Latent ion tracks were finally observed in diamond.

Injecting high-energy heavy ions in the electronic stopping regime into solids can create cylindrical damage zones called latent ion tracks. Although these tracks form in many materials, none have ever been observed in diamond, even when irradiated with high-energy GeV uranium ions. Here we report the first observation of ion track formation in diamond irradiated with 2-9 MeV C60 fullerene ions. Depending on the ion energy, the mean track length (diameter) changed from 17 (3.2) nm to 52 (7.1) nm. High resolution scanning transmission electron microscopy (HR-STEM) indicated the amorphization in the tracks, in which π-bonding signal from graphite was detected by the electron energy loss spectroscopy (EELS). Since the melting transition is not induced in diamond at atmospheric pressure, conventional inelastic thermal spike calculations cannot be applied. Two-temperature molecular dynamics simulations succeeded in the reproduction of both the track formation under MeV C60 irradiations and the no-track formation under GeV monoatomic ion irradiations.

Historical record of polychlorinated biphenyls in a sediment core from Lake Biwa, Japan: Significance of unintentional emission and weathering signals revealed by full congener-specific analysis.

The occurrence of 209 PCB congeners was determined in a sediment core dated between 1930 and 2019 from Lake Biwa, a typical temperate monomictic lake in Japan. Concentrations of total PCBs ranged from 5.3 to 48 ng/g dry weight (dw), showing a highest peak at the 1960s to 1970s. The temporal trend of total PCBs in this sediment core generally matched with Japanese PCB production and emission pattern (i.e., increasing from the 1950s, peaking at 1970, and gradually decreasing since 1972). The vertical PCB profiles in our core were affected by physical mixing and bioturbation. By using a detailed and comprehensive analytical method, we have found elevated concentrations and special historical profiles of several congeners such as CB-7, -11, -47/48/75, -51, -68, and -209, which are still rarely included in routine PCB analysis. Some tetra-CB congeners like CB-47/48/75, -51, and -68 showed their concentration peaks at the early 2010s, which may be unintentionally produced during polymer manufacturing processes. PCB homolog- and congener-specific profiles in our sediment core samples have experienced weathering with higher proportions of penta- and hexa-CBs as compared to the Kanechlor usage pattern (i.e., dominated by tri- and tetra-CBs). Both intentional (i.e., technical mixtures) and unintentional (e.g., PCB-containing polymers and pigments) sources of PCBs were suggested from congener-specific analysis.

Determination of brominated flame retardants including polybrominated diphenyl ethers, pentabromoethylbenzene, hexabromobiphenyl, and decabromodiphenyl ethane in sediment samples: Validation of a rapid and efficient clean-up method and application to a sediment core from Lake Biwa, Japan.

The development of rapid and efficient analytical method for the determination of legacy and current-use brominated flame retardants (BFRs) has been performed due to environmental concern related to these pollutants. In the present study, we used an automated clean-up device equipped with pre-packed micro-column sets (containing sulfuric acid impregnated silica gel and silver-modified alumina) to develop an effective purification method for polybrominated diphenyl ethers (PBDEs), pentabromoethylbenzene, hexabromobiphenyl, and decabromodiphenyl ethane (DBDPE) in sediment extracts. Matrix-spiked sediments (n = 6) and the Standard Reference Material® 1944 samples (n = 6) were tested. Our method showed acceptable accuracy, repeatability, and sensitivity for almost all the target compounds with reduced processing time, labor requirement, and solvent amounts as compared to conventional clean-up method (e.g., sulfuric acid treatment and self-packed chromatographic columns). The validated method was applied to sediment core samples (n = 16) collected in 2019 from Lake Biwa, the largest lake in Japan. PBDEs were detected in sediment samples of 0-13 cm depth (dated between 1990 and 2019) at relatively low concentrations (median 5.7; range 2.6-9.4 ng/g dry weight). PBDE profiles were dominated by BDE-209, which accounted for 91 ± 10% of total PBDEs. Among other BFRs, only DBDPE was found in sediment layers of 0-9 cm depth (deposited between 2005 and 2019). DBDPE concentrations ranged from 0.43 to 1.6 (median 0.71) ng/g and showed increasing trend toward shallower depths.

Ion tracks in silicon formed by much lower energy deposition than the track formation threshold.

Damaged regions of cylindrical shapes called ion tracks, typically in nano-meters wide and tens micro-meters long, are formed along the ion trajectories in many insulators, when high energy ions in the electronic stopping regime are injected. In most cases, the ion tracks were assumed as consequences of dense electronic energy deposition from the high energy ions, except some cases where the synergy effect with the nuclear energy deposition plays an important role. In crystalline Si (c-Si), no tracks have been observed with any monomer ions up to GeV. Tracks are formed in c-Si under 40 MeV fullerene (C60) cluster ion irradiation, which provides much higher energy deposition than monomer ions. The track diameter decreases with decreasing the ion energy until they disappear at an extrapolated value of ~ 17 MeV. However, here we report the track formation of 10 nm in diameter under C60 ion irradiation of 6 MeV, i.e., much lower than the extrapolated threshold. The diameters of 10 nm were comparable to those under 40 MeV C60 irradiation. Furthermore, the tracks formed by 6 MeV C60 irradiation consisted of damaged crystalline, while those formed by 40 MeV C60 irradiation were amorphous. The track formation was observed down to 1 MeV and probably lower with decreasing the track diameters. The track lengths were much shorter than those expected from the drop of Se below the threshold. These track formations at such low energies cannot be explained by the conventional purely electronic energy deposition mechanism, indicating another origin, e.g., the synergy effect between the electronic and nuclear energy depositions, or dual transitions of transient melting and boiling.

Matrix-material dependence on the elongation of embedded gold nanoparticles induced by 4 MeV C60 and 200 MeV Xe ion irradiation.

We report the elongation of embedded Au nanoparticles (NPs) in three different matrices, i.e. amorphous carbon (a-C), crystalline indium tin oxide (InxSn1-xOz; ITO) and crystalline calcium fluoride (CaF2), under irradiations of 4 MeV C60 + cluster ions and 200 MeV Xe14+ ions. Under 4 MeV C60 cluster irradiation, strong sputtering is induced in CaF2 layer so that the whole the layer was completely lost at a fluence of 5 × 1013 ions cm-2. Au NPs were partly observed in the SiO2, probably due to the recoil implantation. Amorphous carbon (a-C) layer exhibits low sputtering loss even under 4 MeV C60 irradiation. However, the elongation in a-C layer was low. While the ITO layer showed a certain decrease in thickness under 4 MeV C60 irradiation, large elongation of Au NPs was observed under both 4 MeV C60 and 200 MeV Xe irradiation. The ITO layer preserved the crystallinity even after large elongation was induced. This is the first report of the elongation of metal NPs in a crystalline matrix.

Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

C60 ions of 1 MeV are slow but elongate nanoparticles like swift heavy ions of hundreds MeV.

This study reports that high fluence fullerene ion (C60+) irradiation of 1-6 MeV, which was made possible by a new-type of high-flux ion source, elongates metal nanoparticles (NPs) in amorphous SiO2 as efficiently as swift heavy ions (SHIs) of 200 MeV Xe14+, i.e., two orders of the magnitude higher energy ions. Comparing the irradiation effects induced by both the beams, the stopping processes of C60 ions in SiO2 are discussed in this paper. Despite of having almost the same elongation efficiency, the C60+ irradiation induced ~10 times more efficient sputtering due to the clustering enhancement and/or the synergy effect. Ion tracks of ~10.4 nm in diameter and 60-80 nm in length were observed in crystalline SiO2 under 4 MeV C60 irradiation. While the track diameter was comparable to those by SHIs of the same electronic stopping, much shorter track lengths than those predicted by a rigid C60 molecule model indicates that the fragmentation occurred due to nuclear collisions. The elongation of the metal NPs was induced only down to the depth where the tracks were observed but not beyond.

Characterization of secondary ion emission processes of sub-MeV C60 ion impacts via analysis of statistical distributions of the emitted ion number.

We report probability distributions of the number of secondary ions (SIs) emitted by sub-MeV C60 ion impacts on an organic polymer target and the characterization of their emission processes through the analysis of the distributions. The probability distributions were obtained by analyzing experimental SI counting data obtained by a time-of-flight SI mass spectrometer combined with pulsed primary ion beams, using an analytical model developed to derive the distributions from the experimental data. A series of probability distribution functions was investigated for ion impacts of C60 with sub-MeV energies (0.12-0.54 MeV), which can provide sufficient SIs per impact to determine the functions. Their complicated and undefined SI emission processes were characterized based on the determined functions.

Historical changes in the ecosystem condition of a small mountain lake over the past 60 years as revealed by plankton remains and Daphnia ephippial carapaces stored in lake sediments.

To examine if changes in species composition of a plankton community in the past due to anthropogenic activities can be clarified in lakes without any monitoring data, we analyzed genetically ephippial carapaces of Daphnia with plankton remains stored in the bottom sediments of Lake Hataya Ohunma in Japan. In the lake, abundance of most plankton remains in the sediments was limited and TP flux was at low levels (2-4 mg/m2/y) before 1970. However TP flux increased two-fold during the period from 1980s to 1990 s. In parallel with this increase, abundance of most plankton remains increased although abundance of benthic testate amoebae's remains decreased, indicating that the lake trophic condition had changed from oligo- to mesotrophic for the past 60 years. According to cluster analysis, the stratigraphic sediments were divided into two periods with different features of the phytoplankton composition. Chronological comparison with events in the watershed suggested that eutrophication occurred because of an increase in visitors to the watershed and deposition of atmospheric dust. In this lake more than 50% of resting eggs produced by Daphnia over the past 60 years hatched. However, genetic analysis of the ephippial carapaces (remains) showed that the Daphnia population was originally composed of D. dentifera but that D. galeata, or its hybrid with D. dentifera, invaded and increased the population density when the lake was eutrophied. Subsequently, large D. pulex established populations in the 1980s when largemouth bass were anonymously introduced. These results indicated that the Lake Hataya Ohunma plankton community underwent significant changes despite the fact that there were no notable changes in land cover or land use in the watershed. Since increases in atmospheric deposition and release of fish have occurred in many Japanese lakes, the changes in the plankton community described here may be widespread in these lakes.

Type I IFN gene delivery suppresses regulatory T cells within tumors.

Type I interferon (IFN) is a pleiotropic cytokine regulating the cancer cell death and immune response. IFN-α can, as we have also reported, effectively induce an antitumor immunity by the activation of tumor-specific T cells and maturation of dendritic cells in various animal models. Unknown, however, is how the type I IFN alters the immunotolerant microenvironment in the tumors. Here, we found that intratumoral IFN-α gene transfer significantly decreased the frequency of regulatory T cells (Tregs) per CD4(+) T cells in tumors. The concentration of a Treg-inhibitory cytokine, interleukin (IL)-6, was correlated with the IFN-α expression level in tumors, and intratumoral CD11c(+) cells produced IL-6 in response to IFN-α stimulation. To confirm the role of IL-6 in the suppression of Tregs in tumors, an anti-IL-6 receptor antibody was administered in IFN-α-treated mice. The antibody increased the frequency of Tregs in the tumors, and attenuated systemic tumor-specific immunity induced by IFN-α. Furthermore, the IFN-α-mediated IL-6 production increased the frequency of Th17 cells in the tumors, which may be one of the mechanisms for the reduction of Tregs. The study demonstrated that IFN-α gene delivery creates an environment strongly supporting the enhancement of antitumor immunity through the suppression of Tregs.

Time-of-flight secondary ion mass spectrometry with transmission of energetic primary cluster ions through foil targets.

We developed time-of-flight (TOF) secondary ion (SI) mass spectrometry that provides informative SI ion mass spectra without needing a sophisticated ion beam pulsing system. In the newly developed spectrometry, energetic large cluster ions with energies of the order of sub MeV or greater are used as primary ions. Because their impacts on the target surface produce high yields of SIs, the resulting SI mass spectra are informative. In addition, the start signals necessary for timing information on primary ion incidence are provided by the detection signals of particles emitted from the rear surface of foil targets upon transmission of the primary ions. This configuration allows us to obtain positive and negative TOF SI mass spectra without pulsing system, which requires precise control of the primary ions to give the spectra with good mass resolution. We also successfully applied the TOF SI mass spectrometry with energetic cluster ion impacts to the chemical structure characterization of organic thin film targets.

In vivo comet assay of a novel galacto-oligosaccharide in rats.

A novel galacto-oligosaccharide (GOS) manufactured by a two-step enzyme reaction of lactose was examined in a comet assay for its potential to induce DNA damage in vivo by estimating the DNA fragmentation level in the cellular nuclei of the glandular stomach, colon, and peripheral blood. GOS was orally administered at doses of 0 (vehicle alone), 500, 1000, and 2000 mg/kg/day to five male Crl: CD(Sprague Dawley) rats per group three times (48, 24, and 3 h before the animals were terminated). The specimens were prepared in accordance with the standard protocol (version 14.2) of the "International Validation of the In Vivo Rodent Alkaline Comet Assay for the Detection of Genotoxic Carcinogens" organized by the Japanese Center for the Validation of Alternative Methods. No significant differences in the percentage of DNA in the tail were observed between the GOS-treated groups and vehicle controls in any of the organs evaluated. Additionally, no GOS-related clinical signs or effects on body weight were seen. Based on these results, the comet assay of GOS in the glandular stomach, colon, and peripheral blood using rats was judged negative. Therefore, it is concluded that GOS did not induce DNA damage in vivo under the conditions employed in this study.

Sedimentary records of metal deposition in Japanese alpine lakes for the last 250 years: recent enrichment of airborne Sb and In in East Asia.

Concentrations of 18 elements, including Sb, In, Sn, and Bi, were measured in sediment cores from two pristine alpine lakes on Mount Hachimantai, northern Japan, representing the past 250 years. Vertical variations in concentrations are better explained by atmospheric metal deposition than by diagenetic redistribution of Fe and Mn hydroxide and organic matter. Anthropogenic metal fluxes were estimated from (210)Pb-derived accumulation rates and metal concentrations in excess of the Al-normalized mean background concentration before 1850. Anthropogenic fluxes of Sb and In showed gradual increases starting around 1900 in both lakes, and marked increases after 1980. Comparison of Sb/Pb and Pb stable isotope ratios in sediments with those in aerosols of China or northern Japan and Japanese source materials (recent traffic- and incinerator-derived dust) suggest that the markedly elevated Sb flux after 1980 resulted primarily from enhanced long-range transport in aerosols containing Sb and Pb from coal combustion on the Asian continent. The fluxes of In, Sn, and Bi which are present in Chinese coal showed increasing trends similar to Sb for both study lakes. This suggests that the same source although incinerators in Japan may not be ruled out as sources of In. The sedimentary records for the last 250 years indicate that atmospheric pollution of Sb and In in East Asia have intensified during recent decades.

Tunable nanometer electrode gaps by MeV ion irradiation.

We report the use of MeV ion-irradiation-induced plastic deformation of amorphous materials to fabricate electrodes with nanometer-sized gaps. Plastic deformation of the amorphous metal Pd(80)Si(20) is induced by 4.64 MeV O(2+) ion irradiation, allowing the complete closing of a sub-micrometer gap. We measure the evolving gap size in situ by monitoring the field emission current-voltage (I-V) characteristics between electrodes. The I-V behavior is consistent with Fowler-Nordheim tunneling. We show that using feedback control on this signal permits gap size fabrication with atomic-scale precision. We expect this approach to nanogap fabrication will enable the practical realization of single molecule controlled devices and sensors.

In vivo delivery of interferon-α gene enhances tumor immunity and suppresses immunotolerance in reconstituted lymphopenic hosts.

T cells recognize tumor-associated antigens under the condition of lymphopenia-induced homeostatic proliferation (HP); however, HP-driven antitumor responses gradually decay in association with tumor growth. Type I interferon (IFN) has important roles in regulating the innate and adaptive immune system. In this study we examined whether a tumor-specific immune response induced by IFN-α could enhance and sustain HP-induced antitumor immunity. An intratumoral IFN-α gene transfer resulted in marked tumor suppression when administered in the early period of syngeneic hematopoietic stem cell transplantation (synHSCT), and was evident even in distant tumors that were not transduced with the IFN-α vector. The intratumoral delivery of the IFN-α gene promoted the maturation of CD11c(+) cells in the tumors and effectively augmented the antigen-presentation capacity of the cells. An analysis of the cytokine profile showed that the CD11c(+) cells in the treated tumors secreted a large amount of immune-stimulatory cytokines including interleukin (IL)-6. The CD11c(+) cells rescued effector T-cell proliferation from regulatory T-cell-mediated suppression, and IL-6 may have a dominant role in this phenomenon. The intratumoral IFN-α gene transfer creates an environment strongly supporting the enhancement of antitumor immunity in reconstituted lymphopenic recipients through the induction of tumor-specific immunity and suppression of immunotolerance.

Secondary ion counting for surface-sensitive chemical analysis of organic compounds using time-of-flight secondary ion mass spectroscopy with cluster ion impact ionization.

We report suitable secondary ion (SI) counting for surface-sensitive chemical analysis of organic compounds using time-of-flight (TOF) SI mass spectroscopy, based on considerably higher emission yields of SIs induced by cluster ion impact ionization. A SI counting system for a TOF SI mass spectrometer was developed using a fast digital storage oscilloscope, which allows us to perform various types of analysis as all the signal pulses constituting TOF SI mass spectra can be recorded digitally in the system. Effects of the SI counting strategy on SI mass spectra were investigated for C(8) and C(60) cluster ion impacts on an organically contaminated silicon wafer and on polytetrafluoroethylene targets by comparing TOF SI mass spectra obtained from the same recorded signals with different SI counting procedures. Our results show that the use of a counting system, which can cope with high SI yields, is necessary for quantitative analysis of SI mass spectra obtained under high SI yield per impact conditions, including the case of cluster ion impacts on organic compounds.

Regulation of acrosome reaction of fowl spermatozoa: evidence for the involvement of protein kinase C and protein phosphatase-type 1 and/or -type 2A.

The signal transduction pathways involved in the regulation of the acrosome reaction and motility of fowl spermatozoa were investigated. The motility and acrosomal integrity of fowl spermatozoa in TES/NaCl buffer, with or without homogenised inner perivitelline layers (IPVL), prepared from laid fowl eggs, was almost negligible at 40 degrees C. In the presence of 2 mmol CaCl(2)/l at 40 degrees C, motility became vigorous and the acrosome reaction was stimulated when IPVL was added. In the absence of Ca(2+), motility was stimulated by the addition of calyculin A and okadaic acid, both specific inhibitors of protein phosphatase-type 1 (PP1) and -type 2A (PP2A), but Okadaic acid, which is a weaker inhibitor of PP1, did not completely restore motility at 40 degrees C. However, the acrosome reaction was significantly and equally stimulated in a dose-dependent manner by both inhibitors in the range of 10-1000 nmol/l, when spermatozoa were incubated with IPVL but without Ca(2+). These inhibitors did not stimulate the acrosome reaction in the absence of IPVL. The vigorous motility of spermatozoa, stimulated by the addition of Ca(2+), was reduced gradually as the concentrations of SC-9, a selective activator of protein kinase C (PKC), were increased and a similar SC-9-induced inhibition was observed in the acrosome reaction in the presence of Ca(2+) and IPVL. These results confirm that IPVL is necessary for the activation of the acrosome reaction in fowl spermatozoa and that Ca(2+) plays an important role in the stimulation of motility and acrosomal exocytosis. Furthermore, it appears that the intracellular molecular mechanisms for the regulation of acrosome reaction of fowl spermatozoa are different from those for the restoration of motility, i.e., protein dephosporylation involving PP1 and/or PP2A in the former, and PP1 alone in the latter case. In addition, the activation of PKC may contribute to a decrease in the flagellar movement and acrosome reaction of fowl spermatozoa.

Successful case of adult ABO-incompatible liver transplantation: beneficial effects of intrahepatic artery infusion therapy: a case report.

BACKGROUND: In Japan ABO-incompatible liver transplantation has been done on >100 occasions up to 2003. However, <30% are cases involving adults. The difficultly of ABO-incompatible liver transplantation is associated with the high frequency of humoral rejection and local disseminated intravascular coagulation (DIC), leading to many postoperative complications. We report a successful case of adult ABO-incompatible liver transplantation with the use of an intrahepatic artery infusion. METHODS: A 36-year-old man with Wilson disease, underwent living donor liver transplantation from an ABO-incompatible donor. The immunosuppressive therapy included multiple perioperative plasmaphereses, splenectomy, and treatment with tacrolimus, methylprednisolone, and cyclophosphamide. The dose and blood level of tacrolimus were the same as in ABO-compatible cases. In addition to these therapies, we administered an intrahepatic arterial infusion with prostaglandin (PG) E1 alone. RESULTS: After perioperative plasmapheresis and cyclophosphamide, antidonor blood group antibody titers remained undiluted and without vascular complications throughout the postoperative course, but there was a tendency for bleeding that continued for 10 days after transplantation. On postoperative day 10, a reexploration was performed for intraabdominal bleeding. During another operation on postoperative day 59 a biloma was found and drained. The patient has now survived for 120 days after transplantation with normal liver function. CONCLUSIONS: Beneficial effect of intrahepatic artery infusion with PGE1 seems to be useful in adult ABO-incompatible liver transplantation.