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Since the early 2000s, many types of positron emission tomography (PET) scanners dedicated to breast imaging for the diagnosis of breast cancer have been introduced. However, conventional performance evaluation methods developed for whole-body PET scanners cannot be used for such devices. In this study, we developed phantom tools for evaluating the quantitative accuracy of positron emission mammography (PEM) and dedicated-breast PET (dbPET) scanners using novel traceable point-like

A novel traceable point-like 68Ge/68Ga source was developed for calibration of positron emission tomography (PET) scanners. The source was equipped with a spherically symmetric acrylic positron absorber. The physical characteristics of photons emitted from the point-like source were evaluated by Monte Carlo simulation, considering possible geometrical uncertainties. The calibration factor of a clinical PET/CT scanner was evaluated using four manufactured point-like sources as a practical application of the point-like source. The results were consistent with that determined by the conventional cross-calibration method. The traceable point-like 68Ge/68Ga source is expected to be a simple and practical tool for determining the calibration factor and evaluating the physical characteristics of PET scanners.

Studies carried out to further develop tin-catalyzed trans­carbamoylation reactions demonstrated that transcarbamoylation of cinnamyl alcohol in the context of allyl cyanate-to-isocyanate rearrangement can be efficiently carried out on a ten-gram scale and that tin-­catalyzed transcarbamoylation is a valuable alternative to the method using trichloroacetyl isocyanate. In addition, methyl carbamate was found to be an economical carabamoyl donor in tin-catalyzed transcarbamoylation, which showed broad functional group tolerance and allowed a streamlined workup procedure. Finally, a unique synthetic method was developed for the preparation of carbamate-tethered terpene glycoconjugates.

X-ray and gamma-ray photons are widely used for imaging but require a mathematical reconstruction step, known as tomography, to produce cross-sectional images from the measured data. Theoretically, the back-to-back annihilation photons produced by positron–electron annihilation can be directly localized in three-dimensional space using time-of-flight information without tomographic reconstruction; however, this has not yet been demonstrated due to the insufficient timing performance of available radiation detectors. Here we develop techniques based on detecting prompt Cherenkov photons, which, when combined with a convolutional neural network for timing estimation, resulted in an average timing precision of 32 ps, corresponding to a spatial precision of 4.8 mm. We show this is sufficient to produce cross-sectional images of a positron-emitting radionuclide directly from the detected coincident annihilation photons, without using any tomographic reconstruction algorithm. The reconstruction-free imaging demonstrated here directly localizes positron emission and frees the design of an imaging system from the geometric and sampling constraints that are normally present for tomographic reconstruction. Positron emission imaging without tomographic reconstruction is demonstrated. A Cherenkov radiation detector detects gamma rays produced by positron–electron annihilation. The position of a positron source is determined with a precision of 4.8 mm.

Coincidence time resolution (CTR) of 10 ps is an ultimate goal toward reconstruction-less positron emission tomography (PET). One of the ways to enhance the timing performance of the PET detector is to make use of Cherenkov photons which is promptly emitted on the order of picosecond. A Cherenkov detector composed of a Cherenkov radiator and a fast photo-detector, such as a microchannel plate photomultiplier tube (MCP-PMT) can reach the CTR better than 100 ps full width at half maximum (FWHM). Previously, we have developed the Cherenkov detector where the Cherenkov radiator is integrated with the MCP-PMT to enhance the timing performance, and the CTR of 41.9 ps FWHM was obtained. In this study, we performed two types of experiments; (1) increasing statistics roughly ten times larger than the previous study to precisely determine the timing performance of the detector, (2) stepping a 22Na point source and validating transitions of timing histograms according to the source positions. As a result, the CTR of 41.7 ps FWHM was obtained. Moreover, the CTR between the radiator and the MCP direct interaction was also investigated and approximately 55 ps FWHM was obtained. The transitions of the timing histograms according to the source positions were successfully observed. Finally, we show physical components affecting the CTR and potential capability toward the ultimate goal of 10 ps CTR is discussed.

With the upgradation of detector components, such as scintillators and photodetectors , the PET-image signal-to-noise ratio of time-of-flight positron emission tomography (TOF-PET) systems has been improved, compared to those of ordinary nonTOF-PET systems. A TOF-PET with an ultrahigh time resolution, for example a coincidence time resolution (CTR) better than few tens of picoseconds, can not only improve the image quality, but also remove the image reconstruction process, significantly impacting medical imaging. Therefore, it is crucial to develop a high-time resolution PET detector. We focus on the prompt emission of Cherenkov radiation , owing to the instantaneousness of which, a high time resolution can be expected. One of the candidates for the Cherenkov radiator is lead fluoride (PbF 2 ) due it has excellent properties, including transparency toward the ultraviolet region, high refractive index (n = 1.82), and high density (7.77 g/cm 3). Moreover, it does not contain radioisotopes, unlike lutetium-based scintillators, which are commonly used in the currently available TOF-PET detectors. In this work, we experimentally investigate the timing performance of PbF2-based Cherenkov detectors, breaking down the timing performance into physical components. 3 × 3 × 5 mm3 and 9.6 × 9 . 6 × 5 mm3 PbF2 crystals are used as Cherenkov radiators; both are attached to a microchannel plate photomultiplier tube (MCP-PMT) because the single channel MCP-PMT is one of the best photodetectors in terms of the SPTR, which is 25 ps full width at half maximum (FWHM). All the surfaces, except the end surface where the MCP-PMT is connected, are wrapped in black tape to suppress the reflections of the Cherenkov photons in the crystal. The CTR is measured by placing a detector pair face-to-face, using an 22 Na point source, and an oscilloscope at 20 GS/s with a set bandwidth of 4.2 GHz. A CTR of 46.9 ps FWHM, corresponding to a position resolution of 7.0 mm, is obtained, consistent with our simulation results.

We performed expression and functional analysis of mouse CREB3 regulatory factor (CREBRF) in Neuro2a cells by constructing several expression vectors. Overexpressed full-length CREBRF protein was stabilized by MG132; however, the intrinsic CREBRF expression in Neuro2a cells was negligible under all conditions. On the other hand, N- or C-terminal deletion of CREBRF influenced its stability. Cotransfection of CREBRF together with GAL4-tagged full-length CREB3 increased luciferase reporter activity, and only the N-terminal region of CREBRF was sufficient to potentiate luciferase activity. Furthermore, this positive effect of CREBRF was also observed in cells expressing GAL4-tagged cleaved CREB3, although CREBRF hardly influenced the protein stability of NanoLuc-tagged cleaved CREB3 or intracellular localization of EGFP-tagged one. In conclusion, this study suggests that CREBRF, a quite unstable proteasome substrate, positively regulates the CREB3 pathway, which is distinct from the canonical ER stress pathway in Neuro2a cells.

We have measured, for the first time, the inclusive missing-mass spectrum of the $^{12}$C$(K^-, p)$ reaction at an incident kaon momentum of 1.8 GeV/$c$ at the J-PARC K1.8 beamline. We observed a prominent quasi-elastic peak ($K^-p \rightarrow K^-p$) in this spectrum. In the quasi-elastic peak region, the effect of secondary interaction is apparently observed as a peak shift, and the peak exhibits a tail in the bound region. We compared the spectrum with a theoretical calculation based on the Green’s function method by assuming different values of the parameters for the $\bar{K}$–nucleus optical potential. We found that the spectrum shape in the binding-energy region $-300 \, \text{MeV} < B_{K} < 40$ MeV is best reproduced with the potential depths $V_0 = -80$ MeV (real part) and $W_0 = -40$ MeV (imaginary part). On the other hand, we observed a significant event excess in the deeply bound region around $B_{K} \sim 100$ MeV, where the major decay channel of $K^- NN \to \pi\Sigma N$ is energetically closed, and the non-mesonic decay modes ($K^- NN \to \Lambda N$ and $\Sigma N$) should mainly contribute. The enhancement is fitted well by a Breit–Wigner function with a kaon-binding energy of 90 MeV and width 100 MeV. A possible interpretation is a deeply bound state of a $Y^{*}$-nucleus system.

Brefeldin A (BFA) disrupts the structure of the Golgi apparatus to trigger ER stress signaling pathways. On the other hand, treatment with BFA induces the activation of CREB3, the protein structure of which is similar to that of ATF6. In this study, we established Neuro2a cells in which three different transcription factors, namely, ATF4, ATF3 and CREB3, were deficient using the CRISPR/Cas9 approach, and we investigated the BFA-induced ER and Golgi stress response in these cells. BFA treatment rapidly induced ATF4, ATF3, Herp and GADD153 protein expression in Neuro2a cells. ATF4-deficient Neuro2a cells exhibited significantly decreased mRNA and protein expression of ATF3 and Herp but not GADD153; however, cells deficient in ATF3 exhibited minimal effects on GADD34, GADD153 and Herp expression. The cleavage of CREB3 in Neuro2a cells was triggered by BFA; however, the expression of several ER and Golgi stress-related factors was hardly influenced by the CREB3 deficiency in these Neuro2a cells. This study shows that CREB3 minimally associates with typical ER stress-inducible responses in Neuro2a cells. Therefore, identification and characterization of the downstream transcriptional targets of CREB3 is required to clarify not only Golgi stress response but also its relationship with ER stress signaling pathways.

In order to achieve the ultimate goal of reducing coincidence time resolution (CTR) to 10 ps, thus enabling reconstruction-less positron emission tomography, a Cherenkov-radiator-integrated microchannel plate photomultiplier tube (CRI) reaching CTR of sub-50 ps full width at half maximum (FWHM) has been developed. However, a histogram of time differences between a pair of the CRIs shows undesirable side peaks, which are caused by gamma rays directly interacting with the micro channel plates (MCPs). Such direct interaction events are detrimental to the timing performance of the CRI. In this paper, we demonstrate an analytical method of deconvolving MCP direct interaction events from the timing histogram. Considering the information of the main and the two side peaks, the timing uncertainty caused by the MCP direct interaction events is deconvolved and the CTR of the CRI is analytically investigated. Consequently, the CTR is improved from 41.7 to 40.5 ps FWHM by the deconvolution. It means that a mixture of the Cherenkov radiator events and the MCP direct interaction events contribute to the CTR by a factor of 10 ps. The timing performance of the MCP direct interaction events are also evaluated. The CTR between the two MCPs is found to be 66.2 ps FWHM. This indicates that a photocathode-free radiation detector with high timing performance is possible. Elimination of the photocathode from the detector would make detector construction easier and more robust.

A novel traceable point-like

Aim Cardiopulmonary resuscitation is vital for survival after cardiac arrest, and chest compressions are an important aspect of this. When performing chest compression in a hospital setting, the rescuer often has to kneel on the bed to overcome inconvenient differences in height between the rescuer and the bed. However, as yet no study has evaluated the quality of chest compressions in this position. The aim of this study was to examine the impact on the quality of chest compressions while kneeling on the bed. Methods Fifteen female students performed 2‐min chest compressions on a manikin placed on the floor and a bed. Measurement parameters included compression depth, heart rate, integrated electromyogram, and a visual analog scale. The parameters were measured every 30 s and were statistically compared between the conditions. Results Compression depth at 30, 60, 90, and 120 s differed significantly between the conditions. Heart rate values at 150 and 210 s of recovery significantly differed between the conditions. Integrated electromyogram values for the trapezius, rectus femoris, and biceps femoris differed between the floor and bed conditions during 2‐min chest compressions, whereas the external oblique muscle significantly differed at 60 and 120 s. Visual analog scales for fatigue, effectiveness, and stability significantly differed between the conditions. Conclusion Kneeling on the bed does not enable grounding of the toe, causing the upper body to be unstable and limiting generation of the power required for chest compression. Our results suggest that rotation every minute is necessary to maintain effective cardiopulmonary resuscitation while kneeling on the bed.

In the K1.8 beam-line at Hadron Experimental Facility of J-PARC, a new magnetic spectrometer S-2S is being installed. S-2S was designed to achieve a high momentum resolution of Δp/p = 6 × 10−4 in FWHM. Several strangeness-physics programs which require the high resolution will be realized by S-2S. The present article introduces J-PARC E70 (missing-mass spectroscopy of Ξ12Be) and E94 (missing-mass spectroscopy of Λ7Li, Λ10B, and Λ12C) experiments.

Purpose Cherenkov radiation has recently received attention due to its prompt emission phenomenon, which has the potential to improve the timing performance of radiation detectors dedicated to positron emission tomography (PET). In this study, a Cherenkov-based three-dimensional (3D) position-sensitive radiation detector was proposed, which is composed of a monolithic lead fluoride (PbF2 ) crystal and a photodetector array of which the signals can be readout independently. Methods Monte Carlo simulations were performed to estimate the performance of the proposed detector. The position- and time resolution were evaluated under various practical conditions. The radiator size and various properties of the photodetector, e.g., readout pitch and single photon timing resolution (SPTR), were parameterized. The single photon time response of the photodetector was assumed to be a single Gaussian for the simplification. The photo detection efficiency of the photodetector was ideally 100% for all wavelengths. Compton scattering was included in simulations, but partly analyzed. To estimate the position at which a γ-ray interacted in the Cherenkov radiator, the center-of-gravity (COG) method was employed. In addition, to estimate the depth-of-interaction (DOI) principal component analysis (PCA), which is a multivariate analysis method and has been used to identify the patterns in data, was employed. The time-space distribution of Cherenkov photons was quantified to perform PCA. To evaluate coincidence time resolution (CTR), the time difference of two independent γ-ray events was calculated. The detection time was defined as the first photon time after the SPTR of the photodetector was taken into account. Results The position resolution on the photodetector plane could be estimated with high accuracy, by using a small number of Cherenkov photons. Moreover, PCA showed an ability to estimate the DOI. The position resolution heavily depends on the pitch of the photodetector array and the radiator thickness. If the readout pitch were ideally 0 and practically 3 mm, a full-width at half-maximum (FWHM) of 0.348 and 1.92 mm was achievable with a 10-mm-thick PbF2 crystal, respectively. Furthermore, first-order correlation could be observed between the primary principal component and the true DOI. To obtain a coincidence timing resolution better than 100-ps FWHM with a 20-mm-thick PbF2 crystal, a photodetector with SPTR of better than σ = 30 ps was necessary. Conclusions From these results, the improvement of SPTR allows us to achieve CTR better than 100-ps FWHM, even in the case where a 20-mm-thick radiator is used. Our proposed detector has the potential to estimate the 3D interaction position of γ-rays in the radiator, using only time and space information of Cherenkov photons.

Genetic variability in Plasmodium falciparum malaria parasites hampers current malaria vaccine development efforts. Here, we hypothesize that to address the impact of genetic variability on vaccine efficacy in clinical trials, conserved antigen targets should be selected to achieve robust host immunity across multiple falciparum strains. Therefore, suitable vaccine antigens should be assessed for levels of polymorphism and genetic diversity. Using a total of one hundred and two clinical isolates from a region of high malaria transmission in Uganda, we analyzed extent of polymorphism and genetic diversity in four recently reported novel blood-stage malaria vaccine candidate proteins: Rh5 interacting protein (PfRipr), GPI anchored micronemal antigen (PfGAMA), rhoptry-associated leucine zipper-like protein 1 (PfRALP1) and Duffy binding-like merozoite surface protein 1 (PfMSPDBL1). In addition, utilizing the wheat germ cell-free system, we expressed recombinant proteins for the four candidates based on P. falciparum laboratory strain 3D7 sequences, immunized rabbits to obtain specific antibodies (Abs) and performed functional growth inhibition assay (GIA). The GIA activity of the raised Abs was demonstrated using both homologous 3D7 and heterologous FVO strains in vitro. Both pfripr and pfralp1 are less polymorphic but the latter is comparatively more diverse, with varied number of regions having insertions and deletions, asparagine and 6-mer repeats in the coding sequences. Pfgama and pfmspdbl1 are polymorphic and genetically diverse among the isolates with antibodies against the 3D7-based recombinant PfGAMA and PfMSPDBL1 inhibiting merozoite invasion only in the 3D7 but not FVO strain. Moreover, although Abs against the 3D7-based recombinant PfRipr and PfRALP1 proteins potently inhibited merozoite invasion of both 3D7 and FVO, the GIA activity of anti-PfRipr was much higher than that of anti-PfRALP1. Thus, PfRipr is regarded as a promising blood-stage vaccine candidate for next-generation vaccines against P. falciparum.

Background To investigate the potential prognostic value of image analysis of pelvic bone metastasis in newly diagnosed prostate cancer patients.Methods Data from 69 patients with both bone scintigraphy and pelvic CT images were selected for this analysis. Open source software (3D Slicer version 4.8.1.) was used for image analysis. Metastatic pelvic bone lesions were manually contoured, and radiomic features were extracted. As risk factors for overall survival (OS) and cause-specific survival (CSS), 105 radiomic features and clinical risk factors including age, initial prostate-specific antigen, Gleason score, TNM stage, lactate dehydrogenase (LDH), hemoglobin (Hb), alkaline phosphatase, extent of disease, visceral metastases, castration-resistant prostate cancer (CRPC), and number of systemic agents including abiraterone, enzalutamide, docetaxel and cabazitaxel which CRPC patients received were assessed by uni- and multivariate analyses.Results Median follow-up was 41 months (range, 0-157 months). Three- and 5-year overall survival rates were 66.6% and 37.9%, respectively. Three- and 5-year cause-specific survival rates were 69.4% and 43.5%, respectively. After multivariate analysis, LDH, Hb, and “maximum 2D diameter” defined as maximum tumor size in the axial plane were detected as risk factors for OS. Gleason sum, LDH, and maximum 2D diameter were detected as risk factors for CSS.Conclusion Maximum 2D diameter of pelvic bone metastasis was detected as a significant prognostic factor for metastatic prostate cancer patients.

We have measured an inclusive missing-mass spectrum of the 12 C(K−, p) reaction over wide energy region at the kaon incident momentum of 1.8 GeV/c at J-PARC K1.8 beam line. This measurement was carried out as a by-product of a pilot run of J-PARC E05 experiment, which searched for the Ξ-hypernuclei via 12C(K−, K+) reaction. We have compared the observed missing-mass spectrum with a DWIA calculation to study the K-nucleus interaction. In this comparison, we have changed the depth of both real and imaginary parts of the optical potential between the K and nucleus. It is found that the observed spectrum is best reproduced by the calculation of the potential depth of V0 ∼ −80 MeV (real part) and W0 ∼ −40 MeV (imaginary part). On the other hand, we have observed a definitive excess around the deeply bound region BK ≳ 100 MeV. The excess cannot be explained by the any optical potential and quasi-free background reaction. It is well fitted with a Breit-Wigner function with a binding energy of 90 MeV and a width of 100 MeV, which can be interpreted as a deeply bound Λ(1405) nucleus.

For the full understanding of baryon-baryon interactions in flavor SU(3), the ΞN interaction is the last missing piece of information. So far, we have revealed the ΛN interaction to be attractive (UΛ ≈ 30 MeV), and ΣN interaction to be repulsive in the medium to heavy mass-number region. The ΛΛ bonding energy is weakly attractive. While we have a few experimental observations suggesting the ΞN interaction would be attractive, there still exist large theoretical ambiguities weather it is attractive or not. Experimental determinations on the existence of bound states of Ξ hypernuclei by observing bound-state peaks are strongly awaited. In this report, a new preliminary result on the missing-mass spectrum of a 12C(K−, K+) reaction, which strongly suggests the existence of Ξ-hypernuclear bound states, is presented.For the full understanding of baryon-baryon interactions in flavor SU(3), the ΞN interaction is the last missing piece of information. So far, we have revealed the ΛN interaction to be attractive (UΛ ≈ 30 MeV), and ΣN interaction to be repulsive in the medium to heavy mass-number region. The ΛΛ bonding energy is weakly attractive. While we have a few experimental observations suggesting the ΞN interaction would be attractive, there still exist large theoretical ambiguities weather it is attractive or not. Experimental determinations on the existence of bound states of Ξ hypernuclei by observing bound-state peaks are strongly awaited. In this report, a new preliminary result on the missing-mass spectrum of a 12C(K−, K+) reaction, which strongly suggests the existence of Ξ-hypernuclear bound states, is presented.

Achieving direct imaging of the annihilation position of a positron on an event-by-event basis using an ultrafast detector would have a great impact on the field of nuclear medicine. Cherenkov emission is the most attractive physical phenomenon for realizing such an ultrafast timing performance. Moreover, a microchannel-plate photomultiplier tube (MCP-PMT) is one of the most promising photodetectors for fully exploiting the fast timing properties of Cherenkov emission owing to its excellent single photon time resolution of 25 ps full width at half maximum (FWHM). However, as the MCP structure generally contains a lead compound, the gamma rays frequently and directly interact with the MCP, resulting in the degradation of its timing performance and generation of undesirable side peaks in its coincidence timing histogram. To overcome this problem, we have developed a new MCP-PMT based on an MCP consisting of borosilicate glass, thus drastically reducing the probability of the photoelectric effect occurring in the MCP. To evaluate its insensitivity to gamma rays and its timing performance, a coincidence experiment was performed and showed that the probability of direct interactions was reduced by a factor of 3.4. Moreover, a coincidence time resolution of 35.4 ± 0.4 ps FWHM, which is equivalent to a position resolution of 5.31 mm, was obtained without any pulse height/area cut, improving to 28.7 ± 3.0 ps when selecting on the highest amplitude events by careful optimization of the voltage divider circuit of the new MCP-PMT. The timing performance of this new MCP-PMT presents an important step toward making direct imaging possible.

To apply deep learning to estimate the three-dimensional interaction position of a Cherenkov detector, an experimental measurement of the true depth of interaction is needed. This requires significant time and effort. Therefore, in this study, we propose a direct annihilation position classification method based on deep learning using paired Cherenkov detectors. The proposed method does not explicitly estimate the interaction position or time-of-flight information and instead directly estimates the annihilation position from the raw data of photon information measured by paired Cherenkov detectors. We validated the feasibility of the proposed method using Monte Carlo simulation data of point sources. A total of 125 point sources were arranged three-dimensionally with 5 mm intervals, and two Cherenkov detectors were placed face-to-face, 50 mm apart. The Cherenkov detector consisted of a monolithic PbF2 crystal with a size of 40 &times, 40 &times, 10 mm3 and a photodetector with a single photon time resolution (SPTR) of 0 to 100 picosecond (ps) and readout pitch of 0 to 10 mm. The proposed method obtained a classification accuracy of 80% and spatial resolution with a root mean square error of less than 1.5 mm when the SPTR was 10 ps and the readout pitch was 3 mm.

A new standardization method for a sealed (22)Na point source was developed utilizing two NaI(Tl) scintillation detectors. In the proposed method, the count rates of annihilation radiation, gamma rays, their coincidence sum, and the coincidences between the two detectors are used. The equations from which the source activity can be deduced are derived in this work. A series of EGS-5 Monte Carlo calculations were conducted to test the validity of the expressions. The calculated activity agreed within approximately 1 percent with the literature data used as input in the simulations.

Radiation detectors dedicated to time-of-flight positron emission tomography (PET) have been developed, and coincidence time resolution (CTR) of sub-100 ps full width at half maximum (FWHM) has been achieved by carefully optimizing scintillators and photodetectors. Achieving a CTR of 30 ps FWHM by using a pair of annihilation γ-rays would allow us to directly localize the annihilation point within an accuracy of 4.5 mm. Such direct localization can potentially eliminate the requirement of image reconstruction processes in clinical PET systems, which would have a huge impact on clinical protocols and molecular imaging. To obtain such a high CTR, researchers have investigated the use of prompt emissions such as Cherenkov radiation and hot-intra band luminescence. Although it is still challenging to achieve a CTR of 30 ps FWHM even with a Cherenkov-based detector, the experimentally measured CTR is approaching the goal. In this work, we developed a Cherenkov-radiator-integrated micro-channel plate photomultiplier tube (CRI-MCP-PMT), where there are no optical boundaries between the radiator and photocathode, and its timing performance was investigated. By removing the optical boundaries, reflections are eliminated and transmission to the photocathode is improved, resulting in high timing capability. As a result, a CTR of 30.1 ± 2.4 ps FWHM, which is equivalent to a position resolution of 4.5 ± 0.3 mm along a line of response (LOR), was obtained by using a pair of CRI-MCP-PMTs.