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Vertically aligned graphite substrate (VGS)-copper packaging was renowned for improving the robustness against the thermal gradient loading by using micro texturing. The micro-groove array with a line width of 50 μm and a pitch of 100 μm was formed into the VGS by controlling the line depth with the use of fast-rate oxygen plasma etching. Three micro-grooved VGS specimens were wet-plated to fill these microgrooves with copper deposits and to cover the VGS surfaces. The nearly full-deposited VGS-Copper specimens were subjected to a severe thermal transient loading test. The simply Cu-covered package and shallow rib-structured VGS-Cu packages were damaged to delaminate at their interfaces. The VGS-Cu package with the copper rib structure with a height of 50 μm experienced no delamination. This rib-structured VGS-copper package with high rib height had sufficient robustness against the severe thermal transients even with the proof of homogeneous thermal spreading capacity.

Mouse double minute 2 (MDM2) is an oncoprotein that is frequently overexpressed in tumors and enhances cellular transformation. Owing to the important role of MDM2 in modulating p53 function, it is crucial to understand the mechanism underlying the regulation of MDM2 levels. We identified ribosomal protein S4X-linked (RPS4X) as a novel binding partner of MDM2 and showed that RPS4X promotes MDM2 stability. RPS4X suppressed polyubiquitination of MDM2 by suppressing homodimer formation and preventing auto-ubiquitination. Moreover, RPS4X inhibited the interaction between MDM2 and Cullin1, a scaffold protein of the Skp1-Cullin1-F-box protein (SCF) complex and an E3 ubiquitin ligase for MDM2. RPS4X expression in cells enhanced the steady-state level of MDM2 protein. RPS4X was associated not only with MDM2 but also with Cullin1 and then blocked the MDM2/Cullin1 interaction. This is the first report of an interaction between ribosomal proteins (RPs) and Cullin1. Our results contribute to the elucidation of the MDM2 stabilization mechanism in cancer cells, expanding our understanding of the new functions of RPs.

The safety and effectiveness of chemotherapy in elderly patients with biliary tract cancer (BTC) remain unclear. Therefore, we retrospectively reviewed patients who underwent chemotherapy for locally advanced, metastatic, or recurrent BTC at our institution from January 2016 to December 2021. Of the 283 included patients, 91 (32.5%) were aged 75 years or older when initiating chemotherapy. Elderly patients were more likely than non-elderly patients to receive monotherapy with gemcitabine or S-1 (58.7% vs. 9.4%, p < 0.001) and were less likely to experience grade 3–4 toxicities (55.4% vs. 70.2%, p = 0.015). The rates of termination due to intolerance (6.5% vs. 5.8%, p = 0.800) and transition to second-line chemotherapy (39.1% vs. 40.3%, p = 0.849) were similar between groups. In the overall cohort, age was not an independent predictor of overall survival (OS). Within the elderly cohort, there were no differences in severe adverse events between patients receiving monotherapy and combination therapy (50.0% vs. 63.2%, p = 0.211). Median OS was longer in the combination therapy group (10.4 vs. 14.1 months; p = 0.010); however, choice of monotherapy was not an independent predictor of overall survival. Monotherapy appears to be a viable alternative in selected elderly BTC patients.

In this study, we evaluated the effect of several promoters on the transfection activity and immune-induction efficiency of a plasmid DNA (pDNA)/polyethylenimine/γ-polyglutamic acid complex (pDNA ternary complex). Model pDNAs encoding firefly luciferase (Luc) were constructed with several promoters, such as simian virus 40 (SV40), eukaryotic elongation factor 1 alpha (EF1), cytomegalovirus (CMV), and chicken beta actin hybrid (CBh) (pSV40-Luc, pEF1-Luc, pCMV-Luc, and pCBh-Luc, respectively). Four types of pDNA ternary complexes, each with approximately 145-nm particle size and −30-mV ζ-potential, were stably constructed. The pDNA ternary complex containing pSV40-Luc showed low gene expression, but the other complexes containing pEF1-Luc, pCMV-Luc, and pCBh-Luc showed high gene expression in DC2.4 cells and spleen after intravenous administration. After immunization using various pDNA encoding ovalbumin (OVA) such as pEF1-OVA, pCMV-OVA, and pCBh-OVA, only the pDNA ternary complex containing pCBh-OVA showed significant anti-OVA immunoglobulin G (IgG) induction. In conclusion, our results showed that the CBh promoter is potentially suitable for use in pDNA ternary complex-based DNA vaccination.

Quick decision making is a vital factor for a successful pass in soccer games. Many previous studies of decision making in soccer focused on motor execution, but inhibitory processing has remained unclear. This study aimed to clarify the differences in motor execution and inhibitory among Japanese collegiate soccer players with different skill levels. We evaluated the behavioral data and event-related potentials in the high-skilled, low-skilled, and novice groups during the Go/No-go and pass choice reaction tasks. The reaction time (RT) was significantly shorter in the high group than in the novice group, and RT variability was small in the high group. The amplitude of the N2 component was significantly larger in the high group than in the low and novice groups, and the latency of the P3 component was significantly shorter in the high and low groups than in the novice group during the pass choice reaction task. The subtracted No-go N2 amplitude was also significantly larger in the high and low groups than in the novice group, and correlations existed between the RT, RT variability, and the subtracted No-go N2 amplitude during these tasks. These data indicate that soccer players’ behavioral responses and inhibition processing decision-making activities are associated with skill levels.

An acicular microtextured sheet was developed as a heat radiation device from the high-temperature source to the cooling medium in the infrared (IR) spectrum. The copper surface was modified by acicular micro-texturing to place a semi-regular micro-/nano-cone structure onto it. FT-IR (Fourier transformation IR) spectroscopy was utilized to measure the transmittance diagram in near-IR to far-IR wavelengths. The wavelength (λ) of 6.7 μm, where the highest absorbance valley was detected in the diagram, was equivalent to the doubled size of the micro-cone average height, with Have = 3.3 μm; λ ~ 2 × Have. The electromagnetic waves in the far-IR wavelength were emitted by acicular micro-textured metallic sheets. The heat radiation transfer experiment was performed to describe this low-temperature heat radiation behavior. No temperature rise was detected on the black-colored polycarbonate (BC-PC) plate away from the bare copper sheet without textures, located on the high-temperature source. The temperature increased by 4 K on the BC-PC plate using the acicular textured copper sheet device. The emitter temperature also decreased significantly by 50 K or 50% of the heat source temperature.

Catheterization of the right adrenal vein (rt.AdV) to obtain blood samples can often be difficult. The aim of the present study was to investigate whether blood sampling from the inferior vena cava (IVC) at its juncture with the rt.AdV can be an ancillary to sampling of blood directly from the rt.AdV. This study included 44 patients diagnosed with primary aldosteronism (PA) in whom AVS with adrenocorticotropic hormone (ACTH) was performed, resulting in a diagnosis of idiopathic hyperaldosteronism (IHA) (n = 24), and patients diagnosed with unilateral aldosterone-producing adenoma (APA) (n = 20; rt.APA = 8, lt.APA = 12). In addition to regular blood sampling, blood was also sampled from the IVC, as the substitute rt.AdV [S-rt.AdV]. Diagnostic performance with the conventional lateralized index (LI) and the modified LI using the S-rt.AdV were compared to examine the utility of the modified LI. The modified LI of the rt.APA (0.4 ± 0.4) was significantly lower than those of the IHA (1.4 ± 0.7) (p < 0.001) and the lt.APA (3.5 ± 2.0) (p < 0.001). The modified LI of the lt.APA was significantly higher than those of the IHA (p < 0.001) and rt.APA (p < 0.001). Likelihood ratios to diagnose rt.APA and lt.APA using the modified LI with threshold values of 0.3 and 3.1 were 27.0, and 18.6, respectively. The modified LI has the potential to be an ancillary method for rt.AdV sampling in cases in which rt.AdV sampling is difficult. Obtaining the modified LI is extremely simple, which might complement conventional AVS.

Japanese Black cattle (Japanese Wagyu) beef is attracting attention for its aroma and marbling, and its handling is increasing worldwide. Here, we focused on the origin discrimination of Wagyu beef and analyzed the nutritional components of Japanese Wagyu (produced in multiple prefectures of Japan), Hybrid Wagyu (a cross between Angus and Wagyu cattle born in Australia and transported to Japan), and Australian Wagyu beef using mass spectrometry (MS). Triple-quadrupole liquid chromatography–MS was used to clarify the molecular species of lipids in Wagyu beef. Fourteen classes of lipids were separated, and 128 different triacylglycerides (TGs) were detected. A simple comparative analysis of these TGs using high-performance liquid chromatography revealed significantly higher levels of triolein (C18:1/C18:1/C18:1; abbreviated OOO) and C18:1/C18:1/C16:1 (OOPo) in Japanese Wagyu. Wagyu elements beef were comprehensively analyzed using inductively coupled plasma (ICP)–MS and ICP–optical emission spectrometry. We found significant differences in the rubidium, cesium, and lithium levels of Japanese and Australian Wagyu beef. On comparing metabolites using gas chromatography–MS, we identified significant differences in the levels of amino acids and other components of the Japanese and Australian Wagyu beef. These results suggest the possibility of determining the origin of Wagyu cattle breeds using MS and genetic discrimination.

Aroma is an essential factor for meat quality. The meat of Japanese Black cattle exhibits fine marbling and a rich and sweet aroma with a characteristic lactone composition. The mechanism of lactone formation associated with beef aroma has not been elucidated. In this study, we examined the precursors of γ-hexalactone, an indicator of the sweet aroma of beef and identified the mechanism underlying γ-hexalactone production. A low-temperature vacuum system was used to prepare beef tallow from Japanese Black cattle and Holstein cattle. The odor components were identified using headspace–gas chromatography. The analysis revealed that γ-hexalactone, γ-dodecalactone, δ-tetradecalactone, and δ-hexadecalactone were present as sweet aroma components of beef tallow prepared from marbling and muscle. Since we previously reported that γ-hexalactone formation correlates with linoleic acid content in beef, we analyzed ten oxidized fatty acids derived from linoleic acid by liquid chromatography–triple quadrupole mass spectrometry and detected two hydroxy-octadecadienoic acids (9S-HODE and 13S-HODE) in beef tallow. Significant differences in arachidonic acid 15-lipoxygenase and cyclooxygenase protein expression levels among subcutaneous fat, intramuscular fat, and muscle tissue were observed. Our results suggest that the combination of linoleic acid and the expression of lipid oxidase derived from beef muscle and intramuscular fat produce hydroxy fatty acids that result in a sweet aroma.

Currently used techniques for intraoperative assessment of tumor resection margins are time-consuming and laborious and, more importantly, lack specificity. Moreover, pathological diagnosis during surgery does not often give a clear outcome. Recent advances in mass spectrometry (MS) and instrumentation have made it possible to obtain detailed molecular information from tissue specimens in real-time, with minimal sample pre-treatment. Probe Electro Spray Ionization MS (PESI-MS), combined with artificial intelligence (AI), has demonstrated its effectiveness in distinguishing liver cancer tissues from healthy tissues in a large Italian population group. As the MS profile can reflect the patient’s ethnicity, dietary habits, or particular operating room procedures, the AI algorithm must be well trained to distinguish different groups. We used a large dataset composed of liver tumor and healthy specimens, from the Italian and Japanese populations, to develop a versatile algorithm free from ethnic bias. The system can classify tissues with discrepancies

In mass spectrometry-based metabolomics, the differences in the analytical results from different laboratories/machines are an issue to be considered because various types of machines are used in each laboratory. Moreover, the analytical methods are unique to each laboratory. It is important to understand the reality of inter-laboratory differences in metabolomics. Therefore, we have evaluated whether the differences in analytical methods, with the exception sample pretreatment and including metabolite extraction, are involved in the inter-laboratory differences or not. In this study, nine facilities are evaluated for inter-laboratory comparisons of metabolomic analysis. Identical dried samples prepared from human and mouse plasma are distributed to each laboratory, and the metabolites are measured without the pretreatment that is unique to each laboratory. In these measurements, hydrophilic and hydrophobic metabolites are analyzed using 11 and 7 analytical methods, respectively. The metabolomic data acquired at each laboratory are integrated, and the differences in the metabolomic data from the laboratories are evaluated. No substantial difference in the relative quantitative data (human/mouse) for a little less than 50% of the detected metabolites is observed, and the hydrophilic metabolites have fewer differences between the laboratories compared with hydrophobic metabolites. From evaluating selected quantitatively guaranteed metabolites, the proportion of metabolites without the inter-laboratory differences is observed to be slightly high. It is difficult to resolve the inter-laboratory differences in metabolomics because all laboratories cannot prepare the same analytical environments. However, the results from this study indicate that the inter-laboratory differences in metabolomic data are due to measurement and data analysis rather than sample preparation, which will facilitate the understanding of the problems in metabolomics studies involving multiple laboratories.

Comprehensive safety evaluation methodologies for automated driving systems that account for the large complexity real traffic are currently being developed. This work adopts a scenario-based safety evaluation approach and aims at investigating an advanced methodology to generate test cases by applying heuristics to naturalistic driving data. The targeted requirements of the generated test cases are severity, exposure, and realism. The methodology starts with the extraction of scenarios from the data and their split in two subsets—containing the relatively more critical scenarios and, respectively, the normal driving scenarios. Each subset is analysed separately, in regard to the parameter value distributions and occurrence of dependencies. Subsequently, a heuristic search-based approach is applied to generate test cases. The resulting test cases clearly discriminate between safety critical and normal driving scenarios, with the latter covering a wider spectrum than the former. The verification of the generated test cases proves that the proposed methodology properly accounts for both severity and exposure in the test case generation process. Overall, the current study contributes to fill a gap concerning the specific applicable methodologies capable of accounting for both severity and exposure and calls for further research to prove its applicability in more complex environments and scenarios.

The physiological and behavioral influences of 2.45 GHz microwaves on Drosophila melanogaster were examined. Standing waves transitioned into heat energy effectively when passing through the insect body. On the contrary, travelling waves did not transit into heat energy in the insect body. This indicated that there was no concern regarding the thermal effects of microwave irradiation for levels of daily usage. However, we detected genotoxicity and behavioral alterations associated with travelling wave irradiation, which can be attributed to the non-thermal effects of the waves. Electron spin resonance (ESR) revealed that fruit flies possessed paramagnetic substances in the body such as Fe3+, Cu2+, Mn2+, and organic radicals. The temperature dependent intensities of these paramagnetic substances indicated that females possessed more of the components susceptible to electromagnetic waves than males, and the behavioral tests supported the differences between the sexes.

The objective of this study was to evaluate rebound characteristics for running-specific prostheses by quantifying their dynamic behavior by an impact experiment. The impact experiment was conducted to produce a typical ground foot strike contact, and to obtain the dynamic behavior of blades during and after impact. The motion of the impactor and displacement of the blade was quantified by tracking markers attached to the surface of the impactor and blade using the digital image correlation method. Impact load was also calculated using the history of acceleration. An average spring stiffness, which was obtained by dividing the maximum impact load by its displacement, was proposed to evaluate the rebound characteristics for prostheses. As a result, the difference between the types of blades can be observed using the proposed stiffness and velocity ratio. This relationship indicates that the stiffness and the ratio may have the potential to be applicable to evaluate the performance of blades.

Ultrasonic wave-sensing technology has been applied for the health monitoring of composite structures, using normal fiber Bragg grating (FBG) sensors with a high-speed wavelength interrogation system of arrayed waveguide grating (AWG) filters; however, researchers are required to average thousands of repeated measurements to distinguish significant signals. To resolve this bottleneck problem, this study established a signal-processing strategy that improves the signal-to-noise ratio for the one-time measured signal of ultrasonic waves, by application of parallel factor analysis (PARAFAC) technology that produces unique multiway decomposition without additional orthogonal or independent constraints. Through bandpass processing of the AWG filter and complex wavelet transforms, ultrasonic wave signals are preprocessed as time, phase, and frequency profiles, and then decomposed into a series of conceptual three-way atoms by PARAFAC. While an ultrasonic wave results in a Bragg wavelength shift, antiphase fluctuations can be observed at two adjacent AWG ports. Thereby, concentrating on antiphase features among the three-way atoms, a fitting atom can be chosen and then restored to three-way profiles as a final result. An experimental study has revealed that the final result is consistent with the conventional 1024-data averaging signal, and relative error evaluation has indicated that the signal-to-noise ratio of ultrasonic waves can be significantly improved.

Background: One of the current problems in the field of metabolomics is the difficulty in integrating data collected using different equipment at different facilities, because many metabolomic methods have been developed independently and are unique to each laboratory. Methods: In this study, we examined whether different analytical methods among 12 different laboratories provided comparable relative quantification data for certain metabolites. Identical samples extracted from two cell lines (HT-29 and AsPc-1) were distributed to each facility, and hydrophilic and hydrophobic metabolite analyses were performed using the daily routine protocols of each laboratory. Results: The results indicate that there was no difference in the relative quantitative data (HT-29/AsPc-1) for about half of the measured metabolites among the laboratories and assay methods. Data review also revealed that errors in relative quantification were derived from issues such as erroneous peak identification, insufficient peak separation, a difference in detection sensitivity, derivatization reactions, and extraction solvent interference. Conclusion: The results indicated that relative quantification data obtained at different facilities and at different times would be integrated and compared by using a reference materials shared for data normalization.

A lantern-type diruthenium(II,III) complex [Ru2(HNOCPh)4(BF4)(H2O)] was prepared from [Ru2(HNOCPh)4Cl]n by removal of the axial chlorido-bridge using AgBF4 in THF. The room temperature magnetic moment (per Ru25+ unit) of [Ru2(HNOCPh)4(BF4)(H2O)] is 3.84 μB, which is similar to that (4.15 μB) of [Ru2(HNOCPh)4Cl]n, for which magnetic measurement was newly performed in this study. These results indicate that both of the complexes have a spin state of S = 3/2, although temperature-variable (VT) magnetic moments (2–300 K) showed that considerable antiferromagnetic interaction (zJ = −2.8 cm−1) exists through the axial chlorido-bridge for [Ru2(HNOCPh)4Cl]n, but such a large interaction (zJ = −0.08 cm−1) does not exist for [Ru2(HNOCPh)4(BF4)(H2O)], where the large zero-field splitting D = 61 cm−1 is operative for both complexes, like other lantern-type diruthenium(II,III) complexes. The X-ray single-crystal structure analysis of [Ru2(HNOCPh)4(BF4)(H2O)]·2(acetone) showed that the axial positions of the complex were occupied by a fluorine atom of the BF4− ion and an oxygen atom of the water molecule, with distances of Ru-Fax = 2.3265(19) Å and Ru-Oax = 2.280(2) Å, respectively. The Ru-Ru bond distance was 2.2793(4) Å, which is shorter than those (2.295(2) and 2.290(2) Å) reported for [Ru2(HNOCPh)4Cl]n. The quartet ground states (S = 3/2) were reasonably interpreted for [Ru2(HNOCPh)4(BF4)(H2O)] and [Ru2(HNOCPh)4Cl]n, as well as the theoretically modeled complex cation [Ru2(HNOCPh)4]+, by DFT calculation results. A Ru26+/Ru25+ redox couple was observed at 1.12 V (vs. SCE) for [Ru2(HNOCPh)4(BF4)(H2O)] in dichloromethane containing Bu4NPF6 as electrolyte.