Background contributions in the electron-tracking Compton camera onboard SMILE-2+

The Mega electron volt (MeV) gamma-ray observation is a promising diagnostic tool for observing the universe. However, the sensitivity of MeV gamma-ray telescopes is limited due to peculiar backgrounds, restricting the application of MeV gamma rays for observation. Identification of backgrounds is crucial for designing next-generation telescopes. Therefore, herein, we assessed the background contribution in the electron-tracking Compton camera (ETCC) on board the SMILE- 2+ balloon experiment. This assessment was performed using the Monte Carlo simulation. The results revealed that the background below 400 keV existed due to the atmospheric gamma-ray background, the cosmic-ray/secondary-particle background, and the accidental background. On the other hand, the unresolved background component, which was not likely to be relevant to direct Compton-scattering events in the ETCC, was confirmed above 400 keV. Overall, this study demonstrated that the Compton-kinematics test provides a powerful tool to remove the background and principally improves the signal-to-noise ratio at 400 keV by an order of magnitude.Comment: 11 pages, 18 figure

Efficient derivation and banking of clinical-grade human embryonic stem cell lines in accordance with Japanese regulations

[Introduction] We recently established clinical-grade human embryonic stem cell (hESC) line KthES11 in accordance with current good manufacturing practice standards in Japan. Despite this success, the establishment efficiency was very low at 7.1% in the first period. [Methods] To establish clinical-grade hESC lines, we used xeno-free chemically defined medium StemFit AK03N with the LM-E8 fragments instead of feeder cells. The protocol was then optimized, especially in the early culture phase. [Results] We established five hESC lines (KthES12, KthES13, KthES14, KthES15, and KthES16) with 45.5% efficiency. All five hESC lines showed typical hESC-like morphology, a normal karyotype, pluripotent state, and differentiation potential for all three germ layers. Furthermore, we developed efficient procedures to prepare master cell stocks for clinical-grade hESC lines and an efficient strategy for quality control testing. [Conclusions] Our master cell stocks of hESC lines may contribute to therapeutic applications using human pluripotent stem cells in Japan and other countries

Development of Convolutional Neural Networks for an Electron-Tracking Compton Camera

Electron-tracking Compton camera, which is a complete Compton camera with tracking Compton scattering electron by a gas micro time projection chamber, is expected to open up MeV gamma-ray astronomy. The technical challenge for achieving several degrees of the point spread function is the precise determination of the electron-recoil direction and the scattering position from track images. We attempted to reconstruct these parameters using convolutional neural networks. Two network models were designed to predict the recoil direction and the scattering position. These models marked 41$~$degrees of the angular resolution and 2.1$~$mm of the position resolution for 75$~$keV electron simulation data in Argon-based gas at 2$~$atm pressure. In addition, the point spread function of ETCC was improved to 15$~$degrees from 22$~$degrees for experimental data of 662$~$keV gamma-ray source. These performances greatly surpassed that using the traditional analysis

Decreased Time on the Nondominant One-Leg Standing Test Associated with Repeated Falls in Older Residents with Healthy Aging, Mild Cognitive Impairment, and Dementia: The Wakuya Project

Introduction: The aim of this study is to clarify the association between repeated falls and the dominant/nondominant side in the open-eyed one-leg standing (OLS) test among people who are healthy or have mild cognitive impairment (MCI) or dementia in a community setting. We recruited 180 participants from 39 areas in the town of Wakuya. Methods: This is a cross-sectional study. Participants were classified into 3 Clinical Dementia Rating (CDR) groups, i.e., CDR 0 (healthy, n = 71), CDR 0.5 (MCI, n = 85), and CDR 1+ (n = 23), and they were investigated for motor function (grip strength, 6-m normal gait speed, timed up and go test, and OLS test) and falls during the past year. Results: Subjects with a CDR of 0.5 had higher rates of single and repeated falls (13.0 and 23.4%, respectively) than the CDR 0 group (12.1 and 4.5%, respectively), as did those in CDR 1+ group (15.0 and 30.0%). For the CDR 0.5 group, the frequency of falls was negatively (biologically meaningful direction) correlated with the left OLS time. No significant correlations with falls were found for other motor function tests. Another analysis separating the CDR 0.5 group into 2 subgroups (repeated falls vs. no or a single fall) also showed that the left OLS time was lower in subjects with repeated falls. Conclusion: People with MCI who had fallen repeatedly in the year before the assessment had a significantly lower left OLS time compared to those who had not fallen or had had 1 fall with MCI. None of the other physical measures were associated with past repeat falls including OLS on the dominant right side. No such findings were noted in the CDR 0 and CDR 0+ groups

Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making

「何を買うんだっけ」と「どれにしよう」を処理する2つの脳回路を明らかに --霊長類の生体脳で神経経路を可視化・操作する技術で解明、高次脳機能の理解へ大きく前進--. 京都大学プレスリリース. 2021-06-24.The primate prefrontal cortex (PFC) is situated at the core of higher brain functions via neural circuits such as those linking the caudate nucleus and mediodorsal thalamus. However, the distinctive roles of these prefronto-subcortical pathways remain elusive. Combining in vivo neuronal projection mapping with chemogenetic synaptic silencing, we reversibly dissected key pathways from dorsolateral part of the PFC (dlPFC) to the dorsal caudate (dCD) and lateral mediodorsal thalamus (MDl) individually in single monkeys. We found that silencing the bilateral dlPFC-MDl projections, but not the dlPFC-dCD projections, impaired performance in a spatial working memory task. Conversely, silencing the unilateral dlPFC-dCD projection, but not the unilateral dlPFC-MDl projection, altered preference in a decision-making task. These results revealed dissociable roles of the prefronto-subcortical pathways in working memory and decision-making, representing the technical advantage of imaging-guided pathway-selective chemogenetic manipulation for dissecting neural circuits underlying cognitive functions in primates

Distribution of polycyclic aromatic hydrocarbons (PAHs) in rivers and estuaries in Malaysia: a widespread input of petrogenic PAHs

This is the first publication on the distribution and sources of polycyclic aromatic hydrocarbons (PAHs) in riverine and coastal sediments in South East Asia where the rapid transfer of land-based pollutants into aquatic environments by heavy rainfall and runoff waters is of great concern. Twenty-nine Malaysian riverine and coastal sediments were analyzed for PAHs (3−7 rings) by gas chromatography mass spectrometry. Total PAHs concentra tions in the sediment ranged from 4 to 924 ng/g. Alkylated homologues were abundant for all sediment samples. The ratio of the sum of methylphenanthrenes to phenanthrene (MP/P), an index of petrogenic PAHs contribution, was more than unity for 26 sediment samples and more than 3 for seven samples for urban rivers covering a broad range of locations. The MP/P ratio showed a strong correlation with the total PAHs concentrations, with an r2 value of 0.74. This ratio and all other compositional features indicated that Malaysian urban sediments are heavily impacted by petrogenic PAHs. This finding is in contrast to other studies reported in many industrialized countries where PAHs are mostly of pyrogenic origin. The MP/P ratio was also significantly correlated with higher molecular weight PAHs such as benzo[a]pyrene, suggesting unique PAHs source in Malaysia which contains both petrogenic PAHs and pyrogenic PAHs. PAHs and hopanes fingerprints indicated that used crankcase oil is one of the major contributors of the sedimentary PAHs. Two major routes of inputs to aquatic environments have been identified:  (1) spillage and dumping of waste crankcase oil and (2) leakage of crankcase oils from vehicles onto road surfaces, with the subsequent washout by street runoff. N-Cyclohexyl-2-benzothiazolamine (NCBA), a molecular marker of street dust, was detected in the polluted sediments. NCBA and other biomarker profiles confirmed our hypothesis of the input from street dust contained the leaked crankcase oil. The fingerprints excluded crude oil, fresh lubricating oil, asphalt, and tire-particles as major contributors

A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO

©2016 Gun-Hee Lee et al. Originally published in Journal of Cell Biology. https://doi.org/10.1083/jcb.20160512

Antitumor effect of WEE1 blockade as monotherapy or in combination with cisplatin in urothelial cancer

Overcoming cisplatin (CDDP) resistance is a major issue in urothelial cancer (UC), in which CDDP-based chemotherapy is the first-line treatment. WEE1, a G2/M checkpoint kinase, confers chemoresistance in response to genotoxic agents. However, the efficacy of WEE1 blockade in UC has not been reported. MK-1775, a WEE1 inhibitor also known as AZD-1775, blocked proliferation of UC cell lines in a dose-dependent manner irrespective of TP53 status. MK-1775 synergized with CDDP to block proliferation, inducing apoptosis and mitotic catastrophe in TP53-mutant UC cells but not in TP53-WT cells. Knocking down TP53 in TP53-WT cells induced synergism of MK-1775 and CDDP. In UMUC3 cell xenografts and two patient-derived xenograft lines with MDM2 overexpression, in which the p53/cell cycle pathway was inactivated, AZD-1775 combined with CDDP suppressed tumor growth inducing both M-phase entry and apoptosis, whereas AZD-1775 alone was as effective as the combination in RT4 cell xenografts. Drug susceptibility assay using an ex vivo cancer tissue-originated spheroid system showed correlations with the in vivo efficacy of AZD-1775 alone or combined with CDDP. We determined the feasibility of the drug susceptibility assay using spheroids established from UC surgical specimens obtained by transurethral resection. In conclusion, WEE1 is a promising therapeutic target in the treatment of UC, and a highly specific small molecule inhibitor is currently in early phase clinical trials for cancer. Differential antitumor efficacy of WEE1 blockade alone or combined with CDDP could exist according to p53/cell cycle pathway activity, which might be predictable using an ex vivo 3D primary culture system