest that morphological dynamics in intestinal crypts affect age-dependent susceptibility to radiation-induced tumorigenesis; oncogenic mutations in infant stem cells resulting from radiation exposure may acquire an increased proliferative potential for tumor induction compared with that in adults.

In living organisms, sensitivity to radiation increases in the presence of oxygen (OOInduction of DNA damage (marker: γ-H2A histone family member X) and mitochondrial signaling (AMP-activated protein kinase), suppression of mitochondrial metabolic activity, and generation of reactive oxygen species occurred with radiation in cells cultured under 5% and 20% OO

S1. The percentage of TIG-3 and MRC-5 cells with alpha-SMA staining exposed to indicated doses is shown in the graph. S2. Tumor volumes of HeLa, HeLa+MRC-5 0FR tumors, HeLa+MRC-5 0.05FR tumors, HeLa+MRC-5 NAC 0FR tumors, and HeLa+MRC-5 0.05FR tumors.

Fibroblasts are a key stromal cell in the tumor microenvironment (TME) and promote tumor growth via release of various growth factors. Stromal fibroblasts in cancer, called cancer-associated fibroblasts (CAF), are related to myofibroblasts, an activated form of fibroblast. While investigating the role of stroma fibroblasts on radiation-related carcinogenesis, it was observed following long-term fractionated radiation (FR) that the morphology of human diploid fibroblasts changed from smaller spindle shapes to larger flat shapes. These cells expressed smooth muscle actin (α-SMA) and platelet-derived growth factor receptors, markers of myofibroblasts and CAFs, respectively. Long-term FR induces progressive damage to the fibroblast nucleus and mitochondria via increases in mitochondrial reactive oxygen species (ROS) levels. Here, it is demonstrated that long-term FR-induced α-SMA–positive cells have decreased mitochondrial membrane potential and activated oxidative stress responses. Antioxidant N-acetyl cysteine suppressed radiation-induced mitochondrial damage and generation of myofibroblasts. These results indicate that mitochondrial ROS are associated with the acquisition of myofibroblasts after long-term FR. Mechanistically, mitochondrial ROS activated TGFβ signaling which in turn mediated the expression of α-SMA in radiation-induced myofibroblasts. Finally, in vivo tumor growth analysis in a human tumor xenograft model system revealed that long-term FR-induced myofibroblasts promote tumor growth by enhancing angiogenesis.Implications: Radiation affects malignant cancer cells directly and indirectly via molecular alterations in stromal fibroblasts such as activation of TGFβ and angiogenic signaling pathways. Mol Cancer Res; 16(11); 1676–86. ©2018 AACR.

Induction of alpha-SMA after acute single radiation

Individual tumor measurements data

Supplementary Table 1 from Nonclassic Functions of Human Topoisomerase I: Genome-Wide and Pharmacologic Analyses

The biological functions of nuclear topoisomerase I (Top1) have been difficult to study because knocking out TOP1 is lethal in metazoans. To reveal the functions of human Top1, we have generated stable Top1 small interfering RNA (siRNA) cell lines from colon and breast carcinomas (HCT116-siTop1 and MCF-7-siTop1, respectively). In those clones, Top1 is reduced ∼5-fold and Top2α compensates for Top1 deficiency. A prominent feature of the siTop1 cells is genomic instability, with chromosomal aberrations and histone γ-H2AX foci associated with replication defects. siTop1 cells also show rDNA and nucleolar alterations and increased nuclear volume. Genome-wide transcription profiling revealed 55 genes with consistent changes in siTop1 cells. Among them, asparagine synthetase (ASNS) expression was reduced in siTop1 cells and in cells with transient Top1 down-regulation. Conversely, Top1 complementation increased ASNS, indicating a causal link between Top1 and ASNS expression. Correspondingly, pharmacologic profiling showed l-asparaginase hypersensitivity in the siTop1 cells. Resistance to camptothecin, indenoisoquinoline, aphidicolin, hydroxyurea, and staurosporine and hypersensitivity to etoposide and actinomycin D show that Top1, in addition to being the target of camptothecins, also regulates DNA replication, rDNA stability, and apoptosis. Overall, our studies show the pleiotropic nature of human Top1 activities. In addition to its classic DNA nicking-closing functions, Top1 plays critical nonclassic roles in genomic stability, gene-specific transcription, and response to various anticancer agents. The reported cell lines and approaches described in this article provide new tools to perform detailed functional analyses related to Top1 function. [Cancer Res 2007;67(18):8752–61]

Mathematical simulations of the p53-Mdm2 feedback loop suggest that both proteins will exhibit impulsive expression characteristics in response to high cellular stress levels. However, little quantitative experimental evaluation has been done, particularly of the phosphorylated forms. To evaluate the mathematical models experimentally, we used lysate microarrays from an isogenic pair of γ-ray–irradiated cell lysates from HCT116 (p53+/+ and p53−/−). Both p53 and Mdm2 proteins showed expected pulses in the wild type, whereas no pulses were seen in the knockout. Based on experimental observations, we determined model parameters and generated an in silico “knockout,” reflecting the experimental data, including phosphorylated proteins. [Cancer Res 2007;67(13):6247–52]

Supplementary Methods from Quantitative Assessment of the p53-Mdm2 Feedback Loop Using Protein Lysate Microarrays

Shaping the emission pattern of second harmonic (SH) generation from plasmonic nanoparticles is important for practical applications in nonlinear nanophotonics but is rendered challenging by the complex second-order nonlinear-optical processes. Here, we theoretically and experimentally demonstrate that a pair of V- and Y-shaped gold nanoparticles directs the SH emission perpendicularly to an incident light direction. Owing to spatial overlap of two orthogonal plasmonic dipole modes at the fundamental and SH wavelengths of the individual particles, surface SH polarizations induced by the fundamental field is efficiently near-field coupled to the SH plasmon mode, resulting in dipolar SH emission from the individual particles. Moreover, the phase of this emission can be tuned simply by altering the part of the Y-particle shape, which changes the SH plasmon resonance while keeping the fundamental resonance. Our approach is a promising platform for engineering not only directional nonlinear nanoantennas but also nonlinear metamaterials.

Mitochondria are responsible for controlling cell death during the early stages of radiation exposure, but their perturbations are associated with late effects of radiation-related carcinogenesis. Therefore, it is important to protect mitochondria to mitigate the harmful effects of radiation throughout life. The glutathione peroxidase (GPx) enzyme is essential for the maintenance of mitochondrial-derived reactive oxygen species (ROS) levels. However, radiation inactivates the GPx, resulting in metabolic oxidative stress and prolonged cell injury in irradiated normal human fibroblasts. Here, we used the GPx activator N-acetyl-5-methoxy-tryptamine (melatonin) and a mitochondria-targeted mimic of GPx MitoEbselen-2 to stimulate the GPx. A commercial GPx activity assay kit was used to measure the GPx activity. ROS levels were determined by using some ROS indicators. Protein expression associated with the response of mitochondria to radiation was assessed using immunostaining. Concurrent pre-administration or post-administration of melatonin or MitoEbselen-2 with radiation maintained GPx activity and ROS levels and suppressed mitochondrial radiation responses associated with cellular damage and radiation-related carcinogenesis. In conclusion, melatonin and MitoEbselen-2 prevented radiation-induced mitochondrial injury and metabolic oxidative stress by targeting mitochondria. These drugs have the potential to protect against acute radiation injury and late effects of carcinogenesis in a variety of radiation scenarios assuming pre-administration or post-administration.

The health risks associated with low-dose radiation, which are a major concern after the Fukushima Daiichi nuclear power plant accident (the Fukushima accident), have been extensively investigated, and the cancer risks from low-dose radiation exposure (below ~ 100 mSv) are thought to be negligible. According to World Health Organization and the United Nations Scientific Committee on the Effects of Atomic Radiation reports, the level of radiation exposure from the Fukushima accident is limited, estimating no significant increased risk from the accident. Radiation-induced cell injury is mainly caused by oxidative damage to biomolecules, including DNA, lipids and proteins. Radiation stimulates metabolic activation within the mitochondria to provide energy for the DNA damage response. Mitochondrial respiratory chain complexes I and III are the most important intracellular source of reactive oxygen species (ROS) during oxidative phosphorylation in eukaryotic cells. Manganese superoxide dismutase and glutathione are key players in redox control within cells. However, perturbation of the antioxidant response leads to chronic oxidative stress in irradiated cells. Excess ROS of mitochondrial origin is reported in cancer-associated fibroblast and promotes carcinogenesis. The aim of this review paper is to discuss critical roles of mitochondria in radiation-related cancer by introducing our recent studies. In particular, elevated mitochondrial ROS in stromal fibroblasts potentiate transforming growth factor-beta (TGF-β) signaling, which triggers smooth muscle actin (α-SMA) expression to stimulate myofibroblast differentiation. Radiation-induced myofibroblasts promote tumor growth by enhancing angiogenesis. Thus, radiation affects both malignant cancer cells and neighboring stromal cells through secretion of soluble factors.

We recently made an important discovery that radiation induces myofibroblasts, which play a role in radiation-related carcinogenesis via tumor microenvironment formation. Here, we investigated the threshold dose and the mechanisms of myofibroblast induction to assess adverse radiation effects on normal cells. Single-dose of healthy human fibroblasts in vitro promotes myofibroblast induction at high doses (≥ 5 Gy). In contrast, repeated low dose of fractionated radiation is at least equivalent to high-dose single radiation regarding myofibroblast induction. ROS play a pivotal role in the process of myofibroblast induction in normal tissue injury. Antioxidants, such as epicatechin and ascorbic acid can prevent myofibroblast induction by scavenging ROS. We further investigated the role of DNA damage responses (DDR) on myofibroblast induction. Blocking the DDR using DNA-PK or AKT inhibitors enhanced cellular sensitivity to radiation and facilitated myofibroblast induction, whereas an ATM inhibitor also enhanced radiation sensitivity but abrogated ROS accumulation and myofibroblast induction. In contrast to standard culture conditions, myofibroblasts remained after low or moderate doses of radiation (below 2.5 Gy) under growth-restricted conditions. In conclusion, the recovery of damaged cells from radiation is essential for myofibroblast clearance, which restores stromal cell dormancy and prevents tumor microenvironment formation. However, residual ROS, by way of sustaining myofibroblast presence, can facilitate tumor microenvironment formation. Targeting ROS using antioxidants is effective in the mitigation of radiation-related adverse effects, such as growth retardation and myofibroblast induction, and helps protect normal tissues.

In this paper, we proposed a simple complex amplitude modulated holographic data storage（HDS）system and retrieved both the amplitude and phase data by deep learning from a single-shot intensity image. The complex amplitude of signal beam is modulated by a single spatial light modulator (SLM) based on double phase hologram method, and one object intensity image is captured by the detector. Two convolutional neural networks (CNN) are used to build the relationships between the captured intensity and complex amplitude data pages, respectively. After training the neural networks, both the amplitude and phase information can be directly decoded from one intensity image.

Under physiological and stress conditions, mitochondria act as a signaling platform to initiate biological events, establishing communication from the mitochondria to the rest of the cell. Mitochondrial adenosine triphosphate (ATP), reactive oxygen species, cytochrome C, and damage-associated molecular patterns act as messengers in metabolism, oxidative stress response, bystander response, apoptosis, cellular senescence, and inflammation response. In this review paper, the mitochondrial signaling in response to DNA damage was summarized. Mitochondrial clearance via fusion, fission, and mitophagy regulates mitochondrial quality control under oxidative stress conditions. On the other hand, damaged mitochondria release their contents into the cytoplasm and then mediate various signaling pathways. The role of mitochondrial dysfunction in radiation carcinogenesis was discussed, and the recent findings on radiation-induced mitochondrial signaling and radioprotective agents that targeted mitochondria were presented. The analysis of the mitochondrial radiation effect, as hypothesized, is critical in assessing radiation risks to human health.

In tumor tissues, activated stromal fibroblasts, termed cancer-associated fibroblasts (CAFs), exhibit similar characteristics to myofibroblasts. CAFs promote cancer cell differentiation and invasion by releasing various factors, such as growth factors, chemokines, and matrix-degrading proteases, into neighboring tumor cells. However, the roles of tumor microenvironment in case of radiation-induced carcinogenesis remain poorly understood. We recently revealed that mitochondrial oxidative stress causes tumor microenvironment formation associated with radiation-induced cancer. Repeated low-dose fractionated radiation progressively damages fibroblast mitochondria and elevates mitochondrial reactive oxygen species (ROS) levels. Excessive mitochondrial ROS activate transforming growth factor-beta (TGF-β) signaling, thereby inducing fibroblasts activation and facilitating tumor microenvironment formation. Consequently, radiation affects malignant cancer cells directly and indirectly via molecular alterations in stromal fibroblasts, such as the activation of TGF-β and angiogenic signaling. This review summarizes for the first time the roles of mitochondrial oxidative stress in microenvironment formation associated with radiation-induced cancer. This review may help us understand the risks of exposure to low-dose radiation. The cross talk between cancer cells and stromal fibroblasts contributes to the development and progression of radiation-induced cancer.

The glutathione (GSH) redox control is critical to maintain redox balance in the body’s internal environment, and its perturbation leads to a dramatic increase in reactive oxygen species (ROS) levels and oxidative stress which have negative impacts on human health. Although ionizing radiation increases mitochondrial ROS generation, the mechanisms underlying radiation-induced late ROS accumulation are not fully understood. Here we investigated the radiation effect on GSH redox reactions in normal human diploid lung fibroblasts TIG-3 and MRC-5. Superoxide anion probe MitoSOX-red staining and measurement of GSH peroxidase (GPx) activity revealed that high dose single-radiation (SR) exposure (10 Gy) increased mitochondrial ROS generation and overall oxidative stress in parallel with decrease in GSH peroxidase (GPx) activity, while GSH redox control was effective after exposure to moderate doses under standard serum conditions. We used different serum conditions to elucidate the role of serum on GSH redox reaction. Serum starvation, serum deprivation and DNA damage response (DDR) inhibitors-treatment reduced the GPx activity and increased mitochondrial ROS generation regardless of radiation exposure. Fractionated-radiation was used to evaluate the radiation effect on GSH reactions. Repeated fractionated-radiation induced prolonged oxidative stress by down-regulation of GPx activity. In conclusion, radiation affects GSH usage according to radiation dose, irradiation methods and serum concentration. Radiation affected the GPx activity to disrupt fibroblast redox homeostasis.

Accidental radiation exposure that is due to a nuclear accident or terrorism using radioactive materials has severe detrimental effects on human health, and it can manifest as acute radiation syndrome depending on the dose and distribution of the radiation. Therefore, the development of radiation countermeasure agents is urgently needed to protect humans against radiation injury. Besides nuclear DNA, the mitochondria are important targets of ionizing radiation (IR) because these organelles generate reactive oxygen species (ROS). Recently, we revealed that mitochondrial ROS-activated cell signaling is associated with IR-induced tumor formation. Here, we investigated the effectiveness of ascorbic acid and epicatechin (EC) in scavenging ROS as radiation countermeasure agents by using human cells and mouse. Preradiation and postradiation treatments with EC mitigate ROS-mediated mitochondrial damage, IR-induced oxidative stress responses including reduction of superoxide dismutase activity, and elevated nuclear factor erythroid 2-related factor 2 expression, and they improve human fibroblast survival. As well as in vitro, EC mitigated ROS-mediated mitochondrial damage after exposure to IR in vivo in mouse platelets. Furthermore, oral administration of EC significantly enhanced the recovery of mouse hematopoietic cells from radiation injury in vivo. In summary, EC is a potentially viable countermeasure agent that is immediately effective against accidental IR exposure by targeting mitochondria-mediated oxidative stress.-Shimura, T., Koyama, M., Aono, D., Kunugita, N. Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells.

A compact near-eye display with a 60° horizontal field of view, wide eye box of 5 mm, and high resolution of 720 p is proposed and developed by combining a transmission hologram that duplicates the beam of a scanning display and a reflection hologram that reflects duplicated beams toward the user’s eye. The feasibility of the proposed near-eye display is demonstrated by examining the specifications and exposure of 24 multiple holograms. A compact NED that can display images with a horizontal FOV of 60° and that has a 6.2 mm × 4.8 mm eye box and 720 pixels vertical resolution is achieved.

Wavelength conversion using plasmonic nanostructures has been attracting attention as a novel nonlinear optical effect occurred in nano-sized regions. In general, the second order nonlinear polarization does not occur in the isotropic metal, while the breaking symmetry on the metal surface is considered to permit the SHG (second harmonic generation). The radiation control of the SHG signal is essential in order to apply plasmonic nanostructures as wave conversion devices. However, its radiation control has been difficult because the second order nonlinear polarization on the metal surface is sensitive to the surface roughness. In this study, we demonstrated the control of the SHG radiation pattern and phase by the unique idea that the second order nonlinear polarization couples to the dipole plasmon mode.

In tumor tissues, activated stromal fibroblasts, termed cancer-associated fibroblasts (CAFs), exhibit similar characteristics to myofibroblasts. CAFs promote cancer cell differentiation and invasion by releasing various factors, such as growth factors, chemokines, and matrix-degrading proteases, into neighboring tumor cells. However, the roles of tumor microenvironment in case of radiation-induced carcinogenesis remain poorly understood. We recently revealed that mitochondrial oxidative stress causes tumor microenvironment formation associated with radiation-induced cancer. Repeated low-dose fractionated radiation progressively damages fibroblast mitochondria and elevates mitochondrial reactive oxygen species (ROS) levels. Excessive mitochondrial ROS activate transforming growth factor-beta (TGF-β) signaling, thereby inducing fibroblasts activation and facilitating tumor microenvironment formation. Consequently, radiation affects malignant cancer cells directly and indirectly via molecular alterations in stromal fibroblasts, such as the activation of TGF-β and angiogenic signaling. This review summarizes for the first time the roles of mitochondrial oxidative stress in microenvironment formation associated with radiation-induced cancer. This review may help us understand the risks of exposure to low-dose radiation. The cross talk between cancer cells and stromal fibroblasts contributes to the development and progression of radiation-induced cancer.

6 pags., 4 figs., Optical force is a powerful tool to actuate micromachines. Conventional approaches often require focusing and steering an incident laser beam, resulting in a bottleneck for the integration of the optically actuated machines. Here, we propose a linear nanomotor based on a plasmonic particle that generates, even when illuminated with a plane wave, a lateral optical force due to its directional side scattering. This force direction is determined by the orientation of the nanoparticle rather than a field gradient or propagation direction of the incident light. We demonstrate the arrangements of the particles allow controlling the lateral force distributions with the resolution beyond the diffraction limit, which can produce movements, as designed, of microobjects in which they are embedded without shaping and steering the laser beam. Our nanomotor to engineer the experienced force can open the door to a new class of micro/nanomechanical devices that can be entirely operated by light., This work was supported by JST PRESTO grant JPMJPR15PA, Japan, and JSPS KAKENHI grant nos. JP19H02533 and JP19H04670 in Scientific Research on Innovative Areas “nanomaterial optical manipulation.” Preliminary studies were performed at Imperial College London, under support of the EPSRC Active Plasmonics Programme (EP/H00917/2). P.A acknowledges Ramon y Cajal Fellowship RYC-2016-20831 and MICINN project PGC2018- 096649-B100. M.R. acknowledges support from the Royal Society and the Wolfson Foundation.

Spin and orbital angular momenta are separately observable properties of light. Both of them can interact with matter, causing an exchange between each other and generating an optical torque on the matter. However, thus far, we have been unable to separately discuss the transfer of the spin and orbital angular momenta or the origin of the optical torques with regard to them. Here, we consider the optical chirality density and propose an approach to analyzing the transfer of spin and orbital angular momenta separately by considering this property. Our approach is based on a continuity equation for spin angular momentum density. This equation is derived from an extended proportional relation between the chirality flux density and spin angular momentum density in sources-added space. Our findings will greatly facilitate the study of angular momentum interaction between light and matter.

32nd Annual Conference of the International Society for Environmental Epidemiology(ISEE2020)；2020.8.24-27；Web（Washinton，DC）

32nd Annual Conference of the International Society for Environmental Epidemiology(ISEE2020)；2020.8.24-27；Web（Washinton，DC）

We report that localized surface plasmon resonance allows a single-element nanostructure to induce an extrinsic angular momentum of light in its interaction with a propagating plane wave. The recoil of the angular momentum results in an optical torque on the structure along an axis perpendicular to the optical axis, and the characteristics of this transverse torque depend on the incident polarization state, including the spin direction. Our results suggest that the designed dark plasmon mode can provide a new degree of freedom for optical manipulation of nanoparticles smaller than the diffraction limit.

We observed spin-wave transmission through an air gap that works as a prohibited region. The spin waves were excited by circularly polarized pump pulses via the inverse Faraday effect, and their spatial propagation was detected through the Faraday effect of probe pulses using a pump-probe imaging technique. The experimentally observed spin-wave transmission was reproduced using numerical calculations with a Green's function method and micromagnetic simulation. We found that the amplitude of the spin waves decays exponentially in the air gap, which indicates the existence of evanescent spin waves in the magnetic dipole regime. This finding will pave the way for controllable amplitudes and phases of spin waves propagating through an artificial magnonic crystal., 13 pages, 4 figures

We present a numerical study of optical torque between two twisted metal nanorods due to the angular momentum of the electromagnetic field emerging from their plasmonic coupling. Our results indicate that the interaction optical torque on the nanorods can be strongly enhanced by their plasmon coupling, which highly depends on not only the gap size but also the twisted angle between the nanorods. The behaviors of the optical torque are different between two plasmon coupling modes: hybridized bonding and anti-bonding modes with different resonances. The rotations of the twisted nanorods with the bonding and anti-bonding mode excitations lead to mutually parallel and perpendicular alignments, respectively. At an incident intensity of 10 mW/μm2, the rotational potential depths are more than 30 times as large as the Brownian motion energy, enabling the optical alignments with angle fluctuations less than ∼±10°. Thus, this optical alignment of the nanoparticles with the plasmon coupling allows dynamic control of the plasmonic characteristics and functions.

Dose assessment is an important issue for radiation emergency medicine to determine appropriate clinical treatment. Hematopoietic tissues are extremely vulnerable to radiation exposure. A decrease in blood cell count following radiation exposure is the first quantitative bio-indicator using hematological techniques. We further examined induction of oxidative stress biomarkers in residual lymphocytes to identify new biomarkers for dosimetry. In vivo whole-body radiation to mice exposed to 5 Gy significantly induces DNA double-strand breaks, which were visualized by γ-H2AX in mouse blood cells. Mouse blood smears and peripheral blood mononuclear cells (PBMC) isolated from irradiated mice were used for immunostaining for oxidative biomarkers, parkin or Nrf2. Parkin is the E3 ubiquitin ligase, which is normally localized in the cytoplasm, is relocated to abnormal mitochondria with low membrane potential (ΔΨm), where it promotes clearance via mitophagy. Nrf2 transcription factor controls the major cellular antioxidant responses. Both markers of oxidative stress were more sensitive and persistent over time than nuclear DNA damage. In conclusion, parkin and Nrf2 are potential biomarkers for use in radiation dosimetry. Identification of several biological markers which show different kinetics for radiation response is essential for radiation dosimetry that allows the assessment of radiation injury and efficacy of clinical treatment in emergency radiation incidents. Radiation-induced oxidative damage is useful not only for radiation dose assessment but also for evaluation of radiation risks on humans.

Dose assessment is an important issue for radiation emergency medicine to determine appropriate clinical treatment. Hematopoietic tissues are extremely vulnerable to radiation exposure. A decrease in blood cell count following radiation exposure is the first quantitative bio-indicator using hematological techniques. We further examined induction of oxidative stress biomarkers in residual lymphocytes to identify new biomarkers for dosimetry. In vivo whole-body radiation to mice exposed to 5 Gy significantly induces DNA double-strand breaks, which were visualized by γ-H2AX in mouse blood cells. Mouse blood smears and peripheral blood mononuclear cells (PBMC) isolated from irradiated mice were used for immunostaining for oxidative biomarkers, parkin or Nrf2. Parkin is the E3 ubiquitin ligase, which is normally localized in the cytoplasm, is relocated to abnormal mitochondria with low membrane potential (ΔΨm), where it promotes clearance via mitophagy. Nrf2 transcription factor controls the major cellular antioxidant responses. Both markers of oxidative stress were more sensitive and persistent over time than nuclear DNA damage. In conclusion, parkin and Nrf2 are potential biomarkers for use in radiation dosimetry. Identification of several biological markers which show different kinetics for radiation response is essential for radiation dosimetry that allows the assessment of radiation injury and efficacy of clinical treatment in emergency radiation incidents. Radiation-induced oxidative damage is useful not only for radiation dose assessment but also for evaluation of radiation risks on humans.

Fibroblasts are a key stromal cell in the tumor microenvironment (TME) and promote tumor growth via release of various growth factors. Stromal fibroblasts in cancer, called cancer-associated fibroblasts (CAF), are related to myofibroblasts, an activated form of fibroblast. While investigating the role of stroma fibroblasts on radiation-related carcinogenesis, it was observed following long-term fractionated radiation (FR) that the morphology of human diploid fibroblasts changed from smaller spindle shapes to larger flat shapes. These cells expressed smooth muscle actin (α-SMA) and platelet-derived growth factor receptors, markers of myofibroblasts and CAFs, respectively. Long-term FR induces progressive damage to the fibroblast nucleus and mitochondria via increases in mitochondrial reactive oxygen species (ROS) levels. Here, it is demonstrated that long-term FR-induced α-SMA–positive cells have decreased mitochondrial membrane potential and activated oxidative stress responses. Antioxidant N-acetyl cysteine suppressed radiation-induced mitochondrial damage and generation of myofibroblasts. These results indicate that mitochondrial ROS are associated with the acquisition of myofibroblasts after long-term FR. Mechanistically, mitochondrial ROS activated TGFβ signaling which in turn mediated the expression of α-SMA in radiation-induced myofibroblasts. Finally, in vivo tumor growth analysis in a human tumor xenograft model system revealed that long-term FR-induced myofibroblasts promote tumor growth by enhancing angiogenesis. Implications: Radiation affects malignant cancer cells directly and indirectly via molecular alterations in stromal fibroblasts such as activation of TGFβ and angiogenic signaling pathways. Mol Cancer Res; 16(11); 1676–86. ©2018 AACR.

In order to improve the performance of localized surface plasmon resonance (LSPR) sensors, lattice plasmons of plasmonic nanoparticle (NP) arrays are often used. The lattice plasmon sensors based on coupling between LSPR of each NP and diffraction of the NP array generally have a higher ability to detect local refractive index changes than conventional LSPR sensors based on random NP ensembles. However, the surface selectivity of the lattice plasmon sensors is lower than that of the LSPR sensors because the local electric field of the former extends far from the particle array surface. In this work, we develop a novel plasmonic–diffractive hybrid sensor that can simultaneously determine both local and bulk refractive indices from two output signals, namely, extinction dip and peak, the wavelengths of which are differently dependent on those indices. The hybrid sensor can evaluate the refractive index changes in the immediate vicinity of the sensor surface by canceling the difference in the bulk refractive...

Phenanthrenequinone (PQ) doped poly-(methyl methacrylate) (PMMA) have been proven to be available material for volume polarization holographic recording. In our work, we introduced benzyl methacrylate (BzMA) into the PQ/PMMA to increase the concentration of PQ (up to 1.15wt%) within the polymeric media. The enhancement of concentration of PQ brings a mean for improving performance of material. Compared with the pure PQ/PMMA, photoinduced birefringence and diffraction intensity were multiplied by introducing BzMA. This investigation can provide a significant foundation for improving polarization holographic characteristics of PQ/PMMA by modifying the chemical composition of the material.

The health effects of tritium are a major public concern in Japan due to the presence of tritium (HTO) contaminated water at the Fukushima Dai-ichi Nuclear Power Plant (Fukushima NPP). From a scientific view, the biological effects of the contaminant HTO at the Fukushima NPP could conceivably be quite small, but the possibility of stochastic effects from tritium radiation cannot be neglected. This reasoning is based on the linear no-threshold (LNT) model, which is cited in ICRP recommendations and suggests an elevation in the frequency of the stochastic effects of radiation, even when the doses are less than 100 mGy. However, at the present, only a small amount of experimental data is available describing the biological effects of low doses radiation, and there are no established experimental systems that can clearly show whether or not the LNT model is appropriate. This is due to a wide scatter in data for the incidence of stochastic effects, which makes it difficult to distinguish radiation-induced events from spontaneous events. We propose overcoming this difficulty for radiobiology experiments using low doses or low dose rate radiation by establishing hypersensitive assay systems, and report on the current status of work investigating tritium radiobiology in Japan.

The chiroptical response of most naturally occurring chiral materials is generally very weak, which discourages further studies and limits applications. Recently, chiral plasmonic structures have received significant attention because of their large chiroptical response. Note that the interaction between the constituents is extremely important and indispensable to the chiroptical response in a chiral plasmonic system. Here, we extend the study of chiroptical response concerning the interaction between the constituents to a strong plasmon coupling regime based on the dimer of twisted metal nanorods. To this end, we realize the fabrication of twisted nanorods with a small gap size of ~15 nm to ensure that we can observe the separated hybridized modes generated by the plasmon coupling between the twisted nanorods. The dependence of the plasmon coupling and dissymmetry factor on the gap size and twisted angle clearly demonstrates that the plasmon coupling followed by the hybridization strongly enhances the chiroptical response. The dissymmetry factor of the experimentally optimized structures reached values of up to ~1.03, which is much larger than other nano-plasmonic systems of the same order of dimension. Furthermore, the chiroptical response, as well as the plasmon coupling, is very sensitive to the configuration of the structure, which means that they are precisely controlled by tuning the gap size and twisted angle. Our study that is based on the plasmon coupling provides a further understanding of the study of chiroptical response and will assist in the future design and improvement of chiral plasmonic structures for metamaterial applications.

The unique properties of graphene plasmons show great potential for plasmonic nanodevice applications such as sensors and modulators. Graphene plasmon launching, propagation control, and ultimately launching with directional control are therefore crucial for the development of such devices. However, previous studies have used foreign objects or external influencing factors to attain directional plasmon launching on graphene, which introduce defects and add complexity to the system. This study introduces a theoretical framework for a graphene-only approach to direction-controlled plasmon launching. We use graphene nanoridges, a defect-free natural structure of graphene, as a plasmon launcher. Through proper arrangement of the nanoridges, unidirectional, bidirectional, and wavelength-sorted plasmon launching with normal illumination can be achieved.

Ultrafast control of magnets using femtosecond light pulses attracts interest regarding applications and fundamental physics of magnetism. Antiferromagnets are promising materials with magnon frequencies extending into the terahertz range. Visible or near-infrared light interacts mainly with the electronic orbital angular momentum. In many magnets, however, in particular with iron-group ions, the orbital momentum is almost quenched by the crystal field. Thus, the interaction of magnons with light is hampered, because it is only mediated by weak unquenching of the orbital momentum by spin–orbit interactions. Here we report all-optical excitation of magnons with frequencies up to 9 THz in antiferromagnetic CoO with an unquenched orbital momentum. In CoO, magnon modes are coupled oscillations of spin and orbital momenta with comparable amplitudes. We demonstrate excitations of magnon modes by directly coupling light with electronic orbital angular momentum, providing possibilities to develop magneto-optical devices operating at several terahertz with high output-to-input ratio., 超短光パルスで磁性体中に大振幅テラヘルツ・スピン波を励起 --超高速・高効率磁気光学デバイスへ期待--. 京都大学プレスリリース. 2017-09-29.

I will introduce test items and measuring methods for camera lenses in the “New Face Clinic” of the “Photography Journal, Asahi Camera” that is a monthly magazine for camera and photo enthusiasts. In that article, we introduce the lens configuration, special glass material, aspheric surfaces, coating type first. The main test items are focal length, open aperture value, spherical aberration, curvature of field, astigmatism, distortion, and modulation transfer function (MTF). Also, we actually shoot distant views, point light sources, close-up shots and evaluate images through the eyes. Although the test results are mixture of the effect of the image processing and physical lens performance, we measure Spatial Frequency Response (SFR). Finally, we evaluate the lenses comprehensively from these test results.

We report that localized surface plasmon resonance allows a single-element nanostructure to induce an extrinsic angular momentum of light in its interaction with a propagating plane wave. The recoil of the angular momentum results in an optical torque on the structure along an axis perpendicular to the optical axis, and the characteristics of this transverse torque depend on the incident polarization state, including the spin direction. Our results suggest that the designed dark plasmon mode can provide a new degree of freedom for optical manipulation of nanoparticles smaller than the diffraction limit.

Ataxia telangiectasia (AT) is characterized by extreme sensitivity to ionizing radiation. The gene mutated in AT, Ataxia Telangiectasia Mutated (ATM), has serine/threonine protein kinase activity and mediates the activation of multiple signal transduction pathways involved in the processing of DNA double-strand breaks. Reactive oxygen species (ROS) created as a byproduct of the mitochondria’s oxidative phosphorylation (OXPHOS) has been proposed to be the source of intracellular ROS. Mitochondria are uniquely vulnerable to ROS because they are the sites of ROS generation. ROS-induced mitochondrial mutations lead to impaired mitochondrial respiration and further increase the likelihood of ROS generation, establishing a vicious cycle of further ROS production and mitochondrial damage. AT patients and ATM-deficient mice display intrinsic mitochondrial dysfunction and exhibit constitutive elevations in ROS levels. ATM plays a critical role in maintaining cellular redox homeostasis. However, the precise mechanism of ATM-mediated mitochondrial antioxidants remains unclear. The aim of this review paper is to introduce our current research surrounding the role of ATM on maintaining cellular redox control in human fibroblasts. ATM-mediated signal transduction is important in the mitochondrial radiation response. Perturbation of mitochondrial redox control elevates ROS which are key mediators in the development of cancer by many mechanisms, including ROS-mediated genomic instability, tumor microenvironment formation, and chronic inflammation.

Radiotherapy (RT) is a powerful tool in the treatment of cancer, having the advantage of preserving normal tissues. Clinical outcomes of RT are significantly improved by technological advances, enabling increased radiation doses directed very specifically to a tumor. However, tumor radioresistance remains a major impediment to effective RT. We have shown that human tumor cells surviving after repeated exposure to fractionated radiation (FR) of X-rays for 1 month have acquired radioresistance through constitutive activation of AKT and downstream cyclin D1 nuclear retention. Tumor radioresistance is also proposed to be an intrinsic characteristic of cancer stem cells (CSC), whose efficient DNA repair is thought to confer this phenotype. We have isolated radioresistant CD133-positive cells following exposure to long-term FR. These cells exhibited the CSC phenotype with activation of the AKT/cyclin D1 pathway. In this review, I summarize our current understanding of the molecular mechanisms underlying tumor radioresistance and propose a strategy for overcoming radioresistance by targeting the AKT/cyclin D1 pathway.Two different mechanisms: acquired radioresistance of surviving tumor cells after RT and intrinsic radioresistance of CSC are associated with tumor radioresistance. Inhibition of the AKT pathway results in radiosensitization of both types of tumor radioresistance.

A new photovoltaic generation unit based on the application of holographic technologies called a Holo-Window is proposed in this work. The basic principle and the optical configuration used for the basic experimental unit are described. Suitable fabrication technology for a hologram with the broadband spectrum required to provide the appropriate sunlight capture capability is then discussed. Finally, a laboratory-prototype Holo-Window unit was developed and its performance was evaluated.

Mitochondria are associated with various radiation responses, including adaptive responses, mitophagy, the bystander effect, genomic instability, and apoptosis. We recently identified a unique radiation response in the mitochondria of human cells exposed to low-dose long-term fractionated radiation (FR). Such repeated radiation exposure inflicts chronic oxidative stresses on irradiated cells via the continuous release of mitochondrial reactive oxygen species (ROS) and decrease in cellular levels of the antioxidant glutathione. ROS-induced oxidative mitochondrial DNA (mtDNA) damage generates mutations upon DNA replication. Therefore, mtDNA mutation and dysfunction can be used as markers to assess the effects of low-dose radiation. In this study, we present an overview of the link between mitochondrial ROS and cell cycle perturbation associated with the genomic instability of low-dose irradiated cells. Excess mitochondrial ROS perturb AKT/cyclin D1 cell cycle signaling via oxidative inactivation of protein phosphatase 2A after low-dose long-term FR. The resulting abnormal nuclear accumulation of cyclin D1 induces genomic instability in low-dose irradiated cells.