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Albuminuria is a major risk factor of cardiovascular events, however, the impact of albuminuria on clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) has not been fully investigated. This retrospective study included 206 patients who underwent TAVR for severe aortic stenosis. Patients were divided into two groups according to the preoperative urinary albumin-to-creatinine ratio (ACR): high (ACR ≥ 30 mg/g) and low (ACR30 mg/g). The incidence of 1-month worsening renal function (WRF), defined as a decrease in estimated glomerular filtration rate (eGFR) ≥10% from baseline after TAVR, was investigated. Patients with high ACR had acute kidney injury (8.5% vs. 1.0%, p = 0.01) and 1-month WRF (29.2% vs. 12.0%, p = 0.002) more frequently than those with low ACR. High ACR was independently associated with 1-month WRF (odds ratio, 3.72; 95% confidence interval, 1.72-8.08; p0.001). Albuminuria can be a useful predictor of deterioration of renal function at various time points after TAVR.

The relationship between carotid artery ultrasound findings and clinical outcomes in patients who undergo percutaneous coronary intervention (PCI) has not been completely elucidated.This single-center retrospective study investigated 691 patients who underwent PCI and carotid ultrasound testing. Maximum carotid intima-media thickness (CIMT) was defined as the greatest CIMT at the maximally thick point among the common carotid artery, carotid bulb, and internal carotid artery. A carotid plaque was defined as vessel wall thickening with a CIMT ≥ 1.5 mm. The characteristics of carotid plaque (heterogeneity, calcification, or irregular/ulcerated surface) were evaluated visually. Patients were divided into those with and without heterogeneous carotid plaque (maximum CIMT ≥ 1.5 mm and heterogeneous texture). The endpoint was the incidence of a major adverse cardiovascular event (MACE) defined as a composite of cardiovascular (CV) death, myocardial infarction, and ischemic stroke.Among 691 patients, 309 were categorized as having a heterogeneous plaque. Patients with heterogeneous plaques were at a higher risk of MACE than those without (p=0.002). A heterogeneous plaque was independently associated with MACE after adjusting for covariates (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.01-2.90; p=0.046). Calcified or irregular/ulcerated plaques were correlated with a higher incidence of MACE, but both were not independently associated with MACE (HR, 1.35; 95% CI, 0.69-2.64, p=0.38 and HR, 0.98; 95% CI, 0.57-1.69; p=0.95, respectively).The presence of a heterogeneous carotid plaque in patients who underwent PCI predicted future CV events. These patients may require more aggressive medical therapy and careful follow-up.

Objective The relationship between cardiovascular disease and the serum polyunsaturated fatty acid parameters has been reported. The aim of the present study was to investigate the association between the eicosapentaenoic acid and arachidonic acid (EPA/AA) ratio and long-term cardiovascular events in patients with coronary artery disease. Methods We identified a total of 831 patients who underwent percutaneous coronary intervention and whose EPA/AA ratio was available. The patients were divided into two groups according to their serum EPA/AA ratio (median, 0.29; interquartile range 0.19-0.47): those in the lower quartile of EPA/AA ratios (Low EPA/AA group; n=231) and all other subjects (High EPA/AA group; n=600). The primary endpoints included a composite of cardiovascular death, myocardial infarction, and ischemic stroke. Results Patients in the Low EPA/AA group were significantly younger (66.0±12.6 years vs. 69.9±9.3 years, p

Future embedded systems and services will be seamlessly connected and will interact on all levels with the infrastructure and cloud. For safety-critical applications this means that it is not sufficient to ensure dependability in a single embedded system, but it is necessary to cover the complete service chain including all involved embedded systems as well as involved services running in the edge or the cloud. However, for the development of such Cyber-Physical Systems-of-Systems (CPSoS) engineers must consider all kinds of dependability requirements. For example, it is not an option to ensure safety by impeding reliability or availability requirements. In fact, it is the engineers’ task to optimize the CPSoS’ performance without violating any safety goals.

Co-working and interaction of automated systems and humans in a warehouse is a significant challenge of progressing industrial systems’ autonomy. Especially, blind corners pose a critical scenario, in which infrastructure-based sensors can provide more safety. The automation of vehicles is usually tied to an argument on improved safety. However, current standards still rely on the awareness of humans to avoid collisions, which is limited at corners with occlusion. Based on the examination of blind corner scenarios in a warehouse, we derive the relevant critical situations. We propose an architecture that uses infrastructure sensors to prevent human-robot collisions at blind corners with respect to automated forklifts. This includes a safety critical function using wireless communication, which sporadically might be unavailable or disturbed. Therefore, the proposed architecture is able to mitigate these faults and gracefully degrades performance if required. Within our extensive evaluation, we use a warehouse simulation to verify our approach and to estimate the impact on an automated forklift’s performance.

Rising automation levels in the automotive domain demand a shift from the fail-safe to the fail-operational paradigm. Fail-operational architectures and behaviors are inherently more complex and thus require special diligence from a safety engineering point of view. In this work, we present how we tailored and applied a methodology that facilitates the design of fail-operational architectures from early design stages on by enabling informed judgment regarding the gradually evolved architecture's fitness for purpose. The method specifically considers resilience regarding dynamic changes in environmental conditions, including V2X aspects and internal capabilities. In this paper, we summarize our experiences in applying the methodology in a highway pilot case study. Furthermore, we present essential extensions of the methodology for modeling and evaluating the operational design domain.

The dimethylamino group of AkaLumine ((4S)-2-[(1E,3E)-4-[4-(dimethylamino)phenyl]-1,3-butadien-1-yl]-4,5-dihydro-4-thiazolecarboxylic acid), a red-light-emitting firefly luciferin analogue, was replaced by cyclic amino groups (1-pyrrolidinyl, 1-piperidino, 1-azepanyl, and 4-morpholino) to give AkaLumine analogues exhibiting desirable bioluminescence with emission maxima in the red region (656–667 nm). In particular, a bioluminescence reaction of 1-pyrrolidinyl analogue with a recombinant Photinus pyralis luciferase showed a higher quantum yield than that with AkaLumine, giving an improved bioluminescence intensity. The 1-pyrrolidinyl analogue also showed the strongest luminescence in whole-body luciferase-expressing mice among the analogues, indicating that a quantum yield improvement of a luciferin analogue is effective to increase bioluminescence imaging intensity.

Increasing evidence indicates that many insecticides produce significant epigenetic changes during embryogenesis, leading to developmental toxicities. However, the effects of insecticides on DNA methylation status during early development have not been well studied. We developed a novel nuclear phenotypic approach using mouse embryonic stem cells harboring enhanced green fluorescent protein fused with methyl CpG-binding protein to evaluate global DNA methylation changes via high-content imaging analysis. Exposure to imidacloprid, carbaryl, and o,p'-DDT increased the fluorescent intensity of granules in the nuclei, indicating global DNA methylating effects. However, DNA methylation profiling in cell-cycle-related genes, such as Cdkn2a, Dapk1, Cdh1, Mlh1, Timp3, and Rarb, decreased in imidacloprid treatments, suggesting the potential influence of DNA methylation patterns on cell differentiation. We developed a rapid method for evaluating global DNA methylation and used this approach to show that insecticides pose risks of developmental toxicity through DNA methylation.

LiF-NiO composites in a molar ratio of 1:1 are synthesized by the mechanical milling of equal amounts of LiF and NiO for 12–144 h. The synthesized composites are investigated by XRD, charge-discharge measurements, and XPS. The XRD peaks of NiO broaden with an increase in the milling time, while those of LiF disappear. Rietveld analysis shows that the LiF-NiO composites prepared by milling for more than 72 h form a solid solution and that the arrangement of Li + and Ni 2+ ions in them is disordered. The LiF and NiO samples milled individually do not exhibit a noticeable discharge capacity, while the composites show a large one. Further, the discharge capacity of the LiF-NiO composites increases with the milling time, with the composite prepared by milling for 144 h exhibiting a discharge capacity of 216 mA h g −1 and an average voltage of 3.53 V at 0.05 C for voltages of 2.0–5.0 V. The XPS data suggest that the Ni ions are probably oxidized and reduced repeatedly during the charge-discharge process and that the Ni 2+ ions are partially oxidized to Ni 3+ ions during charging to 5.0 V.

An autonomous driving system requires the safety and availability of automated driving. For example, an autonomous driving system with automation level 3 requires the functions to request the driver to take over driving and to sustain safe automated driving until the driver accepts the request if a hardware failure occurs. However, there is a demand to continue automated driving if the system maintains sufficient performance for automated driving after the failure occurs. Therefore, we propose a graceful degradation design process to improve the automated driving continuation rate by defining degradation functions against performance limitation and hardware failure. The process integrates and extends ISO/PAS 21448 and ISO26262 and carries out these tasks in the order of system-level, ECU-level, and microcontroller-level degradation design. Furthermore, we propose a framework to calculate worst-case mode switch time (WCMST), which means the time duration from failure detection to degradation processing, by utilizing degradation design results. To evaluate the proposed process and framework, we applied them to the prototype system with automation level 3. The evaluation results showed that the designed system can sustain automated driving against 86.1% of performance degradation factors and that the framework can improve the calculation accuracy of WCMST by 35.3%.

Piceatannol (3,3',4',5-trans-tetrahydroxystilbene) is a polyphenolic compound abundant in the seeds of passion fruit (Passiflora edulis). Piceatannol is an analogue of resveratrol (3,4',5-trans-trihydroxystilbene) and shares the structural motif and biological activities such as activation of SIRT1. Several studies have shown that piceatannol is more potent than resveratrol. In this study, we examined the effects of piceatannol on neural stem cell differentiation into astrocytes compared with those of resveratrol. At a concentration of 2.5 μM, piceatannol promoted astrocyte differentiation, while resveratrol had no effect at this concentration. Furthermore, we found that oral administration of piceatannol increased the number of astrocytes in the brains of adult mice, while resveratrol administration showed no effects. These results suggest that piceatannol has a superior effect to resveratrol in promoting astrocyte differentiation.

Sameuramide A (1), a new cyclic depsipeptide encompassing one each of alanine, N-methyl alanine, N-methyl dehydroalanine, N,O-dimethyl threonine, phenyllactic acid, three β-hydroxy leucines, and two propionates, was isolated from a didemnid ascidian collected at the northern part of Japan. The planar structure was established based on the interpretation of MS and NMR data. The absolute configuration of the subunits was determined by the advanced Marfey's method and the chiral LC-MS analysis. Compound 1 exhibited the activity of maintaining colony formation of murine embryonic stem (mES) cells without leukemia inhibitory factor (LIF). Down regulation of the gene expression of Kruppel-like transcription factor 4 (Klf4) indicated that 1 itself was not able to maintain the undifferentiated state of the mES cells. However, the expression levels of the marker genes (Nestin, T, Sox17) for three germ layers were upregulated in embryoid bodies (EBs) after treatment of 1 together with LIF, suggesting that 1 plays a supportive role for LIF in maintaining the multipotency of mES cells.

We present an evacuation behavior simulation system at the time of tsunami using the evacuation agent of a game engine. The tsunami evacuation behavior simulation system is a system that enables local governments and residents to work together to formulate disaster prevention plans. As a representation of a simple tsunami, in this system, a slightly oblique plane is inserted as the sea surface to a three-dimensional model of the terrain, building, and road, which is generated by geographical information system data. Mass agents of evacuees randomly placed on the road will move toward the nearest wide evacuation shelter or tsunami evacuation building. As a result, problems were found in the shape of some roads and the position of evacuation buildings.

Highly automated and autonomous driving is a major trend and vast amounts of effort and resources are presently being invested in the development of corresponding solutions. However, safety assurance is a concern, as established safety engineering standards and methodologies are not sufficient in this context. In this paper, we elaborate the fundamental safety engineering steps that are necessary to create safe vehicles of higher automation levels. Furthermore, we map these steps to the guidance presently available in existing (e.g., ISO26262) and upcoming (e.g., ISO PAS 21448) standards and point out open gaps. We then outline an approach for overcoming the identified deficiencies by integrating three different safety engineering disciplines. This includes (1) creating a safe nominal behavior specification; (2) dealing with functional insufficiencies, and (3) assuring the related performance wrt. functional safety. We exemplify our proposed methodology with a case study from industry.

Brain-derived neurotrophic factor (BDNF) plays a fundamental role in expressing various neural functions including memory consolidation. Alterations of BDNF levels in the brain are associated with neurodegenerative and neuropsychiatric disorders. Therefore, it is important to understand how levels of BDNF are controlled. Recently we generated a novel transgenic mouse strain, termed the Bdnf-Luciferase transgenic (Bdnf-Luc Tg) mouse, to monitor changes in Bdnf expression. In the present study, we detected the bioluminescence signal from living Bdnf-Luc Tg mice after intraperitoneal administration of d-luciferin. Despite high levels of Bdnf expression in the brain, it was difficult to detect a signal from the brain region, probably because of its poorly penetrable (short-wavelength) bioluminescence. However, we could detect the changes in the bioluminescence signal in the brain region using a luciferin analogue generating a near-infrared wavelength of bioluminescence. We also found a strong correlation between increases in body weight and bioluminescence signal in the abdominal region of Tg mice fed a high-fat diet. These results show that changes in Bdnf expression can be visualized using living mice, and that the Tg mouse could be a powerful tool for clarification of the role of Bdnf expression in pathophysiological and physiological conditions.

A bio-inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1-substituted derivatives. This cascade features a 2-aminoimidazole formation that is modeled after an arginine post-translational modification and an aza-electrocyclization. It can be effectively carried out in a one-pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible. We found that some compounds out of this structurally novel library show a significant activity in modulating the neural differentiation. Namely, these compounds selectively activate or inhibit the differentiation of neural stem cells to neurons, while being negligible in the differentiation to astrocytes. This study represents a successful case in which the native biofunction of a natural product could be altered by structural modifications.

Corrosion and Mechanical properties of a recycled 5083 aluminum alloy by solid state recycling have been compared with those of a virgin extrusion which was processed from the ingot block. In the solid state recycling, the machined chips were extruded at 723 K with an extrusion ratio of 44 : 1 in air. As a result of the salt immersion tests, the mass loss of the solid recycled specimen was not less than twice of that of the virgin extruded specimen. The deterioration in corrosion properties for the solid recycled specimen was attributed to the excessive contamination of iron which promoted galvanic corrosion. As a result of tensile tests, the solid recycled specimen exhibited a good combination of high strength and high elongation to failure at room temperature. The excellent mechanical properties for the solid recycled specimen were attributed to the refined microstructure. However, the elongation to failure of the solid recycled specimen at elevated temperatures more than 573 K was lower than that of the virgin extruded specimen. The contamination of oxide particles is likely to be responsible for the lower elongation in the solid recycled specimen.

In ITER, austenitic stainless steels are under consideration as a blanket structural material for temperature below 200°C. Transmuted helium will be also produced in austenitic stainless steels by high-energy neutron irradiation, and it will affect microstructural development including grain boundary segregation. In this paper, the effects of helium on grain boundary segregation in austenitic stainless steels are studied using ion-irradiation experiment. The result showed that the onset of radiation induced segregation (RIS) by proton irradiation occurs somewhere between 0.1 and 0.5 dpa. Helium pre-implantation significantly reduced RIS of the major alloying elements. Mechanisms are discussed. Comparison of this result with neutron irradiated induced segregation showed qualitative agreement in the data trends. However, a large amount of segregation was observed in the proton irradiated 304 austenitic stainless steels specimens.

A mouse cDNA encoding paired-box-containing gene (Pax-4) was cloned from a cDNA library of a mouse pancreatic islet β cell line of MIN6. The predicted open reading frame encodes a protein of 349 amino acids with a calculated molecular weight (MW) of 38-kD. A human Pax-4 cDNA sequence encoding 350 amino acids was deduced from a human cosmid clone. The mouse nucleotide and deduced amino acid sequences exhibit 83.4 and 80.0% identity with those of deduced human Pax-4, respectively. Southern blot analysis suggested that the mouse Pax-4 gene exists as a single copy in the genome. Reverse transcription (RT)-PCR analysis suggested that the mouse Pax-4 gene is expressed in pancreatic islets, cultured islet β cell lines of MIN6, βTC, and NIT-1 cells, but not detectable in any of 13 adult mouse organs examined.

今回われわれは直腸平滑筋腫の1例を経験したので報告する.症例は66歳の女性, 肛門部不快感, 下血を主訴に入院した.注腸造影, 直腸鏡, 骨盤computed tomography, magnetic resonance imagingなどの検査により直腸粘膜下腫瘍 (平滑筋腫疑い) と診断し手術を施行した.全身麻酔下に経仙骨的に腫瘍に達し, 腫瘍を摘出した.摘出標本は4.0×4.0×5.2cmの白色の充実性腫瘍で2.0×3.0×3.0cmのdaughter noduleと一塊になっていた.病理組織学的に平滑筋腫と診断された.直腸平滑筋腫はその良性悪性の鑑別が時に困難で, 悪性化例も報告されており, 慎重な術後経過観察を要するものと思われた.

A cDNA clone encoding a human ribosomal protein L39 (hRPL39) was isolated through a random cDNA sequencing approach to a cDNA library constructed from a human colon carcinoma cell line of COLO 205. Although levels of hRPL39 mRNA were different in several cell lines including carcinoma cell lines from different tissues, they were shown not to be cell cycle-dependent in a human fibroblast cell line of TIG-1.

Insulin-dependent diabetes mellitus (IDDM, type I diabetes) is an autoimmune disease resulting from autoimmune destruction of pancreatic islet B-cells. The models of human IDDM, non-obese diabetic (NOD) mice and Bio Breeding (BB) rats, have provided a large amount of information on the pathogenesis of IDDM. In these animal models, immune cells, which include helper T (CD4+) and cytotoxic T (CD8+) lymphocytes, B-lymphocytes, and macrophages, infiltrate pancreatic islets (insulitis) preceding islet B-cell destruction, with consequent overt diabetes and ketosis. Insulitis and diabetes in NOD mice or BB rats can be induced by adoptive transfer of lymphocytes and can be prevented by the immunosuppressive agents. Thus, insulitis and the consequent diabetes in NOD mice are caused by the cell-mediated organ-specific autoimmune mechanism. Although it is clear that the destructive process of islet B-cells requires both CD4+ and CD8+ T-cell subsets, the relative contribution of each subset in provoking diabetes is uncertain.