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How Epstein–Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (DLBCL) occasionally occurs following chronic inflammation remains to be elucidated. The case of a 57‐year‐old man who developed pulmonary EBV‐positive DLBCL from underlying silicosis lesions is presented. Immunohistochemical examination of the resected silicosis lesions showed predominant helper T cells and M1/M2 macrophages, with a lack of B cells, regulatory T cells, and resident memory T cells. Two years later, EBV‐positive DLBCL emerged unexpectedly from the silicosis. The imbalance of the immune cells in the microenvironment, at least in part, may help explain how chronic inflammation contributes to EBV‐positive DLBCL., The underlying silicosis lesions showed predominant Th cells and M1/M2 macrophages, with a lack of B cells, Treg cells, and TRM cells. The imbalance of the immune cells in the microenvironment, at least in part, may help to explain how chronic inflammation contributes to EBV‐positive diffuse large B‐cell lymphoma.

Optical enhancement cavities enabling laser pulses to be coherently stacked in free space are used in several applications to enhance accessible optical power. In this study, we develop an optical cavity that accumulates harmonically mode-locked laser pulses with a self-resonating mechanism for X-ray sources based on laser-Compton scattering. In particular, a Fabry-Perot cavity composed of 99% reflectance mirrors maintained the optical resonance in a feedback-free fashion for more than half an hour and automatically resumed the accumulation even if the laser oscillation was suspended. In contrast to conventional optical enhancement cavity systems with a dedicated feedback controller, this characteristic is highly beneficial in practical applications, such as for laser-Compton scattering X-ray sources. Lastly, upscaling and adoption of the proposed system might improve the operability and equipment use of laser Compton-scattering X-ray sources.

The present study attempted to identify the optimal dilution at which at which the effects of surface reaction-type pre-reacted glass-ionomer (S-PRG) filler eluate on human gingival fibroblasts (HGF) may be safely examined in vitro. S-PRG filler is a material that releases six ions and exerts strong caries-suppressing effects. We prepared S-PRG filler eluate in which S-PRG filler and α-MEM were mixed as a medium for HGF. This eluate contains six ions that are released from S-PRG filler. All cells died in proliferation experiments on HGF using S-PRG filler eluate, which demonstrated that unless S-PRG filler eluate was diluted, the ion concentration was strongly cytotoxic. S-PRG filler eluate diluted by 1/100 or more with the addition of 2% or more of FBS was safe for use. We herein successfully established the optimal dilution of S-PRG filler eluate at which HGF may be safely examined in vitro.

Monochromatic hard X-rays with high brightness are desired for medical applications including Auger therapy. One can generate such X-rays through laser-Compton scattering (LCS) by allowing photons from a compact laser system to interact with electrons accelerated by a compact electron accelerator. In this paper, after a brief description of laser-Compton X-ray sources, a scheme called crab crossing to enhance the X-ray intensity is proposed. The effect of crab crossing is evaluated, and we report our dedicated laser system for the crab crossing LCS research.The luminosity enhancement factor by crab crossing is evaluated. For the electron beam, a rf deflector will be used to generate a tilted electron beam. For the laser system, chirped pulsed amplification is adopted. Yb-doped optical fibers and a Yb:YAG thin-disk is used for the laser gain media.The luminosity enhancement factor by crab crossing is expected to be 3.8 when the crossing angle is 45 degrees. 10mJ pulse energy was achieved by thin-disk regenerative amplifier. The pulse duration after the pulse compressor was about 1.5 ps.We are going to demonstrate the LCS X-ray enhancement by crab crossing of electron beam and laser pulse. The expected enhancement factor is 3.8. We have successfully finished the laser development and the proof-of-principle experiment will be conducted soon.

Background The Postoperative Quality of Recovery Scale (PostopQRS) is a survey-based tool that measures quality of the postoperative recovery in multiple domains over multiple time periods. The purpose of this study is to validate the Japanese version of the PostopQRS. Methods A prospective observational study using bilingual healthy volunteers was conducted in Australia to assess equivalence of the test values between the two languages. To assess the feasibility and discriminant validity of the PostopQRS in a Japanese population, an observational study was conducted on patients undergoing ear-nose-throat and orthopedic surgery in Japan, with measurements performed prior to surgery, 2 h, and 1, 3, and 7 days following surgery. The survey was conducted face-to-face while in hospital and via the telephone following discharge. Results Sixty-eight volunteers participated in the validation study. The scores in the Japanese version were similar to the English version in all domains at all timepoints. In the cognitive domain, there were no differences between the Japanese and English versions for word recall and word generation tasks. For digits forwards and digits backwards the values were skewed to the maximal value, and although significantly different, the absolute difference was n=22) and orthopedic (n=29), were included in the clinical study. Orthopedic patients had a significantly worse recovery profile over time in overall recovery (pp=0.02), nociceptive (p=0.03), and activities of daily living (ADL, pp=0.30) or cognitive domains (p=0.10). Conclusion The Japanese version of the PostopQRS is similar to the English version and was able to discriminate recovery between different surgery disciplines. Trial registration UMIN, UMIN000033268, Registered 6 August 2018.

The standard cosmological model assumes a homogeneous and isotropic universe as the background spacetime on large scales called the cosmological principle. However, some observations suggest the possibility of an inhomogeneous and anisotropic universe at large scales. In this paper, we investigate a model of the universe with random inhomogeneities and anisotropies on very large scales, motivated by the supercurvature dark energy model in Nan et al. [Phys. Rev. D 99, 103512 (2019)]. In this model, the authors introduced a scalar field with $\mathcal{O}(1)$ inhomogeneities on a scale sufficiently larger than the current horizon scale (superhorizon scale), and the potential energy of the scalar field explains the accelerating expansion, with slight deviations from the cosmological principle. We aim at clarifying the theoretical prediction on the large-scale structure (LSS) of the matter component in this model. Based on the work on the superhorizon scale fluctuations (superhorizon mode) presented in Nan and Yamamoto [Phys. Rev. D 105, 063518 (2022)], we derive the equations that the perturbative components to the LSS obey as a generalization of the cosmological perturbations theory, which is solved to find the influence of the dark energy inhomogeneities on the formation of the LSS. Finally, we show that the model can be consistent with observations by comparing the $\sigma_8$ predicted by the numerical solution of the model with the $\sigma_8$ indicated by observations such as Planck and SDSS., Comment: 24 pages, 4 figures

Vibration characteristics of a seated human body exposed to whole-body vibration are important factors in ride comfort of automobiles. In a frequency range below approximately 20 Hz, there are main resonance frequencies of the human body. Therefore many previous studies have discussed the vibration characteristics in this frequency range. However, it is necessary to focus on high-frequency vibration because recent development in vibration reduction technology of automobiles reduces low-frequency vibration and occupants can perceive high-frequency vibration. The purpose of this study is to examine the vibration characteristics of the seated human body in a frequency range below 50 Hz. For the purpose, vibration experiments for the human body with a shaking table were conducted. Subjects sat on a rigid seat fixed on the shaking table and were exposed to vertical vibration. Acceleration on the head and several positions on the spine was measured, and seat-to-measurement-point acceleration transmissibility was obtained. The modal characteristics were estimated from the measured data of the transmissibility by using multi-reference iterative curve fitting technique. Five modes were estimated below 50 Hz. The first, second, and third modes were in the frequency range below 20 Hz. The fourth and fifth modes were in a frequency range from 20 Hz to 50 Hz. The modal characteristics, which are a mode shape and a natural frequency, in the high-frequency range varied depending on the subjects, though the modal characteristics in the low-frequency range were almost the same regardless of the subjects.

The present study attempted to identify the optimal dilution at which at which the effects of surface reaction-type pre-reacted glass-ionomer (S-PRG) filler eluate on human gingival fibroblasts (HGF) may be safely examined in vitro. S-PRG filler is a material that releases six ions and exerts strong caries-suppressing effects. We prepared S-PRG filler eluate in which S-PRG filler and α-MEM were mixed as a medium for HGF. This eluate contains six ions that are released from S-PRG filler. All cells died in proliferation experiments on HGF using S-PRG filler eluate, which demonstrated that unless S-PRG filler eluate was diluted, the ion concentration was strongly cytotoxic. S-PRG filler eluate diluted by 1/100 or more with the addition of 2% or more of FBS was safe for use. We herein successfully established the optimal dilution of S-PRG filler eluate at which HGF may be safely examined in vitro.

X-ray enhancement by the crab crossing of electrons and laser photons in laser-Compton scattering (LCS) is studied. Current status of our crab crossing LCS experiment and the development of thin-disk regenerative amplifier is reported.

We investigated the incidence of thromboembolism in patients receiving combination chemotherapy with bevacizumab (BV)for colorectal cancer and examined its association with clinical factors. Between July 2007 and April 2014, 250 patients with colorectal cancer received combination chemotherapy with BV. Thromboembolism occurred in 24 cases(9.6%). Five predictive risk factors(platelet count B350,000/µL, hemoglobin10 g/dL, leukocyte count11,000/mL, body mass index B25.3 kg/m2, and D-dimer B1.44 µg/mL)were set based on a previous report, and the corresponding number of risk factors for thromboembolism and incidence of thromboembolism were examined. The results of multivariate analysis showed that the occurrence of 3 or more risk factors conferred a significant risk for the incidence of thromboembolism. Due to the increased risk of developing thromboembolism in such patients, special attention during management is required.

In this paper, we propose a new interaction technique for controlling applications by touching the forehead that the skin deformation is detected by an enhanced Head-Mounted Display (HMD). This technique envisions supporting commands and controls for applications as map applications and photo viewers without carrying additional controlling device which removes the user’s eye from the display. In this technique, the skin deformation is measured by attaching light sensors to the HMD. The deformation of the skin is caused by the user touching the forehead with the finger. In this paper, we support the recognition of multiple gestures with a Support Vector Machine (SVM).

The conserved U54 in tRNA is often modified to 5-methyluridine (m(5)U) and forms a reverse Hoogsteen base pair with A58 that stabilizes the L-shaped tRNA structure. In Gram-positive and some Gram-negative eubacteria, m(5)U54 is produced by folate/FAD-dependent tRNA (m(5)U54) methyltransferase (TrmFO). TrmFO utilizes N(5),N(10)-methylenetetrahydrofolate (CH(2)THF) as a methyl donor. We previously reported an in vitro TrmFO assay system, in which unstable [(14)C]CH(2)THF was supplied from [(14)C]serine and tetrahydrofolate by serine hydroxymethyltransferase. In the current study, we have improved the TrmFO assay system by optimization of enzyme and substrate concentrations and introduction of a filter assay system. Using this assay, we have focused on the tRNA recognition mechanism of TrmFO. 42 tRNA mutant variants were prepared, and experiments with truncated tRNA and microhelix RNAs revealed that the minimum requirement of TrmFO exists in the T-arm structure. The positive determinants for TrmFO were found to be the U54U55C56 sequence and G53-C61 base pair. The gel mobility shift assay and fluorescence quenching showed that the affinity of TrmFO for tRNA in the initial binding process is weak. The inhibition experiments showed that the methylated tRNA is released before the structural change process. Furthermore, we found that A38 prevents incorrect methylation of U32 in the anticodon loop. Moreover, the m(1)A58 modification clearly accelerates the TrmFO reaction, suggesting a synergistic effect of the m(5)U54, m(1)A58, and s(2)U54 modifications on m(5)s(2)U54 formation in Thermus thermophilus cells. The docking model of TrmFO and the T-arm showed that the G53-C61 base pair is not able to directly contact the enzyme.

For near infrared red spectroscopy (NIRS), the debate over the reliability of its absolute value is ongoing, and discussed in this paper with alpha-blocking task. The purpose of the study is step by step clarification on NIRS reliability. The method in this paper is the evaluation with a task that is clinically important and has achieved a wide consensus and a diagnostics of its measurement. From this viewpoint, this paper discussed the NIRS measurement, with the electroencephalography (EEG) measurement of alpha-blocking as the task. Based on the EEG measurement results of alpha-blocking, we investigated the characteristic changes in the NIRS measurements; a correlation between the two measurements was found (0.806), based on alpha-rhythm patterns of EEG and the increasing or decreasing patterns of oxygen metabolism on NIRS. In addition, a correlation was found between complexities in the two measurements (0.677). The variation level of the complexity in the EEG measurements was 7.14 times larger compared with that of NIRS on average which suggests that the EEG measurements included much information than the NIRS measurements for alpha-blocking task. Despite, the correlation results suggest a possibility of NIRS application to alpha-blocking diagnosis. These numericals contribute to step by step clarification on NIRS reliability.

Antigen binding to B cell receptor (BCR) of pre-mature B lymphocytes leads to their apoptosis, while binding to BCR of mature B lymphocytes induces their activation and proliferation. The former binding is believed to be a mechanism so as to exclude B cell clones leading to protection from auto-immune diseases. Cross-linking of BCR of pre-mature B cells, including chicken DT40 cells, with anti-immunoglobulin antibody induces their apoptosis. The PMA/ionomycin treatments, which mimic BCR stimulation, are used to study intracellular signal transduction of B lymphocytes. Here, by analyzing the Aiolos-deficient DT40 cell line, Aiolos −/− , we reveal that the lack of Aiolos accelerates apoptosis of DT40 cells mediated by BCR signaling. Moreover, the Aiolos-deficiency and BCR signaling cooperatively control this apoptosis through dramatically elevated cytochrome c release from mitochondria to cytosol and elevated caspase (caspase-3, 8 and 9) activities, resulting in drastically diminished amounts of ICAD followed by increased DNA fragmentation. Re-expression study reveals that the shorter isoform of Aiolos (Aio-2) controls PMA/ionomycin-mediated apoptosis via up-regulation and down-regulation of the PKCδ and bak genes, respectively. These findings could be a powerful trigger to resolve molecular mechanisms of negative selection of B lymphocytes and also auto-immune diseases.

tRNAs from all 3 phylogenetic domains have a 5-methyluridine at position 54 (T54) in the T-loop. The methyl group is transferred from S -adenosylmethionine by TrmA methyltransferase in most Gram-negative bacteria and some archaea and eukaryotes, whereas it is transferred from 5,10-methylenetetrahydrofolate (MTHF) by TrmFO, a folate/FAD-dependent methyltransferase, in most Gram-positive bacteria and some Gram-negative bacteria. However, the catalytic mechanism remains unclear, because the crystal structure of TrmFO has not been solved. Here, we report the crystal structures of Thermus thermophilus TrmFO in its free form, tetrahydrofolate (THF)-bound form, and glutathione-bound form at 2.1-, 1.6-, and 1.05-Å resolutions, respectively. TrmFO consists of an FAD-binding domain and an insertion domain, which both share structural similarity with those of GidA, an enzyme involved in the 5-carboxymethylaminomethylation of U34 of some tRNAs. However, the overall structures of TrmFO and GidA are basically different because of their distinct domain orientations, which are consistent with their respective functional specificities. In the THF complex, the pteridin ring of THF is sandwiched between the flavin ring of FAD and the imidazole ring of a His residue. This structure provides a snapshot of the folate/FAD-dependent methyl transfer, suggesting that the transferring methylene group of MTHF is located close to the redox-active N5 atom of FAD. Furthermore, we established an in vitro system to measure the methylation activity. Our TrmFO-tRNA docking model, in combination with mutational analyses, suggests a catalytic mechanism, in which the methylene of MTHF is directly transferred onto U54, and then the exocyclic methylene of U54 is reduced by FADH 2 .

Antigen binding to the B-cell receptor (BCR) of pre-mature B lymphocytes induces their apoptotic cell death, but binding to the BCR of mature B lymphocytes triggers activation and proliferation. Binding to pre-mature B lymphocytes is thought not only to function as a mechanism to exclude B-cell clones that possess the ability to react with self-antigen, but also to act as a defense mechanism in auto-immune diseases. Cross-linking of BCR of pre-mature B-cell lines, including the chicken DT40 cell line, with anti-immunoglobulin IgG induces apoptotic cell death. Treatment with phorbol 12-myristate 13-acetate/ionomycin, which mimics BCR stimulation, is used to study intracellular signal transduction of B lymphocytes. Here, by analyzing the E2A-deficient DT40 cell line, E2A(-/-), we show that E2A deficiency prevents certain levels of apoptotic cell death mediated by BCR signaling. In addition, E2A deficiency-linked BCR signaling controls the mimicked pre-mature B-cell apoptosis by PMA/ionomycin through elevated survivin plus inhibitor of apoptosis 2 levels, and reduced caspase-3 and caspase-8 activities, resulting in increased amounts of ICAD (inhibitor of caspase-activated DNase), compared with those in the presence of E2A, followed by reduction of DNA fragmentation. These findings will contribute to the resolution of molecular mechanisms of negative selection of B cells and also auto-immune diseases.

In this study, we investigated the clinical factors associated with acute kidney injury (AKI) due to combination therapy with cisplatin (CDDP) for treating lung cancer. We classified cases according to the presence or absence of adequate hydration and magnesium(Mg)administered above the regulations of the registered regimen to evaluate the effect due to differences in hydration on AKI. We also investigated clinical factors before and after administration of CDDP in each case group, and examined their association with AKI. Seventy-four patients with lung cancer that were indicated for treatment with a CDDP combination regimen between December 2012 and April 2013 were studied. The patients whose conditions progressed to AKI of Bgrade 2 accounted for 0% (0/33) in the Mg administration group and 7.3%(3/41)in the Mg non-administration group. In particular, 2 cases of serious AKI (grade 4) were observed in the Mg non-administration without additional hydration group. When compared with other groups, a high antiemetic rate and favorable urine volume were observed in the Mg administration with additional hydration group. In the patients with AKI, many developed hyponatremia of Bgrade 3 within 1 week after administration of CDDP. Although Mg administration and ample hydration seem to be effective measures to deal with CDDP-caused AKI, comprehensive monitoring, including antiemesis therapy, after CDDP administration and correction of electrolytes is important.

It is well known that dopamine (DA) modulates, via D"1 receptors, the activity of the dorsolateral prefrontal cortex (DLPFC) for working memory in monkey with an inverted-U shape profile. The activity of the DLPFC is moderate and D"1 receptors in the DLPFC are activated rather modestly. We studied the circuit dynamics of the DLPFC for wider variation of the cortical extracellular DA concentration than usually considered. The model we used for the analysis and the simulation has simple network architecture, consisting of a pyramidal neuron unit and an inhibitory interneuron unit that are reciprocally connected. Nevertheless, the network dynamics shows an interesting and unpredictable behavior in the hyperdopaminergic region. In this region, the simulation shows the emergence of a new mode of the activity, which is characterized by the hyperactivity of the DLPFC and the hyperactivation of the D"1 receptors. This mode of activity shows a marked contrast to the conventional activity mode in the inverted-U region. We term this new mode the 'H mode'. In this study, we characterize the H mode and argue its relevance to psychopathology.

Our on going studies have sought to simulate circuit properties of the mesocortical dopaminergic system. This article describes a reduced model which elucidates the essential nature of dopaminergic modulation in the prefrontal cortex (PFC). Simulating a delayed-response task, we observed that the delay-period activity of the model neurons follows an inverted-U-shaped curve according to the increase in the dopamine level. Subsequent analysis showed that the inverted-U-shaped activation of the model PFC neurons derives from a supercritical pitchfork bifurcation, the formation of which requires synergism between the modulation of the pyramidal-interneuron connection and that of the interneuron's excitability.

We have developed a computational model of the PFC circuit that incorporates dopamine effects via Dl receptor activation. The computer simulation with this model shows an inverted-U shaped concentration-dependent effect of dopamine on the delay-period activity, which is consistent with the experimental result (Nature 376 (1995) 572). The activities of the pyramidal cells (both the baseline and the signal components) are suppressed in high Dl receptor activation levels. The simulation suggests that this is due to feedforward inhibition when the decrement of the AMPA-type currents is weak enough. When it is stronger, however, recurrent inhibition dominates the inhibition.

症例は44歳の卵巣癌再発例で, 4年前病期IIcにて子宮全摘, 付属器摘除, 大網切除をうけている.術後化学療法をうけたが骨盤内再発をきたした. 腫瘍は約3.5cmの大きさで右寄りの第2仙骨下端から尾側にあり, 直腸と仙骨への浸潤が疑われた. 手術は背臥位で左下下腹神経を温存しながら直腸切離, ついでジャックナイフ体位にし第2第3仙骨の間から尾側の仙骨右側半分を切断, 再度背臥位に戻し低位前方切除を施行した. 術後, 一過性に残尿率増加をみたが1か月後は正常化し, 2年半の間再発兆候なく良好なQOLを得ている.

The title alkyne-titanium complexes, prepared from propargyl ethers, Ti(O- i -Pr) 4 and i -PrMgCl, reacted with 2,3- O -isopropylideneglyceraldehyde in good to excellent diastereoselectivities of up to 94:6 to afford the anti -adducts, which are useful precursor for the preparation of optically active polyhydroxy compounds.

Diisopropoxytitanium-propargyl ether complexes 2, readily generated in situ from Ti(OPr i ) 4 2 i PrMgBr reagent and propargylic ethers 3, react with aldehydes and ketones highly regioselectively at the carbon having an α-alkoxyalkyl group, thus affording an efficient and practical method for synthesizing allylic alcohols 4 having an α-alkoxyalkyl group at the β-position. The synthesis of conjugated dienes 7h and 8h from the resulting 4h is also described.

Chiral titanium–alkyne complexes derived from chlorotris[(–)-menthoxy]titanium/2 PriMgCl and alkynes react with aldehydes to afford optically active allylic alcohols in up to 38% ee.

Diisopropoxytitanium-propargyl ether complexes 2, readily generated in situ from Ti(OPr i ) 4 2 i PrMgBr reagent and propargylic ethers 3, react with aldehydes and ketones highly regioselectively at the carbon having an α-alkoxyalkyl group, thus affording an efficient and practical method for synthesizing allylic alcohols 4 having an α-alkoxyalkyl group at the β-position. The synthesis of conjugated dienes 7h and 8h from the resulting 4h is also described.

We previously reported that histone deacetylase-2 (HDAC2) controls the amount of IgM H-chain at the steps of transcription of its gene and alternative processing of its pre-mRNA in DT40 cells. Here, we showed not only that the HDAC2-deficiency caused repressions of gene expressions for HDAC7, EBF1, Pax5, Aiolos and Ikaros, and elevations of gene expressions for HDAC4, HDAC5, PCAF and E2A, but also that it caused altered acetylation levels of several Lys residues of core histones. Using gene targeting techniques, we generated three homozygous DT40 mutants: EBF1(-/-), Aiolos(-/-) and E2A(-/-), devoid of EBF1, Aiolos and E2A genes, respectively. Semiquantitative RT-PCR analysis of the resultant mutants revealed not only that EBF1 and Aiolos down-regulate expressions of IgM H- and L-chain genes, but also that E2A up-regulates expressions of these two genes. These results, together with others, indicate that HDAC2 controls indirectly expressions of IgM H- and L-chain genes through opposite transcriptional regulations of EBF1, Pax5, Aiolos plus Ikaros and E2A genes.

Chiral titanium–alkyne complexes derived from chlorotris[(–)-menthoxy]titanium/2 PriMgCl and alkynes react with aldehydes to afford optically active allylic alcohols in up to 38% ee.