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Thyroid hormone (TH) has long been believed to play a minor role in male reproduction. However, evidences from experimental model of thyrotoxicosis or hypothyroidism suggests its role in spermatogenesis. Cellular action of TH requires membrane transport via specific transporters such as monocarboxylate transporter 8 (MCT8). SLC16A2 (encodes for MCT8) inactivating mutation in humans can lead to Allan-Herndon Dudley-syndrome, a X-linked psychomotor and growth retardation. These patients present cryptorchidism which suggests a role of MCT8 during spermatogenesis. In this study, we found that Mct8 is highly expressed during early postnatal development and decreases its expression in the adulthood of testis of wild-type male rats. Histological analysis revealed that spermatogonia largely lacks MCT8 expression while spermatocytes and maturing spermatids highly express MCT8. To further understand the role of Mct8 during spermatogenesis, we generated Slc16a2 (encodes MCT8) knockout rats using CRISPR/Cas9. Serum THs (T3 and T4) level were significantly altered in Slc16a2 knockout rats when compared to wild-type littermates during early to late postnatal development. Unlike Slc16a2 knockout mice, Slc16a2 knockout rats showed growth delay during early to late postnatal development. In adult Slc16a2 knockout rats, we observed reduced sperm motility and viability. Collectively, our data unveil a functional involvement of MCT8 in spermatogenesis, underscoring the importance of TH signaling and action during spermatogenesis.

For the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), variable neuroimaging and neuropsychological tests have been used. We aimed to evaluate the correlation of neuropsychological domain with new amyloid positron emission tomography (PET) study and to validate the availability of new PET tracer. We enrolled 20 patients who underwent 11C-PiB-PET/CT, new PET tracer 18F-FC119S PET/CT from November, 2014 to July, 2015. Among them, 10 patients were diagnosed with AD and 10 patients with MCI. The current version of Seoul Neuropsychological Screening Battery (SNSB) II was performed for cognitive evaluation. Each parameter of SNSB was compared between 2 patient groups. Spearman correlation analysis between value of SNSB domain and standardized uptake value ratio (SUVR) of PET was also performed. The AD group presented significant poor z-score in Korean-Boston Naming Test(K-BNT) (P = .01),copy score of Rey Complex Figure Test (RCFT) (P = .049), immediate (P = .028)and delayed memory of Seoul Verbal Learning Test (SVLT) (P = .028), recognition of RCFT (P = .004), “animal” of Controlled Oral Word Association Test (COWAT) (P = .041), color reading of Korean-Color Word Stroop test (K-CWST) (P = .014), and Digit Symbol Coding (DSC) (P = .007) compared with MCI group. That means, except attention domain, all other cognitive domains were relatively impaired in AD compared with MCI. In correlation analysis, we found that poor performances on copy score of RCFT in MCI groups were associated with great beta amyloid burden in frontal area in both 11C-PiB-PET/CT and 18F-FC119S PET/CT. In AD group, 18F-FC119S PET presented more extensive correlation in each cognitive domain with multiple cortical areas compared with 11C-PiB-PET. The degree of amyloid burden assessed on 18F-FC119S PET was significantly correlated with neuropsychological test in AD, and also MCI patients. The combination of neuropsychological evaluation with novel 18F-FC119S PET/CT can be used for valid biomarker for MCI and AD.

PURPOSE: This study aimed to construct a database of the effective doses (ED) from F-18 fluorodeoxyglucose (FDG) torso positron emission tomography/computed tomography (PET/CT) in Korea to provide data that supports the reduction of the CT dose of PET/CT and optimization of PET/CT protocols in Korea. METHODS: We investigated data of ED and CT parameters of FDG PET/CT. The data were analyzed by body weight groups. RESULTS: A total of 31 hospitals participated in the survey (99 adults). The mean total EDs (± SD) were 8.77 ± 2.76, 10.93 ± 3.14, and 12.57 ± 3.79 mSv for the 55-, 70-, and 85-kg groups, respectively. The FDG EDs were 4.80 ± 0.98, 6.05 ± 1.15, and 6.89 ± 1.52 mSv, and the CT EDs were 4.00 ± 2.12, 4.88 ± 2.51, and 5.68 ± 2.89 mSv, respectively. Of the enrolled hospitals, 54.5% used ultra-low-dose CT protocols, and their CT ED was significantly lower than low-dose CT group in all groups (2.9 ± 1.0, 3.2 ± 1.1, and 3.3 ± 1.0 mSv vs. 6.6 ± 1.6, 7.2 ± 2.1, and 7.9 ± 2.2 mSv, all p

The study of metabolomics and disease has enabled the discovery of new risk factors, diagnostic markers, and drug targets. For neurological and psychiatric phenotypes, the cerebrospinal fluid (CSF) is of particular importance. However, the CSF metabolome is difficult to study on a large scale due to the relative complexity of the procedure needed to collect the fluid. Here, we present a metabolome-wide association study (MWAS), which uses genetic and metabolomic data to impute metabolites into large samples with genome-wide association summary statistics. We conduct a metabolome-wide, genome-wide association analysis with 338 CSF metabolites, identifying 16 genotype-metabolite associations (metabolite quantitative trait loci, or mQTLs). We then build prediction models for all available CSF metabolites and test for associations with 27 neurological and psychiatric phenotypes, identifying 19 significant CSF metabolite-phenotype associations. Our results demonstrate the feasibility of MWAS to study omic data in scarce sample types., Here, the authors introduce a metabolome-wide association study that combines a genome-wide association study of cerebrospinal fluid metabolites with publicly available genome-wide association study summary statistics of neurological and psychiatric conditions to identify 19 significant CSF metabolite-phenotype associations.

A single-photon-emission computed tomography (SPECT) system with a lanthanum-bromide (LaBr3:Ce) scintillator was proposed and simulated to detect neutron-activated prompt γ-rays from suspicious materials. The optimized parameters of the SPECT system were calculated to achieve the best performance. Under the optimized conditions, energy spectra, spatial images, and elemental ratios were obtained and employed to identify hidden materials. The carbon-to-oxygen ratios of the materials calculated through the simulations were consistent with the corresponding theoretical values while the calculated nitrogen-to-oxygen ratios were slightly different from the corresponding theoretical values. In the proposed system, not only the energy spectrum of each element but also the characteristic intensity ratios obtained using the reconstructed images were used to identify the unknown elements of hidden materials in the three-dimensional spatial domain. These results demonstrate the feasibility of using the SPECT system in field applications.

Interatomic potentials for pure Zn and Mg–Zn binary system have been developed on the basis of the second nearest-neighbor modified embedded-atom method formalism. The potentials describe fundamental material properties of pure Zn (bulk, defect, and thermal properties) reasonably and reproduce the alloy behavior (thermodynamic, structural, and elastic properties of compounds and solution phases) of Mg-Zn alloys well in good agreement with experiments, first-principles and CALPHAD. The applicability of the developed potentials to atom-scale investigations on the slip behavior of Mg-Zn alloys is also demonstrated by showing that the calculated effects of Zn on the general stacking fault energy on the basal, prismatic and pyramidal planes are consistent with first-principles calculations.

A collimator is a key component of gamma cameras, which affects imaging performance significantly. Recently, pixelated scintillator arrays are widely applied in the development of highresolution gamma cameras, instead of monolithic scintillator blocks. Therefore, combining the collimator and the pixelated scintillator has been a crucial factor in achieving good imaging performance. In this study, we investigated the effects of the shape and position of a collimator hole on the image resolution of a gamma camera with a pixelated scintillator. We designed a pixel-matched collimator and a low-energy high-resolution (LEHR) collimator with hexagonal shaped holes that have the same collimator geometrical efficiency. Simulation experiments were performed with a Monte Carlo simulation package (GATE v7.0). For both types of collimator, camera sensitivity was measured for validating the collimator efficiency, and planar images were obtained to measure spatial resolution, with changing the line profile angle based on the septa direction. Camera sensitivities for both collimators were equivalent (difference = 1.76 ± 0.51%). In contrast to the case of the pixel-matched collimator, in the case of the LEHR collimator, as the angle of the line profile varied, the spatial resolution showed a difference at each profile angle. In the case when two collimator holes symmetrically matched with one scintillator pixel, the spatial resolution showed a 64.87% difference in its maximum and a position distortion of 26.06% from the original source position, according to the profile angle, compared to the other unmatched cases. These results showed that using a pixel-matched collimator in gamma camera systems employing a pixelated scintillator is essential for the exact delineation of small regions using high resolution gamma camera imaging

To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (68Ga/64Cu) and therapy (177Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which 177Lu-L1 exhibited markedly higher uptake in HeLa cells than the 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of 68Ga-L1 and 64Cu-L1 was clearly visualized in the tumor site, while 177Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when 68Ga-L1 or 64Cu-L1 is used for diagnosis, 177Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other.

Since Chomsky 1976 , it has been claimed that focus on a referring expression blocks coreference in a cataphoric dependency (* Hisi mother loves JOHNi vs. Hisi mother LOVES Johni ). In three auditory experiments and a written questionnaire, we show that this fact does not hold when a referent is unambiguously established in the discourse (cf. Williams 1997 , Bianchi 2009 ) but does hold otherwise, validating suggestions in Rochemont 1978 , Horvath 1981 , and Rooth 1985 . The perceived effect of prosody, we argue, building on Williams’s original insight and deliberate experimental manipulation of Rochemont’s and Horvath’s examples, is due to the fact that deaccenting the R-expression allows hearers to accommodate a salient referent via a “question under discussion” ( Roberts 1996/2012 , Rooth 1996 ), to which the pronoun can refer in ambiguous or impoverished contexts. This heuristic is not available in the focus cases, and we show that participants’ interpretation of the pronoun is ambivalent here.

To get highly efficient quasi-solid-state dye-sensitized solar cells (QSS-DSSCs) with long-term stability using polymer gel electrolytes (PGEs), well-defined ABA triblock copolymers ([Poly(methyl methacrylate)]2-block-poly(ethylene glycol)) with different end functionality and components of I-/I3- liquid electrolytes (LEs) are studied and optimized for the fabrication of PGE-based QSS-DSSCs. Triblock copolymers are synthesized in a one-step reaction using bifunctional PEG-macro chain transfer agent (MCTA) by reversible addition-fragmentation chain transfer (RAFT) polymerization. Due to the high reactivity and toxicity of sulfur-containing trithiocarbonate end groups, ABA triblock copolymers prepared from RAFT polymerization are further modified to sulfur-free 2-methylpropionitrile and 4-cyanopentanoic acid end functional triblock copolymers by radical-induced exchange reactions. Dodecyl trithiocarbonate end functional PEG-MCTA and triblock copolymers absorb UV-light in the region of 260–380 nm, whereas sulfur-free carboxylic acid and 2-methylpropionitrile end functional polymers do not absorb in that UV-light region. Among three different end functional polymers, the carboxylic acid end functional triblock copolymer has the highest thermal stability. Based on electrochemical parameters, photovoltaic performance, and long-term stability, 1,2-dimethyl-3-propylimidazolium iodide (DMPII) ionic liquid and 4-tert-butylpyridine (TBP) additive containing acetonitrile-based I-/I3- LEs are effective for PGEs. The highest power conversion efficiency (PCE) for QSS-DSSCs achieved under simulated 1-sun illumination is up to 10.34%, which is comparable with the highest PCE of 10.39% for LE-DSSCs. Considering the high reactivity, thermal stability, UV-absorption, and the toxicity of the trithiocarbonate end group, the SGT-643-C triblock copolymer with carboxylic acid end group can be a promising candidate as a sulfur-free polymeric matrix for gel electrolytes of QSS-DSSCs.

To evaluate the efficacy of 18F-FC119S as a positron emission tomography (PET) radiopharmaceutical for the imaging of Alzheimer’s disease (AD), we studied the drug absorption characteristics and distribution of 18F-FC119S in normal mice. In addition, we evaluated the specificity of 18F-FC119S for β-amyloid (Aβ) in the AD group of an APP/PS1 mouse model and compared it with that in the wild-type (WT) group. The behavior of 18F-FC119S in the normal mice was characteristic of rapid brain uptake and washout patterns. In most organs, including the brain, 18F-FC119S reached its maximum concentration within 1 min and was excreted via the intestine. Brain PET imaging of 18F-FC119S showed highly specific binding of the molecule to Aβ in the cortex and hippocampus. The brain uptake and binding values for the AD group were higher than those for the WT group. These results indicated that 18F-FC119S would be a candidate PET imaging agent for targeting Aβ plaque.

A silicon photomultiplier (SiPM) is considered a next generation photo-sensor for low-light applications. In this study, we propose and develop the general concept of a multipurpose submillimeter gamma-ray (MSG) imaging module that is applicable to most gamma-ray imaging devices. The main features of the MSG module are submillimeter intrinsic resolution, geometrically expandable structure, expandable data acquisition system, multi-energy capability and usability in intense magnetic fields. The elements of the gamma-ray detector are pixelated Ce:GAGG ( $31\times 31$ pixels, 0.8 mm pitch), a 1.5-mm acrylic light guide, and one SiPM array ( $8 \times 8$ pixels). The readout electronics are composed of a symmetric charge division resistive network, 16 channel preamplifiers, multiplexing amplifiers, and analog-to-digital converter (ADC) circuits. We use a subminiature field-programmable gate array (FPGA) board as a data acquisition system. To make the system more expandable, we apply a 10 GbE-based tree structure using a FPGA-based data acquisition board and switching hub. To verify multipurpose capabilities, the energy spectra and the flood images are obtained using Co-57, Na-22, and Cs-137 isotopes. We measure temperature characteristics of the detector module. A pinhole image is obtained to confirm high resolution property. The maximal data transfer rate that is measured using dummy gamma-ray event packets is 963.143 Mbps. This detector module can be applied to nuclear medicine imaging devices and radiation monitoring systems.

In this study, Zn1.10CuxMn1.90-xO4 (0 ≤ x ≤ 0.15) systems were prepared through the conventional solid state reaction method. All specimens were sintered in air at 1200 °C for 12 h and cooled at a rate of 2 °C/min to 800 °C, subsequently quenching to room temperature. Structural investigations were carried out using X-ray diffraction patterns and energy dispersive spectrometry. For x ≥ 0.10, formation of a tetragonal phase with a Zn-rich Zn-Cu-Mn-O segregated second phase was observed. In the microstructure, the grain size increased from 5.10 μm to 9.68 μm with an increase in Cu content. The resistivity at room temperature, B-value, responsivity and detectivity of the Zn1.10Cu0.05Mn1.85O4 specimen were found to be 300.2 kΩ·cm, 4665, 0.025 V/W, and 2.12 ×104 cmHz1/2/W, respectively.

The aim of this study is to design and evaluate a multi-pinhole (MP) collimator for a gamma imaging system that requires a high sensitivity, organ-specific, and small footprint. To ensure these requirements, we designed an eight-hole collimator that can be integrated into a small field-of-view gamma camera for imaging the thyroid or relatively sized organs. Each pinhole was designed to have a cylindrical shape with a 2-mm diameter. Experiments were performed with both a two-sphere phantom and a four-rod phantom. An image reconstruction based on the maximum likelihood expectation maximization with the distance-driven method was used for obtaining a 3-dimensional image. For improving the uniformity of the reconstruction image, we modeled the sensitivity of the cylindrical pinhole by calculating the area of the overlapped circle. The results show that the full width at half maximum values of the two-sphere phantom and the four-rod phantom were 7.56 mm (5-mm-diameter source) and 6.84 mm (5-mm-diameter rod), respectively. The scanning time can be reduced by up to 20 minutes in small-organ applications by using developed MP collimator. Thus, the results indicate that the proposed MP collimator is suitable for a fast scan time, as well as for organ-specific and small-footprint applications.

The aim of this study was to develop a high-throughput imaging method for single-photon emission computed tomography. We developed a target-oriented multi-pinhole collimator and limitedangle method for scanning small organs such as the thyroid. To maximize the resolution and the sensitivity of the collimator, we designed a two-level multi-pinhole collimator whose levels were optimized for concave body contours. One level had a center hole whereas the other had surrounding holes. The limited-angle scanning method was employed to obtain tomographic images by using the collimator located near the body contour of the target, and a corresponding image reconstruction algorithm was implemented. A small-field-of-view gamma camera was used to achieve a smaller footprint. The design of the collimator also considered the dimensions of used gamma camera. Evaluation studies were conducted using the Geant4 application for tomographic emission. The results showed the resolution of the proposed collimator to be more than twice that of the previously designed multi-pinhole collimator while maintaining the same efficiency. Given that the designed collimator can be changed by simply replacing the center hole, the suggested imaging method is suitable for studying not only the thyroid but also any organ whose diameter is less than 90 mm.

Vitexin (apigenin-8-C-d-glucopyranoside) is a flavonoid isolated from natural sources. It has been employed as an anti-oxidant, anti-inflammatory, and anti-cancer agent, and is used as a traditional Chinese medicine to treat a variety of illnesses. The present study investigated the effect of vitexin on osteoblast differentiation of C3H10T1/2 mesenchymal stem cells, MC3T3-E1 preosteoblast, mouse calvarial primary cells, and primary bone marrow stem cells (BMSCs). RT-PCR and quantitative PCR demonstrated that vitexin increased mRNA expression of the osteogenic genes distal-less homeobox 5 (Dlx5) and Runxt-related transcription factor 2 (Runx2). Vitexin also increased the Dlx5 and Runx2 protein levels, Smad1/5/9 phosphorylation, and alkaline phosphatase (ALP) activity. In addition, vitexin increased Runx2-luciferase activity. Moreover, knockdown of Runx2 attenuated the increase in ALP activity induced by vitexin. These results demonstrate that vitexin enhances osteoblast differentiation via Runx2.

The whole genome sequencing (WGS) has become a crucial tool in understanding genome structure and genetic variation. The MinION sequencing of Oxford Nanopore Technologies (ONT) is an excellent approach for performing WGS and it has advantages in comparison with other Next-Generation Sequencing (NGS): It is relatively inexpensive, portable, has simple library preparation, can be monitored in real-time, and has no theoretical limits on reading length. Sorghum bicolor (L.) Moench is diploid (2n = 2x = 20) with a genome size of about 730 Mb, and its genome sequence information is released in the Phytozome database. Therefore, sorghum can be used as a good reference. However, plant species have complex and large genomes when compared to animals or microorganisms. As a result, complete genome sequencing is difficult for plant species. MinION sequencing that produces long-reads can be an excellent tool for overcoming the weak assembly of short-reads generated from NGS by minimizing the generation of gaps or covering the repetitive sequence that appears on the plant genome. Here, we conducted the genome sequencing for S. bicolor cv. BTx623 while using the MinION platform and obtained 895,678 reads and 17.9 gigabytes (Gb) (ca. 25&times, coverage of reference) from long-read sequence data. A total of 6124 contigs (covering 45.9%) were generated from Canu, and a total of 2661 contigs (covering 50%) were generated from Minimap and Miniasm with a Racon through a de novo assembly using two different tools and mapped assembled contigs against the sorghum reference genome. Our results provide an optimal series of long-read sequencing analysis for plant species while using the MinION platform and a clue to determine the total sequencing scale for optimal coverage that is based on various genome sizes.

We evaluated the changes in treatment response over time after singleFifteen aggressive and 21 indolent lymphoma cases undergoing RIT were evaluated. All patients underwentThe treatment response to single RIT differed depending on NHL type. These findings suggest a need to establish an optimal treatment regimen based on NHL aggressiveness.

Background and purpose The aim of this study was to determine the diagnostic performance and safety of a new ¹⁸F-labeled amyloid tracer, ¹⁸F-FC119S. Methods This study prospectively recruited 105 participants, comprising 53 with Alzheimer's disease (AD) patients, 16 patients with dementia other than AD (non-AD), and 36 healthy controls (HCs). In the first screening visit, the Seoul Neuropsychological Screening Battery cognitive function test was given to the dementia group, while HC subjects completed the Korean version of the Mini Mental State Examination. Individuals underwent ¹⁸F-FC119S PET, ¹⁸F-fluorodeoxyglucose (FDG) PET, and brain MRI. The diagnostic performance of ¹⁸F-FC119S PET for AD was compared to a historical control (comprising previously reported and currently used amyloid-beta PET agents), ¹⁸F-FDG PET, and MRI. The standardized uptake value (SUV) ratio (ratio of the cerebral cortical SUV to the cerebellar SUV) was measured for each PET data set to provide semiquantitative analysis. All adverse effects during the clinical trial periods were monitored. Results Visual assessments of the ¹⁸F-FC119S PET data revealed a sensitivity of 92% and a specificity of 84% in detecting AD. ¹⁸F-FC119S PET demonstrated equivalent or better diagnostic performance for AD detection than the historical control, ¹⁸F-FDG PET (sensitivity of 80.0% and specificity of 76.0%), and MRI (sensitivity of 98.0% and specificity of 50.0%). The SUV ratios differed significantly between AD patients and the other groups, at 1.44±0.17 (mean±SD) for AD, 1.24±0.09 for non-AD, and 1.21±0.08 for HC. No clinically significant adverse effects occurred during the trial periods. Conclusions ¹⁸F-FC119S PET provides high sensitivity and specificity in detecting AD and therefore may be considered a useful diagnostic tool for AD.

Among the metal–oxide nanoparticles, pure and doped zinc oxide (ZnO) has been widely studied due to their potential applications, such as electrical, thermal and optical materials. In this context, samples of undoped ZnO and Cr-doped ZnO powders were prepared using a solution-combustion route. The formation of the combustion products was confirmed by X-ray diffraction analysis. The samples were well characterized using the Fourier transform infrared spectroscopy and scanning electron microscopy techniques. In the sample, photoluminescence studies showed that ZnO could be excited at 267 nm, while an ultraviolet emission centred at $${\sim }383\,\hbox {nm}$$ was exhibited. Antibacterial-activity testing was carried out using the disc-diffusion method.

In July 2017, a medical accident occurred in South Korea, in which I-iodide solution was misadministered to the wrong patient. Although the International Commission on Radiological Protection provided internal dose coefficients for iodine for blocked thyroid, they were not reliable enough for determining the dose to the patient (whose thyroid uptake was incompletely blocked) due to a discrepancy in biokinetics. Therefore, a personalized dose assessment was performed to derive the individual-specific dose coefficients for the patient. Initially, the thyroid biokinetics of the patient were statistically clarified by fitting bioassay monitoring results and the corresponding predicted bioassay values, which were calculated repeatedly for varying iodine transfer rates in an iodine biokinetic model. After determining the transfer rate for the patient, the individual-specific dose coefficients were then calculated in accordance with latest recommendations of the International Commission on Radiological Protection. According to the individual-specific biokinetics, the 24 h thyroid uptake fraction of iodine was estimated as 0.52%. The thyroid absorbed dose of the patient was evaluated as 21.2 Gy, which differed greatly (by about 9 Gy) from the dose evaluated simply using the reference data for blocked thyroid uptake. The personalized dose assessment carried out for the patient not only reduced considerable uncertainties in the internal dose calculation, but also improved the reliability of the calculated internal dose by adopting the latest dosimetric data, including specific absorbed fraction values based on voxel phantoms. Through the dose assessment of the patient, the methodology of personalized dose assessment considering individual-specific biokinetics was developed.

Single-photon emission computed tomography (SPECT) is a nuclear medical imaging method enabling the user to view functional images of patients. The collimator, which is an essential component of the SPECT, limits the direction of the incident gamma rays, such that the distribution of the gamma photons from the body can be observed. Collimators are composed of shielding materials with high atomic number and density, thus it is difficult to fabricate them in complex shapes. Among the existing collimators, the pinhole collimator consists of a small aperture perforated in a shielding material, and the modification of the pinhole parameters, such as the hole diameter and acceptance angle, during the scan is also challenging. A variable pinhole (VP) collimator comprises several thin tungsten layers with various hole sizes. Thus, the pinhole parameters can be varied for the region of interest (ROI) by forming the desired pinhole shape using a combination of holes. In this study, we implemented the concept of a VP collimator and applied it in a SPECT system to enhance its performance. The collimator was composed of five layers of with a diameter of 170 mm and thickness of 1 mm and with six holes of different sizes in each layer. Two point sources (Co-57, 122 keV) were used for the performance analysis by changing the system parameters. The spatial resolution and sensitivity of the SPECT system were affected by the variation of the pinhole diameters, with the peak-to-valley ratio increasing by up to 3.3 times with the increase in the magnification of the SPECT system. Two line source phantoms (Tc-99m, 140 keV) with an internal diameter of 1 mm were used for the performance evaluation of the system. The phantoms were positioned 20 mm apart inside the ROI with a diameter of 50 mm at a position of 29 mm from the object center. By applying the VP collimator, the resolution and the sensitivity performance were improved, achieving a full width at half maximum value of 2.7 times and counts of 2.8 times those of the conventional SPECT system. In future research, we aim to improve the system efficiency by conducting simultaneous experimental driving test of the dual-head VP collimator SPECT system.

Aims Mammalian circadian rhythms regulate many metabolic processes. Recent studies suggest that brain and muscle Arnt-like 1 (BMAL1), an important component of mammalian circadian rhythm, is associated with insulin signaling. Several studies have shown that insulin is associated with bone metabolism; however, the relationship between BMAL1 and osteoblasts remains unclear. Main methods Expression of osteogenic markers and Bmal1 in MC3T3-E1 cells was measured by RT-PCR and Western blotting. Alizarin red S staining was performed to assess matrix mineralization in MC3T3-E1 cells. Key findings mRNA levels of osteogenic genes and Bmal1 were up-regulated in MC3T3-E1 cells upon insulin treatment. In addition, Bmal1 overexpression increased the expression of osteogenic genes including inhibitor of DNA binding (Id1), Runt-related transcription factor 2 (Runx2), and osteocalcin (OC). Interestingly, expression of Bone morphogenetic protein-2 (BMP2), an important upstream factor of Id1, Runx2, and OC, was markedly increased by Bmal1. Finally, we confirmed that insulin-induced BMP2 expression was attenuated in Bmal1 knockout (KO) cells. PCR analysis and alizarin red S staining showed that insulin-mediated increases gene expression and calcium deposition were reduced in Bmal1 KO cells compared to wild-type cells. Significance Taken together, these results demonstrate that Bmal1 promotes osteoblast differentiation by regulating BMP2 expression in MC3T3-E1 cells.

The aim of this study was to assess the clinical activity and toxicity of 131I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone). Patients who had been diagnosed with advanced stage (Ann Arbor III or IV) or bulky stage II DLBCL and achieved complete or partial response after six to eight cycles of R-CHOP were enrolled. A total of 16 patients were enrolled and treated with a single dose of 131I-rituximab as consolidation therapy after the completion of six or eight cycles of R-CHOP between December 2005 and June 2011. This trial was terminated before the scheduled enrollment owing to low recruitment. Among the 16 patients who were treated with consolidative 131I-rituximab, 6 achieved complete response (CR) after three cycles of R-CHOP, and another 9 patients further achieved CR after the completion of six or eight cycles of R-CHOP. During the median follow-up period of 73 months, only four patients (25 %) experienced relapse. Two-year relapse-free survival was 88 %, and 5-year relapse-free survival was 81 %. Grade 3 or 4 treatment-related toxicity occurred in four patients and included neutropenia and thrombocytopenia. 131I-rituximab showed promising efficacy as consolidation treatment for patients with DLBCL. A future randomized phase III study to confirm our results is warranted.

To obtain an additional pharmacological agent for the diagnosis of inflammation, we investigated the medical use of (89)Zr-oxalate as a positron emission tomography (PET) probe for the in vivo imaging of inflammation and compared its efficacy to that of 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) and sodium [(18)F]fluoride. (89)Zr-oxalate exhibited observable higher uptake in a macrophage cell line than in tumor cells. The inflammatory lesions and tumors were clearly visualized by PET imaging and autoradiography using (89)Zr-oxalate. Compared to [(18)F]FDG and sodium [(18)F]fluoride, (89)Zr-oxalate demonstrated a high selectivity index to the tumor at an early time point after injection and to inflammation at a delayed time point after injection (24 h). Through histological examination, large numbers of macrophages and neutrophils were observed in the tumor lesions with the highest (89)Zr-oxalate uptake. In a rheumatoid arthritis (RA) mouse model, (89)Zr-oxalate demonstrated a high level of accumulation in inflammatory lesions. (89)Zr-oxalate is a new strategic tool for tumor imaging and inflammatory processes.

In this study, Ni(MnCu)O (x=0~0.25) specimens were prepared by using a conventional mixed oxide method. All specimens were sintered in air at 1,200℃ for 12 h and cooled at a rate of 2℃/min to 800℃, subsequently quenching to room temperature. We investigated the structural and electrical properties of Ni  (Mn  Cu  )O  specimens with variation of CuO amount for the application of NTC thermistors. As results of X-ray diffraction patterns, all specimens showed the formation of a complete solid solution with cubic spinel phase. The relationship between ln ρ and the reciprocal of absolute temperature(1/T) for the NTC thermistors was shown linearity, which exhibited the typical NTC thermistor properties. With increasing the amount of CuO, resistivity at room temperature, B-value, and temperature coefficient resistance decreased.

Positron emission tomography (PET) can be utilized in particle beam therapy to verify the dose distribution of the target volume as well as the accuracy of the treatment. We present an in-beam PET scanner that can be integrated into a particle beam therapy system. The proposed PET scanner consisted of 14 detector modules arranged in a C-shape to avoid blockage of the particle beam line by the detector modules. Each detector module was composed of a 9×9 array of 4.0 mm×4.0 mm×20.0 mm LYSO crystals optically coupled to four 29-mm-diameter PMTs using the photomultiplier-quadrant-sharing (PQS) technique. In this study, a Geant4 Application for Tomographic Emission (GATE) simulation study was conducted to design a C-shaped PET scanner and then experimental evaluation of the proposed design was performed. The spatial resolution and sensitivity were measured according to NEMA NU2-2007 standards and were 6.1 mm and 5.61 cps/kBq, respectively, which is in good agreement with our simulation, with an error rate of 12.0%. Taken together, our results demonstrate the feasibility of the proposed C-shaped in-beam PET system, which we expect will be useful for measuring dose distribution in particle therapy.

[18F]Mefway is a positron emission tomography (PET) radioligand for quantification of the brain serotonin 1A (5-HT1A) receptor density. The purpose of this study was to evaluate the radiation safety of [18F]Mefway in humans. Six healthy volunteers (three males and three females) were whole-body PET scanned for 114 min after injection of [18F]Mefway (226 ± 35 MBq). Estimated radiation doses were determined by the OLINDA/EXM software. [18F]Mefway was safe and well tolerated by all subjects. Residence time ranges from 0 (gallbladder) to 0.822 h (urinary bladder wall). While the estimated radiation doses in the reproductive and blood-forming organs were below 13.35–22.87 μSv/MBq, radiation dose in the urinary bladder wall was 471 μSv/MBq. The mean effective dose was 40.23 ± 6.63 μSv/MBq. For a typical single injection of 185 MBq (5 mCi), the dose will result in 87.1 mSv for the urinary bladder wall. To reduce radiation burden, the bladder voiding can be used before [18F]Mefway PET scan.

A computational and experimental study has been carried out to produce highly value-added {100} textured steel sheets. This study is based on an idea that an anisotropic surface segregation tendency of impurity atoms would cause an inversion of relative surface energy between {110} and {100} surfaces in bcc Fe and may induce the formation of {100} texture in steel sheets during grain coarsening. A phase field model that can consider surface segregation of impurity atoms (and resultant decrease of surface energy) and grain growth simultaneously is newly developed. The phase field model and surface property data obtained from an atomistic approach are used to simulate grain coarsening behavior of phosphorus-containing iron and to find an optimum process condition that can induce the {100} texture in steel sheets. The phase field simulation indicates that the surface segregation and resultant change in the relative difference in surface energy should be accomplished before the start of grain coarsening for an effective formation of the {100} texture. A strong {100} texture is indeed generated experimentally in phosphorus-containing bcc Fe-3.5wt% Si steel sheets through a two-step annealing process, one at a relatively low temperature where only surface segregation can occur but not the grain coarsening and the other at a relatively high temperature where the grain coarsening can also occur.

The aim of the present study is to establish a time and cost effective Na[18F]F preparation method. The process is composed of absorbing radioactive impurities with cation exchange cartridge (CM), trapping 18F-fluroide with QMA cartridges, and formulating the product. The total preparation time determined at the end of bombardment was 4 min and the radiochemical yield was 82 % (n = 29). The final formulated Na[18F]F solution satisfies the USP criteria for quality control.

For NiMn2O4 systems, the mixed valence of manganese on B-sites arises from the displacement of bivalent cations, such as Ni2+, from A-sites to B-sites which results in a corresponding proportion of Mn3+ cations on B-sites disproportionate to Mn2+ and Mn4+, and the Mn2+ cations move to the A-sites to compensate Ni2+ vacancies. With the assistance of random crystal field fluctuations and the mixed valence of manganese eventually leads to the formation of localized small polarons which accomplish a thermally activated hopping conduction between Mn3+ and Mn4+ cations on octahedral sites. In this study, we have investigated the structural and electrical properties of NixMn3-xO4 system. And, we have comprehensively measured the electrical transport mechanism, the temperature coefficient of resistance and infrared detection performance for the application of infrared radiation detectors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Carbohydrate responsive element binding protein (ChREBP) is a major transcription factor of lipogenesis regulated by glucose status in the liver. However, the function of ChREBP in osteogenic differentiation is unclear. The present study examined the role of ChREBP in osteoblast differentiation in MC3T3-E1 preosteoblast cell line. The mRNA expression of ChREBP, protein phosphatase 2A catalytic subunit-α (PP2A Cα) and the osteogenic genes such as, DNA-binding protein inhibitor (Id1), runt-related transcription factor-2 (Runx2), and alkaline phosphatase (ALP) was measured by qPCR and RT-PCR. Runx2, ChREBP, and PP2A Cα, protein levels were evaluated by Western blotting. ALP staining experiment was carried out to evaluate ALP enzyme activity, and a luciferase reporter assay was performed to analyze Runx2 transcriptional activity. Expression of ChREBP and PP2A Cα did not change during bone morphogenetic protein-2 (BMP2)-induced osteoblast differentiation. Overexpression of ChREBP reduced the osteogenic genes (Runx2 and ALP) expression and ALP activity, while knockdown of ChREBP had the opposite effects. Overexpression of PP2A Cα increased ChREBP expression, while inhibition of PP2A Cα using okadaic acid not only inhibited the expression of ChREBP, but also restored the mRNA and protein expression of Runx2 and activity of ALP enzyme. These results demonstrate that ChREBP inhibits BMP2-induced osteoblast differentiation in a PP2A Cα- dependent manner.

Characteristic x rays generated by a collision between a tungsten target and relativistic electron beams generated from a compact electrostatic accelerator based on a Marx generator and a Blumlein pulse-forming line can induce transient ionizing radiation in electronics. While the decelerated electron beam is close to a collector out of range of an external magnetic field, Bremsstrahlung x rays occur at the same time. Compton scattering also occurs through secondary reaction interactions with quasi-stationary particles such as ejected inner shell electrons or photons. During a simulation, a semiconductor process is used to analyze the effects and processes of photocurrents derived from the flow of the drain current when transient pulses generated from the compact electrostatic accelerator are incident in the pMOSFET-AD420-based detector. The photocurrent induced from the detector is also measured by experimental results in comparison with a computer simulation, and a photocurrent detection experiment was then conducted with a high-pulse-current compact electrostatic accelerator. In addition, data pertaining to the irradiation dose rate and photon emission rate were obtained. In order to confirm the radiation pattern in the situation of Compton scattering, the ionizing radiation effect in the photosensitive phosphor was identified using a fluorescent lamp. During the experiment, a relativistic electron beam operating at high energy and current levels at a maximum of 1MeV-10 kA was utilized.

In the recent past, gamma-ray imaging detectors have achieved an intrinsic spatial resolution of less than 1 mm within a few centimeters of a useful field of view (UFOV). Unlike to conventional gamma cameras, which are large and heavy, the compact gamma-ray imaging detectors can improve the performances of the gamma cameras used in the various fields. In this study, we developed a sub-miniature gamma camera for a multimodal imaging system. The camera has a gamma-ray detector, miniature electronics modules, and a diverging hole collimator . The detector consisted of the sub-millimeter pixelated Ce:GAGG array and the silicon photomultiplier (SiPM) array module. We organized the miniature electronics modules according to the functions; an MPPC base board, analog signal processing board, integrated power supply board, and compact data acquisition (DAQ) base board. The diverging hole collimator widened an imaging area of the gamma camera from the UFOV of the detector. On the detector side, dimensions of each hole and septa were identical to the pixel and inter-pixel thickness of the reflector of scintillator array. For the intrinsic performance test, we acquired a flood map image of 729 (27 × 27) scintillator pixels, and the energy resolution was 18.9% for an integrated energy histogram of 99m Tc (140 keV). For the extrinsic performance test, we used the 57Co sheet source, and made a 99m Tc line source using a capillary tube. The sources located at 10 cm apart from the collimator surface. The imaging area was three times wider than the UFOV of the detector. The system sensitivity was 19 CPM/ μ Ci and the spatial resolution was 3.5 mm. The usability of the proposed gamma camera will not be confined to existing applications due to its compactness and novelty.

Boron Neutron Capture Therapy (BNCT) is an approach of cancer treatment using high reactivity of boron with neutron. In BNCT, image-based monitoring of the reactivity in target region is important for the safety of patient and the evaluation of efficacy in treatment. In this study, we designed and evaluated a system of GAGG based prompt gamma ray imaging (PGI) camera with parallel hole collimator using Monte Carlo (MC) simulation. GATE (v7.0) packages have been used in the MC simulation. Various parameters for parallel hole collimator design were considered. In the MC simulation, a spherical water phantom was placed at the center of field of view (FOV) of gamma camera and a spherical boron phantom was positioned at the center of the water phantom. The diameter of water phantom was changed to evaluate the effect of scatter and annihilation photons in PGI. As the neutron energy increased, the range of the neutron in the water increased. As the amount of scattering material increased, image quality was decreased due to the increased amount of scatter and annihilation gamma ray of 511 keV components. The septal penetration ratio of 3.5 %, which is generally considered suitable to nuclear medicine imaging, was not acceptable in PGI for differentiating target. For PGI in BNCT, higher value of septal penetration fraction should be considered in collimator design. Optimized design of collimator and scatter correction would be necessary for the better quality of PGI of BNCT.

Gadolinium-neutron capture therapy (Gd-NCT) is based on the nuclear capture reaction that occurs when 157Gd is irradiated with low energy thermal neutrons to primarily produce gamma photons. Herein, we investigated the effect of neutron capture therapy (NCT) using a small molecular gadolinium complex, Gd-DO3A-benzothiazole (Gd-DO3A-BTA), which could be a good candidate for use as an NCT drug due to its ability to enter the intracellular nuclei of tumor cells. Furthermore, MRI images of Gd-DO3A-BTA showed a clear signal enhancement in the tumor, and the images also played a key role in planning NCT by providing accurate information on the in vivo uptake time and duration of Gd-DO3A-BTA. We injected Gd-DO3A-BTA into MDA-MB-231 breast tumor-bearing mice and irradiated the tumors with cyclotron neutrons at the maximum accumulation time (postinjection 6 h); then, we observed the size of the growing tumor for 60 days. Gd-DO3A-BTA showed good therapeutic effects of chemo-Gd-NCT for the in vivo tumor models. Simultaneously, the Gd-DO3A-BTA groups ([Gd-DO3A-BTA(+), NCT(+)]) showed a significant reduction in tumor size (p<0.05), and the inhibitory effect on tumor growth was exhibited in the following order: [Gd-DO3A-BTA(+), NCT(+)] > [Gd-DO3A-BTA(+), NCT(−)] > [Gd-DO3A-BTA(−), NCT(+)] > [Gd-DO3A-BTA(−), NCT(−)]. On day 60, the [Gd-DO3A-BTA(+), NCT(+)] and [Gd-DO3A-BTA(−), NCT(−)] groups exhibited an approximately 4.5-fold difference in tumor size. Immunohistochemistry studies demonstrated that new combinational therapy with chemo-Gd-NCT could treat breast cancer by both the inhibition of tumor cell proliferation and induction of apoptosis-related proteins, with in vivo tumor monitoring by MRI.

An optical/nuclear hybrid surgical technique using ICG-99mTc-nanocolloid can improve lesion detectability by detecting both fluorescence and gamma signals. However, a hybrid multimodal laparoscope that can obtain both NIR and gamma images is not available yet. In this work, we present a proof-of-concept study of a prototype multimodal laparoscope that can provide simultaneous NIR/gamma/visible imaging using wavelength division multiplexing. The performances of optical and gamma imaging were evaluated using a USAF 1951 negative resolution target and 99mTc-filled tumor-like sources, respectively. Simultaneous NIR/gamma/visible images of two Eppendorf tubes containing a mixture of 99mTc-ICG are presented.

The RNA-binding motif protein 3 (RBM3) belongs to a small group of proteins whose synthesis increases during hypothermia while global protein production is slowed down. Bone homeostasis is maintained by a balance between bone resorption and bone formation. Osteoblasts are key components of the bone and have an important role in bone remodeling cycle. However, hypothermia-induced RBM3 between osteoblasts remains unclear. At 32°C, expression of RBM3 and Runx2 was increased in a time-dependent manner and mineralization was also increased. RBM3 was also increased in a time-dependent manner under osteogenic conditions. Overexpression of RBM3 increased the expression of osteogenic genes such as Runx2 and OC. The osteogenic condition-induced expressions of RBM3, Runx2 and OC gene were decreased by RBM3 siRNA. Moreover, RBM3 promoted ERK and p38 phosphorylation. The inhibitor of ERK decreased the expression of Runx2 but did not affect the expression of RBM3. Taken together, these results demonstrate that RBM3 stimulates osteoblast differentiation via the ERK signaling pathway.

Kisspeptin-10 (KP-10) acts as a tumor metastasis suppressor via its receptor, G-protein-coupled receptor 54 (GPR54). The KP-10-GPR54 system plays an important role in embryonic kidney development. However, its function in osteoblast differentiation is unknown. Osteoblast differentiation is controlled by a range of hormones and cytokines, such as bone morphogenetic protein (BMPs), and multiple transcription factors, such as Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and Distal-less homeobox 5 (Dlx5). In the present study, KP-10-treatment significantly increased the expression of osteogenic genes, including mRNA and protein levels of BMP2, in C3H10T1/2 cells. Moreover, KP-10 induced BMP2-luc activity and increased phosphorylation of Smad1/5/9. In addition, NFATc4 specifically mediated KP-10-induced BMP2 gene expression. However, KP-10 treatment did not induce expression of the BMP2 and Runx2 genes in GPR54−/− cells. To examine whether KP-10 induced secretion of BMP2 to the culture medium, we used the conditioned-medium (C.M) of KP-10 treated medium on C3H10T1/2 cells. Dlx5 and Runx2 expressions were higher in GPR54−/− cells treated with C.M than in those treated with KP-10. These results demonstrate that BMP2 protein has an autocrine effect upon KP-10 treatment. Taken together, these findings suggest that KP-10/GPR54 signaling induces osteoblast differentiation via NFATc4-mediated BMP2 expression.

Purpose. 18F-FC119S is a positron emission tomography (PET) tracer for imaging β-amyloid (Aβ) plaques in Alzheimer’s disease (AD). The aim of this study is to evaluate the efficacy of 18F-FC119S in quantitating Aβ deposition in a mouse model of early amyloid deposition (5xFAD) by PET. Method. Dynamic 18F-FC119S PET images were obtained in 5xFAD (n=5) and wild-type (WT) mice (n=7). The brain PET images were spatially normalized to the M. Mirrione T2-weighted mouse brain MR template, and the volumes of interest were then automatically drawn on the cortex, hippocampus, thalamus, and cerebellum. The specific binding of 18F-FC119S to Aβ was quantified as the distribution volume ratio using Logan graphical analysis with the cerebellum as a reference tissue. The Aβ levels in the brain were also confirmed by immunohistochemical analysis. Result. For the 5xFAD group, radioactivity levels in the cortex, the hippocampus, and the thalamus were higher than those for the WT group. In these regions, specific binding was approximately 1.2-fold higher in 5xFAD mice than in WT. Immunohistochemistry supported these findings; the 5xFAD showed severe Aβ deposition in the cortex and hippocampus in contrast to the WT group. Conclusion. These results demonstrated that 18F-FC119S PET can successfully distinguish Aβ depositions in 5xFAD mice from WT.