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In recent years, ultra-compact electric vehicles have gained increasing interest. These vehicles can easily make turns owing to their compactness, and they have a low impact on the environment. However, exterior road and wind noises have a large impact on occupant comfort in the interior space because an electric motor is used instead of an internal combustion engine. Therefore, an active noise control system using control sound or masking for ultra-compact electric vehicles was studied. To select the sound used for masking, a sound containing 1/f fluctuation, which has a relaxing effect on humans, was investigated. In the study of 1/f fluctuations, various analysis methods for comfort evaluation are used. However, a method of detecting sounds including 1/f fluctuations has not been established and clarified. Thus, a basic study of 1/f fluctuations was performed to select the sound to be used for the masker. Furthermore, brain waves of participants were measured in cases in which participants heard sounds including or not 1/f fluctuation. The results revealed that sounds including 1/f fluctuation of amplitude and frequency helped participants to relax.

Although excess production of androgens and glucocorticoids has often been observed in adrenocortical carcinomas, adrenocortical adenoma with such hormonal activity is rare. Herein, we report a 41-year-old woman who presented with hyperandrogenemia and mild autonomous cortisol secretion with an undetectable level of adrenocorticotropic hormone. Imaging demonstrated a 6 cm left adrenal tumor. The histologic diagnosis of the resected adrenal tumor was adrenocortical adenoma. Pre- and post-operative serum samples were used for steroid profiling with liquid chromatography-tandem mass spectrometry (LC-MS/MS). LC-MS/MS analysis of pre-operative serum revealed an abnormal buildup of steroid precursors and androgens. Importantly, circulating levels of 11-oxygenated androgens, including 11β-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT), were highly elevated. Both androgen and glucocorticoid levels significantly decreased post-operatively. Immunohistochemical analysis of steroidogenic enzymes and cofactor protein supported the tumor's ability to directly produce 11OHT and 11KT. This study is the first to describe and characterize an adrenocortical adenoma that co-secretes glucocorticoids and 11-oxygenated androgens. Significance statement Due to its rarity, biochemical and histologic characteristics of androgen and glucocorticoid co-secreting adrenocortical adenomas are largely unknown. Herein, we report a case of adrenocortical adenoma that caused marked hyperandrogenemia and mild autonomous cortisol secretion. In this study, we investigated serum steroid profiles using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and histologic characteristics of the resected tumor. LC-MS/MS revealed highly elevated levels of 11-oxygenated androgens which have not been well studied in adrenal tumors. The expression patterns of steroidogenic enzymes determined by immunohistochemistry supported the results of steroid profiling and suggested the capacity of the tumor cells to produce 11-oxygenated androgens. Measurement of 11-oxygenated steroids should facilitate a better understanding of androgen-producing adrenocortical neoplasms.

Purpose To evaluate left atrial (LA) function in patients with hypertrophic cardiomyopathy (HCM) by LA strain assessment using cardiac computed tomography (CT-derived LA strain). Materials and methods This was a retrospective study of 34 patients with HCM and 31 non-HCM patients who underwent cardiac computed tomography (CT) using retrospective electrocardiogram-gated mode. CT images were reconstructed every 5% (0–95%) of the RR intervals. CT-derived LA strain (reservoir [LASr], conduit [LASc], and booster pump strain [LASp]) were semi-automatically analyzed using a dedicated workstation. We also measured the left atrial volume index (LAVI) and left ventricular longitudinal strain (LVLS) for the left atrial and ventricular functional parameters to assess the relationship with CT-derived LA strain. Results CT-derived LA strain significantly correlated with LAVI: r = − 0.69, p r = − 0.70, p r = − 0.35, p = 0.004 for LASc. CT-derived LA strain also significantly correlated with LVLS: r = − 0.62, p r = − 0.67, p r = − 0.42, p = 0.013 for LASp. CT-derived LA strain in patients with HCM was significantly lower than that in non-HCM patients: LASr (20.8 ± 7.6 vs. 31.7 ± 6.1%, p p p Conclusion CT-derived LA strain is feasible for quantitative assessment of left atrial function in patients with HCM.

The purpose of this study was to investigate the effects of neck and shoulder pain (NSP) and the position of the head and neck on the intramuscular circulation of the cervical muscles such as the trapezius and levator scapulae muscles in young females. Ten NSP subjects (mean age: 20.9 ± 0.5 years) and ten non-NSP subjects (mean age: 20.6 ± 0.7 years) were recruited to this study. Near-infrared spectroscopy (NIRS) was used to non-invasively measure total haemoglobin (Total-Hb), oxygenated haemoglobin (Oxy-Hb), and deoxygenated haemoglobin (Deoxy-Hb) of the trapezius and levator scapulae muscles. The measurements of Total-Hb, Oxy-Hb, and Deoxy-Hb were taken in the neutral position, immediately after the maximally flexed (extended) position, and after 30 s in the maximally flexed (extended) position. In flexion, no significant main effect or interaction was observed with Total-Hb and Oxy-Hb. A significant interaction was observed with Deoxy-Hb (p 0.01). There was no significant difference in the changes over time in the NSP group (p = 0.91). However, in the non-NSP group, a significant increase was noted at the neutral position to immediately after the maximally flexed position (p 0.01) and at the end of maintaining the maximally flexed position (p 0.01). In extension, no significant main effect or interaction was observed with Total-Hb and Oxy-Hb. A significant interaction was observed with Deoxy-Hb (p 0.01). In the NSP group, no significant difference was observed in the changes over time (p = 0.91). In the non-NSP group, however, a significant decrease was observed from the neutral position to immediately after the maximally extended position (p 0.01). The results of this study indicate that maintaining either maximal cervical flexion or extension may affect venous blood flow on non-NSP group. However, no effect on NSP group was observed due to existing diminished intramuscular circulation.

A deficiency in lumbar muscle blood circulation is considered to be a major risk factor for non-specific low back pain. The aim of this study was to investigate changes in relative circulation over time in the lumbar multifidus in different positions on sitting.Twelve healthy subjects (7 males, 5 females, average age: 20.9 years) without low back pain for the past 12 months were recruited. Near-infrared spectroscopy (NIRS) was used to non-invasively measure total haemoglobin (Total-Hb) and oxygenated haemoglobin (Oxy-Hb) in the lumbar multifidus at the L5-S1 segment. Subjects were asked to move into either 60-degree trunk-flexed or 20-degree trunk-extended position from the starting (standing in neutral) position in 3 s, timed by a metronome, and to maintain these positions for 30 s. The measurements of Total-Hb and Oxy-Hb were compared at -3 (neutral position), 0, 10, 20, and 30 s in each flexed and extended position on sitting.In flexion, Total-Hb and Oxy-Hb of the lumbar multifidus were significantly decreased from a neutral (-3 s) to flexed (0 s) position (Total-Hb: p = 0.002, Oxy-Hb: p = 0.004); however, there were no significant differences in the flexed position. In extension, Total-Hb and Oxy-Hb of the lumbar multifidus were significantly increased from 0 to 10 s (Total-Hb: p 0.001, Oxy-Hb: p 0.001); however, there were no significant differences from the neutral (-3 s) to extended (0 s) position, or from 10 to 30 s.The results of this study indicate that the intramuscular circulation of the lumbar multifidus decreases immediately once the trunk starts moving into a flexed position on sitting. On the other hand, the intramuscular circulation of the lumbar multifidus increases for up to 10 s once the trunk starts moving into an extended position.

[Purpose] The characteristics of neck and shoulder pain (NSP) in different age populations have not been sufficiently examined. Therefore, the purpose of this study was to compare and verify the cervicothoracic spinal alignment and neck flexor muscle endurance of young and older adult females with and without NSP. [Participants and Methods] We assessed 72 female participants (39 young participants, 33 elderly participants, 43 NSP, 29 non-NSP) aged 18-82 years who were recruited for this study. Cervicothoracic spinal alignment measurements were obtained with forward head alignment (FHA) along with the upper thoracic angle. The neck flexor endurance test was performed. [Results] There were no significant age-by-group interactions for any of the assessment variables. However, the upper thoracic angle and neck flexor muscle endurance showed significant effects in the groups. Age also had significant effects on FHA and upper thoracic angle. [Conclusion] These results suggested that the neck flexor muscle endurance was more appropriate as an evaluation tool for older adult females with NSP. It was also suggested that the cervical flexor muscle endurance and upper thoracic angle were more appropriate as evaluation tools for young adult females with NSP.

The yeast protein Mpo1 belongs to a protein family that is widely conserved in bacteria, fungi, protozoa, and plants, and is the only protein of this family whose function has so far been elucidated. Mpo1 is an Fe2+-dependent dioxygenase that catalyzes the alpha-oxidation reaction of 2-hydroxy (2-OH) long-chain FAs (LCFAs) produced in the degradation pathway of the long-chain base phytosphingosine. However, several biochemical characteristics of Mpo1, such as its catalytic residues, membrane topology, and substrate specificity, remain unclear. Here, we report that yeast Mpo1 contains two transmembrane domains and that both its N- and C-terminal regions are exposed to the cytosol. Mutational analyses revealed that three histidine residues conserved in the Mpo1 family are especially important for Mpo1 activity, suggesting that they may be responsible for the formation of coordinate bonds with Fe2+. We found that, in addition to activity toward 2-OH LCFAs, Mpo1 also exhibits activity toward 2-OH very-long-chain FAs derived from the FA moiety of sphingolipids. These results indicate that Mpo1 is involved in the metabolism of long-chain to very-long-chain 2-OH FAs produced in different pathways. We noted that the growth ofmpo1 Delta cells is delayed upon carbon deprivation, suggesting that the Mpo1-mediated conversion of 2-OH FAs to nonhydroxy FAs is important for utilizing 2-OH FAs as a carbon source under carbon starvation. Our findings help to elucidate the as yet unknown functions and activities of other Mpo1 family members.

Recent clinical practice guidelines for chronic pain indicate, with a high evidence level, that the combination of exercise and cognitive behavioral therapy (CBT) is effective. The purpose of this study was to evaluate the effectiveness of an exercise facilitation method in combination with CBT using the “Ikiiki Rehabilitation Notebook” for patients with intractable chronic pain. “Ikiiki” means active in Japanese. A total of 22 cases with chronic low back (n = 13), lower extremity (n = 8), or neck (n = 1) pain were treated using this notebook. Two cases dropped out, leaving 22 cases. Each case was evaluated in terms of the numerical rating scale (NRS) of the pain, activities of daily living (ADL), pain catastrophizing scale (PCS), and quality of life (QOL) at pretreatment and post-treatment. The endpoint of the method was to achieve the long-term goals set by the patients. The mean treatment period was 11.2 months. The outcomes were as follows: improvement of presenteeism: nine cases; enhanced participation in hobbies: seven cases; improved school attendance: two cases; return to work: one case; improvement of self-care and/or self-efficacy: three cases. The NRS, ADL, PCS, and QOL were significantly improved after the treatment. This method is possibly valuable for educating patients about the cause and treatment of chronic pain and actively facilitating exercise and social participation. Further studies are needed to investigate the effectiveness of using this notebook for the patient with intractable chronic pain.

A single-time two-point spectral closure is developed by approximation of the Lagrangian direct interaction approximation (LDIA) for a passive scalar in the presence of a mean scalar gradient in homogeneous isotropic turbulence. In the derivation of a single-time two-point spectral closure, the two assumptions, Markovianisation and the exponential form of Lagrangian velocity response function, are made for the LDIA, and angle dependence of the passive-scalar field is expressed by the second-order truncation of Legendre polynomials, in which such a truncation is justified by the linear theory. The resulting closure equations are derived in a straightforward way except for the above assumptions and further simplifications. The closures studied agree qualitatively with direct numerical simulation for one- and two-point statistics of a passive-scalar field in the case of unity Schmidt number. For both direct numerical simulation and closures, we show that the dependence of one-point passive-scalar statistics on the Peclet number based on scalar Taylor microscales collapses properly compared with that based on velocity microscales. We also propose universal scaling laws for second-order scalar structure functions and demonstrate their validity.

Ultra-compact electric vehicles (EVs) have advanced characteristics, such as compactness, light body, and low environmental impact. However, interior noise caused by the road and wind is a serious problem. We propose an active noise control (ANC) system for ultra-compact EVs using a giant magnetostrictive actuator. The proposed ANC system has a two-way interior noise control and achieves both noise reduction and masking, depending on the driver. In this study, we investigated the improvement of interior sound by masking considering 1/f fluctuation, which relaxs drivers by providing ride comfort based on their preference. In addition, we proposed a calculation method for 1/f fluctuation, including masking music by a numerical analysis using a Fourier transform. Furthermore, we conducted a real-time analysis of the music including 1/f fluctuation using the short-time Fourier transform and evaluated the relationship between the 1/f fluctuation of the whole music analysis and the appearance rate of 1/f fluctuation.

A deterministic forcing method and stochastic forcing method are proposed to keep mean turbulence kinetic energy and mean helicity at ideal values. Using the proposed forcing methods, it is shown that characteristics common to energy and helicity dissipation rates, and results of direct numerical simulations, support the joint cascade scenario of energy and helicity.

Kaneda’s (J. Fluid Mech., vol. 107, 1981, pp. 131–145) Lagrangian renormalized approximation was extended to single-time spectral closure under two assumptions: (i) Markovianization and (ii) the Lagrangian velocity response function is expressed by . The unknown functions and are theoretically derived to be consistent with the exact short-time behaviour of and the asymptotic short-time behaviour of assumed exponential form of , i.e. the present closure is derived from the Navier–Stokes equation without introduction of any adjustable parameters and it can calculate the statistical quantities by theory. The results show that the present closure has good agreement with direct numerical simulation for single- and two-point statistics.

Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjögren-Larsson syndrome (SLS) is one such disorder, which is caused by mutations in the fatty aldehyde dehydrogenase ALDH3A2. To date, the molecular mechanism underlying SLS pathology has remained unknown. In this study, we found that Aldh3a2 is expressed in oligodendrocytes and neurons in the mouse brain, and neurons of Aldh3a2 knockout (KO) mice exhibited impaired metabolism of the long-chain base, a component of sphingolipids. Aldh3a2 KO mice showed several abnormalities corresponding to SLS symptoms in behavioral tests, including increased paw slips on a balance beam and light-induced anxiety. In their brain tissue, 2-hydroxygalactosylceramide, an important lipid for myelin function and maintenance, was reduced by the inactivation of fatty acid 2-hydroxylase. Our findings provide important new insights into the molecular mechanisms responsible for neural pathogenesis caused by lipid metabolism abnormalities.-Kanetake, T., Sassa, T., Nojiri, K., Sawai, M., Hattori, S., Miyakawa, T., Kitamura, T., Kihara, A. Neural symptoms in a gene knockout mouse model of Sjögren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide.

A significant improvement in the building stock energy efficiency is imperative to mitigate climate change. Building stock energy models (BSEMs) that employ reference building models are useful for mitigation analysis. However, most existing BSEMs developed for commercial building stock focus on limited building systems and energy conservation measures, and technology deployments are suggested based on simple vintage-driven scenarios. These approaches are insufficient, particularly for regions where improvements to building insulation performances can have a modest impact. This study aims to establish a BSEM framework to overcome this issue and to validate the framework via its application to the Japanese commercial building stock. The framework develops statistical models for estimating the selection probabilities of system alternatives and utilizes them to disaggregate building stocks. A reference building model is developed for each stock segment. The results show that this approach facilitates the use of multiple technological options considering various factors that affect technological deployments, and it also helps estimate the baseline development of building stocks. Furthermore, the developed model well represents the observed distributions in energy use intensity and estimates the aggregated energy consumption of building stocks with a reasonable accuracy. The baseline development was estimated to reduce the CO2 emission by 18% by 2030 from 2013. Efficiency measures can help avoid the increase in electricity demand caused by electrifying the heat source of heating, ventilating, and air-conditioning and water heating systems. The framework could help extend the scope of BSEM application because BSEM development is not information intensive.

Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder whose causative gene encodes the fatty aldehyde dehydrogenase ALDH3A2. To date, the detailed molecular mechanism of the skin pathology of SLS has remained largely unclear. We generated double-knockout (DKO) mice for Aldh3a2 and its homolog Aldh3b2 (a pseudogene in humans). These mice showed hyperkeratosis and reduced fatty aldehyde dehydrogenase activity and skin barrier function. The levels of ω-O-acylceramides (acylceramides), which are specialized ceramides essential for skin barrier function, in the epidermis of DKO mice were about 60% of those in wild-type mice. In the DKO mice, levels of acylceramide precursors (ω-hydroxy ceramides and triglycerides) were increased, suggesting that the final step of acylceramide production was inhibited. A decrease in acylceramide levels was also observed in human immortalized keratinocytes lacking ALDH3A2. Differentiated keratinocytes prepared from the DKO mice exhibited impaired long-chain base metabolism. Based on these results, we propose that the long-chain-base-derived fatty aldehydes that accumulate in DKO mice and SLS patients attack and inhibit the enzyme involved in the final step of acylceramide production. Our findings provide insight into the pathogenesis of the skin symptoms of SLS, i.e., decreased acylceramide production, and its molecular mechanism.

Phytosphingosine (PHS) is the major long-chain base component of sphingolipids in Saccharomyces cerevisiae The PHS metabolic pathway includes a fatty acid (FA) α-oxidation reaction. Recently, we identified the novel protein Mpo1, which is involved in PHS metabolism. However, the details of the FA α-oxidation reaction and the role of Mpo1 in PHS metabolism remained unclear. In the present study, we revealed that Mpo1 is involved in the α-oxidation of 2-hydroxy (2-OH) palmitic acid (C16:0-COOH) in the PHS metabolic pathway. Our in vitro assay revealed that not only the Mpo1-containing membrane fraction but also the soluble fraction was required for the α-oxidation of 2-OH C16:0-COOH. The addition of Fe2+ eliminated the need for the soluble fraction. Purified Mpo1 converted 2-OH C16:0-COOH to C15:0-COOH in the presence of Fe2+, indicating that Mpo1 is the enzyme body responsible for catalyzing the FA α-oxidation reaction. This reaction was also found to require an oxygen molecule. Our findings indicate that Mpo1 catalyzes the FA α-oxidation reaction as 2-OH fatty acid dioxygenase, mediated by iron(IV) peroxide. Although numerous Mpo1 homologs exist in bacteria, fungi, protozoa, and plants, their functions had not yet been clarified. However, our findings suggest that these family members function as dioxygenases.

The interactions between homogeneous turbulence and a planar shock wave are analytically investigated using rapid distortion theory (RDT). Analytical solutions in the solenoidal modes are obtained. Qualitative answers to unsolved questions in a report by Andreopoulos et al. (Annu. Rev. Fluid Mech., vol. 524, 2000, pp. 309–345) are provided within the linear theoretical framework. The results show that the turbulence kinetic energy (TKE) is increased after interaction with a shock wave and that the contributions to the amplification can be interpreted primarily as the combined effect of shock-induced compression, which is a direct consequence of the Rankine–Hugoniot relation, and the nonlinear effect, which is an indirect consequence of the Rankine–Hugoniot relation via the perturbation manner. For initial homogeneous axisymmetric turbulence, the amplification of the TKE depends on the initial degree of anisotropy. Furthermore, the increase in energy at high wavenumbers is confirmed by the one-dimensional spectra. The enstrophy is also increased; its increase is more significant than that of the TKE because of the significant increase in enstrophy at high wavenumbers. The vorticity components perpendicular to the shock-induced compressed direction are amplified more than the parallel vorticity component. These results strongly suggest that a high resolution is needed to obtain accurate results for the turbulence–shock-wave interaction. The integral length scales ($L$) and the Taylor microscales ($\unicode[STIX]{x1D706}$) are decreased for most cases after the interaction. However, $L_{22,3}(=\,L_{33,2})$ and $\unicode[STIX]{x1D706}_{22,3}(=\,\unicode[STIX]{x1D706}_{33,2})$ are amplified. Here, the subscripts 2 and 3 indicate the perpendicular components relative to the shock-induced compressed direction. The dissipation length and TKE dissipation rate are amplified.

The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sjogren Larsson syndrome (SLS). To date, the molecular mechanism underlying the symptoms characterizing SLS has been poorly understood. Using Aldh3a2(-/-) mice, we found here that Aldh3a2 was the major FALDH active in undifferentiated keratinocytes. Long-chain base metabolism was greatly impaired in Aldh3a2(-/-) keratinocytes. Phenotypically, the intercellular spaces were widened in the basal layer of the Aldh3a2(-/-) epidermis due to hyperproliferation of keratinocytes. Furthermore, oxidative stress-induced genes were upregulated in Aldh3a2(-/-) keratinocytes. Upon keratinocyte differentiation, the activity of another FALDH, Aldh3b2, surpassed that of Aldh3a2. As a result, Aldh3a2(-/-) mice were indistinguishable from wild-type mice in terms of their whole epidermis FALDH activity, and their skin barrier function was uncompromised under normal conditions. However, perturbation of the stratum corneum caused increased transepidermal water loss and delayed barrier recovery in Aldh3a2(-/-) mice. In conclusion, Aldh3a2(-/-) mice replicated some aspects of SLS symptoms, especially at the basal layer of the epidermis. Our results suggest that hyperproliferation of keratinocytes via oxidative stress responses may partly contribute to the ichthyosis symptoms of SLS.

To clarify the breakdown mechanism and the conditions leading to the breakdown under non-uniform electric field in air, we studied the details of breakdown characteristics and mechanism in air by using an ultra-high speed measurement system. We clarified that there were two types of breakdown mechanism in air. The one is the channel heating breakdown, and the other is the leader-type channel development breakdown. These breakdown mechanisms are dominated by three conditions: arrival of secondary streamer from high-voltage anode to opposite grounded cathode, channel heating, and leader-type channel initiation. We studied these conditions quantitatively, and revealed the conditions leading to the breakdown, and the breakdown mechanisms in air were classified. Finally, we clarified the factors, e.g. critical instantaneous power for the secondary streamer arrival, dominating these conditions based on the breakdown mechanism under non-uniform electric field in air.

Phytosphingosine (PHS) is the major long-chain base component of sphingolipids in Saccharomyces cerevisiae. The PHS metabolic pathway includes a fatty acid (FA) α-oxidation reaction. Recently, we identified the novel protein Mpo1, which is involved in PHS metabolism. However, the details of the FA α-oxidation reaction and the role of Mpo1 in PHS metabolism remained unclear. In the present study, we revealed that Mpo1 is involved in the α-oxidation of 2-hydroxy (2-OH) palmitic acid (C(16:0)-COOH) in the PHS metabolic pathway. Our in vitro assay revealed that not only the Mpo1-containing membrane fraction but also the soluble fraction was required for the α-oxidation of 2-OH C(16:0)-COOH. The addition of Fe(2+) eliminated the need for the soluble fraction. Purified Mpo1 converted 2-OH C(16:0)-COOH to C(15:0)-COOH in the presence of Fe(2+), indicating that Mpo1 is the enzyme body responsible for catalyzing the FA α-oxidation reaction. This reaction was also found to require an oxygen molecule. Our findings indicate that Mpo1 catalyzes the FA α-oxidation reaction as 2-OH fatty acid dioxygenase, mediated by iron(IV) peroxide. Although numerous Mpo1 homologs exist in bacteria, fungi, protozoa, and plants, their functions had not yet been clarified. However, our findings suggest that these family members function as dioxygenases.