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Epidemiological studies have shown that cigarette smoking increases the risk of Alzheimer disease. However, inconsistent results have been reported regarding the effects of smoking or nicotine on brain amyloid β (Aβ) deposition. In this study, we found that stimulation of the nicotinic acetylcholine receptor (nAChR) increased Aβ production in mouse brains and cultured neuronal cells. nAChR activation triggered the MEK/ERK pathway, which then phosphorylated and stabilized nuclear SP1. Upregulated SP1 acted on two recognition motifs in the BACE1 gene to induce its transcription, resulting in enhanced Aβ production. Mouse brain microdialysis revealed that nAChR agonists increased Aβ levels in the interstitial fluid of the cerebral cortex but caused no delay of Aβ clearance. In vitro assays indicated that nicotine inhibited Aβ aggregation. We also found that nicotine modified the immunoreactivity of anti-Aβ antibodies, possibly through competitive inhibition and Aβ conformation changes. Using anti-Aβ antibody that was carefully selected to avoid these effects, we found that chronic nicotine treatment in Aβ precursor protein knockin mice increased the Aβ content but did not visibly change the aggregated Aβ deposition in the brain. Thus, nicotine influences brain Aβ deposition in the opposite direction, thereby increasing Aβ production and inhibiting Aβ aggregation. • Stimulation of the nAChR enhances BACE1 transcription and augments cellular Aβ production. • BACE1 induction by nAChR activation is mediated through phosphorylation and stabilization of SP1. • Chronic nicotine treatment results in increased Aβ accumulation but no obvious increase in aggregated Aβ deposition in mouse brain. • Nicotine and cotinine inhibit Aβ aggregation. • Nicotine can modify the immunoreactivity of anti-Aβ antibodies. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the perioperative and postoperative incidence of deep vein thrombosis (DVT) and validate the effectiveness of our own preventive treatment protocol for venous thromboembolism (VTE) occurrence in lower extremity arthroplasty patients. The subjects were 1,054 patients (mean age: 74.3 years) who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA) at our institutions between April 2014 and March 2017. We examined the frequencies of pre- and post-operative DVT by lower extremity Doppler images, and the incidence rate at proximal or distal regions as well as that according to preoperative DVT status were evaluated. Preoperative DVT was detected in 6.5% (69 cases) of our cohort and those were located 1.4% (15 cases) at proximal and 5.1% (54 cases) at distal regions. A significantly higher rate of postoperative DVT development was observed in preoperative DVT+ THA patients (P = 0.0075), but not in TKA patients only with a higher tendency (P = 0.56). The overall incidence of DVT up to 2 weeks after surgeries was 27.3% (288 cases); however, the rate in proximal femur regions was suppressed to 2.8% (30 cases), and there was no symptomatic pulmonary thromboembolism (PTE) case. The results demonstrated the importance of regular Doppler examination for early detection of postoperative DVT occurrence and the following immediate treatment initiation. Our own VTE preventive treatment protocol could reduce the development of proximal DVT, and the periodic monitoring as well as prompt treatment might prevent the fatal PTE. osteoarthritis (OA), rheumatoid arthritis (RA). [ABSTRACT FROM AUTHOR]

Although tapered-wedge short stem has been widely employed with its availability for minimally invasive surgeries in total hip arthroplasty (THA), post-operative stress shielding matter remains unresolved in cementless procedures. This study aimed to clarify the most optimal femoral canal contact regions of the stem design taking stress shielding incidence into consideration. This investigation included 60 joints from 60 patients (mean age at operation: 65.9 years), of which follow-up duration after primary THA had been more than 2 years. Frequencies of spot welds, subsidence, and stress shielding were examined 2 years after surgery. The most suitable femoral canal contact regions were evaluated by plain radiograph (2D) and 3D-computed tomography analyses according to Nakata's division for fitting manners. Spot welds were observed in 38 cases (63.3%), and no subsidence case was seen. Respective number of stress shielding cases, based on Engh's classification, categorized as degree 0, 1, and 2, were 2 (3.3%), 31 (51.7%), and 27 (45.0%), while no cases for degree 3 or 4 were found. When assessed by 3D fitting analysis, 27 cases of stress shielding degree 2 were constituted by 13/42 cases of mediolateral (ML) fit, 2/4 cases of flare fit, and 12/14 cases of multi point fit. In 42 cases of ML fitting, stem contact rate of the most proximedial region in stress shielding degree 0 and 1 was significantly higher compared to stress shielding degree 2 cases. Meanwhile, the rates of distal regions were significantly lower or absent in stress shielding degree 0 and 1 cases. The initial fixation of this stem design was very good in our cohort regardless of fitting manners. This study successfully revealed that ML fitting with femoral component, especially the most proximedial calcar site restricted fitting, would be optimal for reducing stress shielding occurrence in cementless short, tapered-wedge stem THA. Thus, the ideal stem contact region should be considered during THA procedures in light of the reduction of stress shielding development. [ABSTRACT FROM AUTHOR]

Introduction: Available evidence on favorable nutritional factors for preventing osteoporosis remains controversial. Considering the recent increases in life expectancy, we investigated the relationship between incident osteoporotic fractures and dietary habits in early and late postmenopausal phase women. Materials and methods: Subjects were Japanese postmenopausal outpatients recruited at a primary care institution in Nagano Prefecture (Nagano Cohort Study). Patients with critical or acute illness or secondary osteoporosis were not included in this study. In total, 1,071 participants were prospectively followed for a mean of 5.8 years. The cohort was divided into early (≤ 70 years) and late (> 70 years) postmenopausal phases based on median age. Dietary nutrient intake was estimated by the food frequency questionnaire method. According to baseline nutrient intake characteristics, we focused on protein/energy and Ca/NaCl intake ratios, which were also divided by the median values. Results: Kaplan–Meier plots revealed a significantly higher occurrence of fractures for the high protein/energy intake group in early postmenopausal subjects (P = 0.009), whereas the low Ca/NaCl intake group in late postmenopausal subjects exhibited a significantly earlier occurrence of fractures (P = 0.002). Multivariate Cox regression uncovered significant independent risks of higher protein/energy (HR 1.35; 95% CI 1.04–1.74) and lower Ca/NaCl (HR 0.79; 95% CI 0.63–0.99) intake ratios for incident osteoporotic fractures in the early and late postmenopausal cohorts, respectively. Conclusion: Distinct dietary risk factors for osteoporotic fractures were identified in early and late postmenopausal phase women. Appropriate nutritional guidance according to patient age will be important for maintaining bone health and quality of life. [ABSTRACT FROM AUTHOR]

Objective: Osteoarthritis (OA) is a common and degenerative joint disorder in the elderly. A greater importance of understanding the relationship between genetic factors and OA prevalence has emerged with population aging. We therefore investigated the associations of several bone disease-related genetic variants with the prevalence of OA and osteoporosis in Japanese elderly women from the Obuse study cohort, which was randomly sampled from a basic town resident registry.Methods and Results: In total, 206 female participants (mean ± standard deviation age: 69.7 ± 11.0 years) who completed OA, bone mineral density, and genotype assessments were included. The number of patients diagnosed as having knee/hip OA and osteoporosis was 59 (28.6%) and 30 (14.6%), respectively. Fisher's exact testing revealed significant relationships between the minor T allele of LDL receptor related protein 5 (LRP5) rs3736228 and the prevalence of knee/hip OA and osteoporosis. The respective odds ratios (ORs) of the TT genotype for knee/hip OA and osteoporosis were 7.28 (95% confidence interval [CI] 2.22-28.08) and 5.24 (95% CI 0.95-26.98). An additional subgroup analysis for knee OA revealed that the frequency of the common C allele of methylenetetrahydrofolate reductase (MTHFR) rs1801133 had a statistically significant protective association with the prevalence of knee OA (OR 0.58, 95% CI 0.35-0.97).Conclusion: In sum, the present study demonstrated significant associations of LRP5 rs3736228 and MTHFR rs1801133 with knee/hip OA and osteoporosis prevalences and knee OA prevalence, respectively, in Japanese elderly women. These results will help further the understanding of OA pathogenesis and related genetic risk factors. [ABSTRACT FROM AUTHOR]

Background: Brain amyloid-β (Aβ) peptide is released into the interstitial fluid (ISF) in a neuronal activity-dependent manner, and Aβ deposition in Alzheimer's disease (AD) is linked to baseline neuronal activity. Although the intrinsic mechanism for Aβ generation remains to be elucidated, interleukin-like epithelial-mesenchymal transition inducer (ILEI) is a candidate for an endogenous Aβ suppressor.Objective: This study aimed to access the mechanism underlying ILEI secretion and its effect on Aβ production in the brain.Methods: ILEI and Aβ levels in the cerebral cortex were monitored using a newly developed ILEI-specific ELISA and in vivo microdialysis in mutant human Aβ precursor protein-knockin mice. ILEI levels in autopsied brains and cerebrospinal fluid (CSF) were measured using ELISA.Results: Extracellular release of ILEI and Aβ was dependent on neuronal activation and specifically on tetanus toxin-sensitive exocytosis of synaptic vesicles. However, simultaneous monitoring of extracellular ILEI and Aβ revealed that a spontaneous fluctuation of ILEI levels appeared to inversely mirror that of Aβ levels. Selective activation and inhibition of synaptic receptors differentially altered these levels. The evoked activation of AMPA-type receptors resulted in opposing changes to ILEI and Aβ levels. Brain ILEI levels were selectively decreased in AD. CSF ILEI concentration correlated with that of Aβ and were reduced in AD and mild cognitive impairment.Conclusion: ILEI and Aβ are released from distinct subpopulations of synaptic terminals in an activity-dependent manner, and ILEI negatively regulates Aβ production in specific synapse types. CSF ILEI might represent a surrogate marker for the accumulation of brain Aβ. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) is the major component of senile plaques in Alzheimer's disease (AD) brains. Senile plaques are generally observed in cerebral cortex (CTX) rather than cerebellum (CBL) in AD patients. However, it is not clear why CBL has less Aβ deposition than CTX. It is very important to elucidate the mechanism of suppressing Aβ deposition in CBL, because it contributes to understanding of not only AD pathogenesis but also prevention and cure of AD. In this study, we explored to figure out the potential mechanism of reducing Aβ deposition in CBL. We observed higher age-dependent elevation of Aβ level in CTX rather than CBL of human APP knock-in AD model mice, although we detected no significant differences in the levels of interstitial fluid Aβ in these brain tissues. These data imply that less Aβ deposition in CBL is due to enhanced Aβ clearance rather than altered Aβ production in CBL. To gain insights into Aβ clearance in CBL, we injected fluorescence-labeled Aβ in brain tissues. Importantly diffusion area of fluorescent Aβ in CBL was roughly six-times larger than that in CTX within 2 h of injection. In addition, injected Aβ area in CBL decreased sharply after 24 h and CBL-injected Aβ was robustly detected in deep cervical lymph nodes (DcLNs). In contrast, diffusion area of fluorescent Aβ in CTX was consistent up to 72 h and CTX-injected Aβ was faintly detected in DcLNs. Our data suggest that enhanced Aβ drainage in association with meningeal lymphatic system is responsible for less Aβ deposition in CBL. • Less Aβ deposition in cerebellum reflects the less amount of Aβ than that in cerebral cortex. • The Aβ production level in cerebellum is equivalent to that in cerebral cortex. • Aβ diffusion and drainage is enhanced in cerebellum compared to cerebral cortex. • Aβ injected in cerebellum is drained into deep cervical lymph nodes much faster than that in cerebral cortex. [ABSTRACT FROM AUTHOR]

Pentosidine (PEN) and carboxymethyl-lysine (CML) are well-recognized advanced glycation end products (AGEs). However, how these AGEs affect the pathophysiology of osteoporosis and osteoporotic fractures remains controversial. This cross-sectional study aimed to investigate the associations of PEN and CML with bone markers, bone mineral density (BMD), and osteoporotic fractures in postmenopausal women from the Nagano Cohort Study. A total of 444 Japanese postmenopausal outpatients (mean ± standard deviation age: 69.8 ± 10.2 years) were enrolled after the exclusion of patients with acute or severe illness or secondary osteoporosis. The relationships among urinary PEN and serum CML levels, various bone markers, lumbar and hip BMD, and prevalent vertebral and long-bone fractures were evaluated. PEN associated significantly with prevalent vertebral fracture after adjustment for other confounders (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.22–2.07; P < 0.001), but not with lumbar BMD. In contrast, a significant negative correlation was found between CML and lumbar BMD (r = − 0.180; P < 0.001), and this relationship was significant after adjustment for confounders (OR 0.84, 95% CI 0.76–0.93; P < 0.01). Although patients with prevalent vertebral fracture had significantly higher CML levels, the association between CML and prevalent vertebral fracture did not reach significance in the multivariate regression model. Both PEN and CML may play important roles in bone health for postmenopausal women, possibly via different mechanisms. [ABSTRACT FROM AUTHOR]

In amphibians, thyrotropin (TSH), corticotropin (ACTH) and prolactin (PRL) are regarded as the major pituitary hormones involved in metamorphosis, their releasing factors being corticotropin-releasing factor (CRF), arginine vasotocin (AVT), and thyrotropin-releasing hormone (TRH), respectively. It is also known that thyrotropes and corticotropes are equipped with CRF type-2 receptor and AVT V1b receptor, respectively. As for PRL cells, information about the type of receptor for TRH (TRHR) through which the action of TRH is mediated to induce the release of PRL is lacking. In order to fill this gap, an attempt was made to characterize the TRHR subtype existing in the PRL cells of the anterior pituitary gland of the bullfrog, Rana catesbeiana . We cloned cDNAs for three types of bullfrog TRHRs, namely TRHR1, TRHR2 and TRHR3, and confirmed that all of them are functional receptors for TRH by means of reporter gene assay. Analyses with semi-quantitative reverse transcription-PCR and in situ hybridization revealed that TRHR3 mRNA is expressed in the anterior lobe and that the signals reside mostly in the PRL cells. It was also noted that the expression levels of TRHR3 mRNA in the anterior pituitary as well as in the PRL cells of metamorphosing tadpoles elevate as metamorphosis progresses. Since the pattern of changes in TRHR3 mRNA levels in the larval pituitary is almost similar to that previously observed in the pituitary PRL mRNA and plasma PRL levels, we provide a view that TRHR3 mediates the action of TRH on the PRL cells to induce the release of PRL that is prerequisite for growth and metamorphosis in amphibians. [ABSTRACT FROM AUTHOR]

Layered materials are known to exhibit a variety of charge-density wave (CDW) phases due to their quasi-two dimensional nature. Of particular interest is the CDW phase in a prototypical layered transition-metal dichalcogenide (TMDC) TiSe2, where the CDW is known to form with commensurate 2a × 2a × 2c structural distortion at T = 200 K (where a and c are the lattice parameters). Recent experimental studies have revealed intriguing aspects of this material as represented by the emergence of superconductivity upon electron doping and possible existence of the excitonic insulator phase, making TiSe2 attractive as a model material for investigation of collective phenomena in TMDC. However, the evolution of the CDW phase at nanometer-scale thickness, at least below 10 monolayers (6 nm), has not been well investigated yet, in particular from transport viewpoints, presumably due to difficulty in fabrication of such ultrathin samples by conventional approaches. Here, we report the transport properties of a few nanometer-thick highly crystalline TiSe2 epitaxial thin films grown on insulating Al2O3 substrates by molecular-beam epitaxy, demonstrating robust CDW transitions down to 5 monolayers (3 nm). We also clarify an interesting aspect of van der Waals epitaxy, a “self-rotational” growth without strain, which should be realized only in a system having a weak substrate-film interaction. [ABSTRACT FROM AUTHOR]

Reinforcing soils with tension resisting elements is an alternative soil improvement technique confirmed by a series of experimental studies. Fiber reinforcement has advantages in increasing the soil strength and improving the stability of geo-structures. In order to describe and assess the effect of fiber inclusions in soils a suitable constitutive equation is necessary with considering different testing conditions (drainage characteristics, density, applied stress, etc.). In this study, the super/subloading yield surface Cam-clay model (SYS Cam-clay) was used to reproduce the experimental results of drained triaxial compression tests performed under different confining pressures with varying initial relative densities of both unreinforced and fiber-reinforced sand. The reproduced results were in good agreement with experimental results. Both simulated and experimental results showed that an increase in fiber content led to decrease in initial stiffness and increase in initial volumetric compression. This was attributed to the lower initial anisotropy of reinforced sand due to the fiber inclusions. Furthermore, the simulation results indicated that the fiber inclusions inhibited the development of anisotropy compared to unreinforced sand. Consequently, a higher peak and post-peak stresses with increased critical state parameter M, and less volumetric expansion at higher strain rates observed in fiber-reinforced sand. [ABSTRACT FROM AUTHOR]

The flexibility of magnetization of isotropic thick-film magnets enabled us to enhance the torque of a millimeter-size motor comprising a multipolar magnetized rotor compared to the torque of a miniaturized motor using an anisotropic Nd-Fe-B sintered magnet. In order to upgrade the torque of the small motor further, an increase in the remanence value of the isotropic films is indispensable. In this study, therefore, we prepared nano-composite Nd-Fe-B thick films by a high-speed PLD (pulsed laser deposition) method with a deposition rate of approximately 40 μm/h. Resultantly, the use of additive (Zr or Nb) was effective to enhance the coercivity value of Nd-Fe-B thick-film magnets with Nd-poor composition, however it was difficult to increase the remanence values. In order to apply the thick films to a micro-rotor, investigation on several experiments related to mechanical property was also carried out. [ABSTRACT FROM AUTHOR]

Organic semiconductors based on small conjugated molecules generally behave as insulators when undoped, but the heterointerfaces of two such materials can show electrical conductivity as large as in a metal. Although charge transfer is commonly invoked to explain the phenomenon, the details of the process and the nature of the interfacial charge carriers remain largely unexplored. Here we use Schottky-gated heterostructures to probe the conducting layer at the interface between rubrene and PDIF-CN2 single crystals. Gate-modulated conductivity measurements demonstrate that interfacial transport is due to electrons, whose mobility exhibits band-like behaviour from room temperature to ~150?K, and remains as high as ~1?cm2?V?1?s?1 at 30?K for the best devices. The electron density decreases linearly with decreasing temperature, an observation that can be explained quantitatively on the basis of the heterostructure band diagram. These results elucidate the electronic structure of rubrene/PDIF-CN2 interfaces and show the potential of Schottky-gated organic heterostructures for the investigation of transport in molecular semiconductors. [ABSTRACT FROM AUTHOR]

Abstract: Dopamine receptors in mammals are known to consist of two D1-like receptors (D1 and D5) and three D2-like receptors (D2, D3 and D4). The aim of this study was to determine the dopamine receptor subtype that mediates the inhibitory action of dopamine on the release of prolactin (PRL) from the amphibian pituitary. Distal lobes of the bullfrog (Rana catesbeiana) were perifused and the amount of PRL released in the effluent medium was measured by means of a homologous enzyme-immunoassay. TRH stimulated the release of PRL from perifused pituitaries. Dopamine suppressed TRH-induced elevation of PRL release. Quinpirole (a D2 receptor agonist) also suppressed the stimulatory effect of TRH on the release of PRL, whereas SKF-38393 (a D1 receptor agonist) exhibited no such an effect. The inhibitory action of dopamine on TRH-induced PRL release from the pituitary was nullified by the addition of L-741,626 (a selective D2 receptor antagonist) to the medium, but not by the addition of SCH-23390 (a selective D1 receptor antagonist). These data indicate that the inhibitory effect of dopamine on TRH-evoked PRL release from the bullfrog pituitary gland is mediated through D2 dopamine receptors. [ABSTRACT FROM AUTHOR]

Abstract: The cDNA encoding D2 dopamine receptor was cloned from the distal lobe of the bullfrog pituitary. The deduced amino acid sequence of the bullfrog D2 dopamine receptor (bfD2A) spanned 444 amino acids and exhibited typical features of those of D2 dopamine receptors cloned in other animals to date. It showed a high similarity of 75–87% with rat, turkey, Xenopus and tilapia counterparts. Further analysis of nucleotide sequence of the cDNA revealed the presence of putative truncated D2 dopamine receptor isoforms, bfD2B and bfD2C, of which nucleotide sequences lacked 12 and 99 nucleotides of the coding region for bfD2A, respectively. The alignment analysis indicated that putative bfD2C isoform was close to D2S subtype cloned in mammals and birds, whereas bfD2A and putative bfD2B isoforms were close to mammalian and avian D2L subtype and homologous to two isoforms of Xenopus. This is the first report of the presence of mRNAs for two D2L-like isoforms and one D2S-like isoform in a single species. The amino acid sequence responsible for producing isoforms is present in the third intracellular loop, which has been shown to play an important role in the coupling with G protein. Accordingly, differences in the mode of coupling with G protein among three isoforms were suggested. The expression of three isoforms mRNA in organs and tissues was analyzed by RT-PCR. In the brain, pars distalis and pars neurointermedia, mRNAs for three isoforms were invariably expressed, whereas only putative bfD2C mRNA was expressed in peripheral organs and tissues. [Copyright &y& Elsevier]

We succeeded in depositing 200- to 300-µm-thick Nd-Fe-B film magnets with (BH)max of approximately 55 kJ/m3 on Fe substrates by the PLD method. In addition, we confirmed that a millimeter-size motor, which was prepared from the obtained film, rotates at 15,160 rpm under a no-load test. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 159(2): 1–6, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20215 [ABSTRACT FROM AUTHOR]

Co-Pt alloy him magnets were prepared by electrodeposition. After annealing as-deposited turns with face-centered-cubic (fcc) crystal structure, the structure of turns with 24 to 50 at.% Co content transformed 1mm disordered fcc phase to ordered face-centered-tetragonal (fct) L10 phase. It was clarified that Co-Pt film magnets with a Co content of 43 at.% have high coercivity of approximately 880 kA/m. [ABSTRACT FROM AUTHOR]

The adsorption and longitudinal diffusion behaviors of a series of hemicyanine dyes to phospholipid vesicle membranes were studied by second-harmonic generation (SHG) and fluorescence spectroscopies. It was observed that the longitudinal diffusion of cationic hemicyanine dyes takes place immediately after the initial adsorption of these dyes to the outer surface of the vesicle membrane. In contrast, hardly any amount of a zwitterionic hemicyanine dye with a sulfonate group diffused across the vesicle membrane within the measurement time (<2000 s). Based on the difference in the time-course responses of SHG and fluorescence spectroscopies for all of the hemicyanine dyes tested, we propose that hydration of the sulfonate group is mainly responsible for the low diffusivity of the zwitterionic hemicyanine dye. [ABSTRACT FROM AUTHOR]

Isotropic Nd-Fe-B thick-film magnets were prepared by a vacuum arc deposition method followed by a pulse-annealing process. This paper reports the effect of discharge energy of the arc deposition on the magnetic properties of nanocomposite Nd-Fe-B/ \(\alpha \) -Fe thick-film magnets with Nb additive. Although the deposition rate decreased from approximately 20 to 5 \(\mu \) m/h due to the decrease in the energy from 44 to 11 J, the value of (BH) \(_{\max }\) could be improved by approximately 15 kJ/m \(^{3}\) . The result is considered to be attributed to the reduction in the the numbers and/or size of droplets. Resultantly, we could obtain a 29 \(\mu \) m thick Nd-Fe-B thick-films with the remanence, coercivity, and (BH) \(_{\max }\) values of 0.92 T, 390 kA/m, and 79 kJ/m \(^{3}\) , respectively. [ABSTRACT FROM AUTHOR]

This study proposes a new method to introduce the cementation effect into existing elastoplastic constitutive models for soils. The mechanical properties of cement-treated soil are evaluated via element tests and compared with those of naturally deposited clay. The similarities and differences between cement-treated soils and naturally deposited clays are studied, focusing on two states, the undisturbed and remolded states. The effective stress for cement-treated soils incorporating an internal state variable representing the cementation effect is newly defined to describe the mechanical properties of cement-treated soils. Moreover, by applying this extended effective stress to the super-subloading yield surface (SYS) Cam-clay model, which is an elastoplastic model for soils based on the skeleton structure concept, the scope of this constitutive model is extended to include cement-treated soils. The cementation effect introduced by the proposed method allows reproducing the mechanical behavior of the cement-treated soil. Finally, a brittle behavior not described at the element level can be obtained, leading to a soil–water coupled finite deformation analysis incorporating the proposed constitutive model. [ABSTRACT FROM AUTHOR]

We recently uncovered an association between spinal osteoarthritis and height loss that was independent of incident vertebral fracture. However, the optimal cut-off value of historical height loss (HHL) for discriminating spinal osteoarthritis has not been reported. This cross-sectional study aimed to evaluate the implications of HHL for prevalent vertebral fracture, spinal osteoarthritis, and other co-morbidities in postmenopausal women from the Nagano Cohort Study. In total, 942 Japanese postmenopausal outpatients (mean age: 66.7 years) were investigated. HHL was estimated by arm span – body height difference. Multiple logistic regression analysis revealed significant independent associations of HHL with prevalent vertebral fracture (odds ratio [OR] 1.89; 95% confidence interval [CI] 1.55–2.29), spinal osteoarthritis (OR 1.57; 95% CI 1.31–1.88), and gastroesophageal reflux disease (GERD) (OR 1.75; 95% CI 1.34–2.28) after adjustment for other confounders. Receiver operating characteristic curve analysis of HHL was conducted to discriminate the prevalence of co-morbidities. The optimal cut-off value as defined by the Youden index for prevalent vertebral fracture, spinal osteoarthritis, and GERD was 4.95 cm (area under the curve [AUC] 0.740; 95% CI 0.704–0.776), 2.75 cm (AUC 0.701; 95% CI 0.667–0.735), and 5.35 cm (AUC 0.692; 95% CI 0.629–0.754), respectively. Better understanding of the above relationships and proposed cut-off values will be useful for improving the diagnosis, care management, and quality of life in elderly patients. [ABSTRACT FROM AUTHOR]

Although associations among obesity, adipocytokines, and bone mineral density have been reported, the influence of adipocytokines on osteoporotic fractures remains unclear. This study aimed to assess the impact of the adipocytokines leptin and adiponectin on the risk of incident vertebral and long-bone fractures in postmenopausal women. Clinical data were obtained from the retrospective Nagano Cohort Study of outpatients followed at a single primary care institute in Nagano Prefecture, Japan, between 1993 and 2018. The primary outcome was the occurrence of incident vertebral or long-bone fractures. In total, 1167 Japanese postmenopausal women (mean age: 65.9 years) completed the follow-up and the average observation period was 7.2 years. The subjects were divided into 4 groups (quartile 1 to 4) based respective leptin and adiponectin values. Kaplan–Meier analysis demonstrated a significantly lower incident long-bone fracture rate in the higher quartiles of serum leptin levels (p = 0.002). A significantly higher and more rapid occurrence of incident vertebral fractures, but not long-bone fractures, was found in the highest adiponectin quartile (p < 0.001). A Cox proportional hazards model adjusted for confounders including age, body weight, and either leptin or adiponectin revealed lower leptin levels and higher adiponectin levels as significant independent risk factors for incident long-bone fractures (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.50–0.96; p = 0.03) and vertebral fractures (HR 1.18, 95% CI 1.02–1.37; p = 0.02), respectively. Therefore, serum leptin and adiponectin may be independent risk factors for osteoporotic fractures affecting different bone types and sites. Determining patient adipocytokine levels may help predict the occurrence of specific osteoporotic fractures, thereby enabling optimal treatment for osteoporosis and improving quality of life. • The influence of adipocytokines on osteoporotic fractures remains controversial. • Serum leptin and adiponectin are independent osteoporotic fracture risk factors. • Serum adipocytokine levels may predict the occurrence of osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Congenital radioulnar synostosis (RUS) is a rare skeletal disorder that is characterized by fusion of the radius and ulna. As the etiology of RUS is largely unknown, its treatment options are currently limited. A de novo missense mutation in the zinc finger matrin-type 2 (ZMAT2) gene was newly identified in a 5-year-old boy with RUS using whole-exome sequencing. Herein, we sought to further explore the function of zmat2 in zebrafish. Whole-mount in situ hybridization revealed site-specific expression of zzmat2 in the pectoral fins (equivalent to human upper limbs) and craniofacial regions, while immunohistochemistry showed the expression of zZmat2 in the pectoral fins and heart region. Gene knockdown produced defects in the pectoral fins and dorso-ventral patterning. zzmat2 knockdown also caused embryo dorsalization, a phenotype consistent with reduced/insufficient bone morphogenetic protein (BMP) signaling. These abnormalities were partially rescued by zbmp2b RNA overexpression and fully rescued by simultaneous overexpression of wild-type zzmat2. Importantly, the overexpression of mutant zzmat2 corresponding to the newly-identified mutation did not fully rescue the dorso-ventral patterning defects. The above findings indicate that ZMAT2 regulates skeletal development via the BMP signaling pathway, and its mutation may lead to a loss or reduction in biological activity. Thus, the newly identified ZMAT2 mutation potentially plays a causal role in RUS through deregulation of BMP signaling. • Congenital radioulnar synostosis (RUS) is a rare skeletal disorder of largely unknown etiology. • We identify ZMAT2 as a potential disease-causing gene in a patient with RUS by whole-exome sequencing. • Zebrafish in vivo and ex vivo studies reveal that ZMAT2 can regulate skeletogenesis via BMP signaling. [ABSTRACT FROM AUTHOR]

Presents a study which used laser ablation technique to prepare neodymium-iron-boron thin film magnets with high coercivity. Investigation on the relationship between the magnetic properties and optimum post-annealing technique; Experimental procedure; Results and discussion.

Discusses a study which investigated the room temperature growth of crystalline manganese-zinc ferrite thin films by laser ablation technique. Industrial importance of the preparation of soft ferrite thin films by low temperature processes; Materials and methodology used; Results and conclusions.

Objective Methods Results Conclusion This study aimed to compare the current handgrip strength (HGS) of Kendo athletes with their HGS when they were in university (up to 50 years).Eighty male graduates who were Kendo club members during their university days performed anthropometric and HGS measurements, and these HGS were compared with those measured during their university days (mean age of 19.5 years old).There was no evidence of a statistical difference in HGS between the current measurement and the measurement taken during university [−0.64 (−1.9, 0.67) kg, p = .336]. There was, however, evidence that the difference in HGS depended upon the current age of the individual (t = −6.43, p < .001). When probing the interaction, there were statistical differences between the ages of 24.6 and 38.2 years and between the ages of 47.4 and 69.9 years. Strength increased across time in the younger participants and decreased for those who were older. Between the ages of 38.9 and 46.1 years, there was no evidence of a statistical difference indicating a maintenance of strength.The HGS of Kendo club graduates, which they acquired during their formative years, continued to increase even after they graduated from university and entered their 30s. However, their HGS decreased from age 50, even though they practiced Kendo. [ABSTRACT FROM AUTHOR]

We have already reported some electroplated magnetic films using aqueous solutions. In the present study, we proposed a fabrication process for electroplated soft magnetic films (Ni films) using gel electrolytes. We added gelatin to the plating baths and confirmed that adding 22 g/L of gelatin enabled us to obtain gel electrolytes. Using the gel electrolytes, we electroplated Ni films and evaluated their structural and magnetic properties. From the evaluation of magnetic properties, we confirmed spontaneous magnetization of the Ni films prepared from the gel electrolyte. For obtaining thick Ni films (>1 μm), we investigated stirring the gel electrolyte during plating. As a result, we found that stirring increased the thickness, and our result suggests that stirring the gel electrolyte is useful to increase the deposition rate. In our experimental conditions, the deposition rate of the plating process was ∼0.25 μm/min. From XRD analysis, the structure of Ni films for gel electrolytes was oriented in the fcc (220) plane and slightly different from that for liquid electrolytes. From these results, we found that soft magnetic films could be obtained from the gel electrolyte and that gel plating is one of the attractive fabrication processes of the thick films. [ABSTRACT FROM AUTHOR]

We recently reported the electroplating of Fe-Pt thick films using plating baths with varying concentrations of NaCl, suggesting the potential for coercivity enhancement by Na ions. In the present study, our focus shifted to not Na ions but Cl ones, and we investigated the effect of the Cl ions on the crystal structures and magnetic properties of electroplated Fe-Pt films. With the increasing concentration of Cl ions, the coercivity of the films decreased. Furthermore, XRD analysis suggested that the Cl ions in the plating baths prevent the L10 ordering of the Fe-Pt crystalline phase, leading us to conclude that a Cl-free bath is favorable for preparing Fe-Pt thick-film magnets with high coercivity. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the short- to mid-term clinical results of posterior-stabilized trabecular metal total knee arthroplasty (TKA) with cementless fixation of all components and investigate the radiographic changes of tibial and patellar components and cut bone surfaces over time.Methods: We retrospectively collected the data of 128 knees from 88 consecutive patients who had undergone initial TKA with NexGen LPS-Flex TM implants. A total of 66 knees from 45 patients (mean ± standard deviation age: 70.3 ± 7.5 years) met the selection criteria, which had been employed cementless fixation of all parts and at least 3 years of postoperative follow-up duration. Clinical evaluations included range of motion, conventional knee score, function score, postoperative complications, and revision. For radiological evaluations, the bone contact surface of each implant was divided into 7 zones for tibial component and 2 zones for patellar component. Each region was examined immediately after surgery, at 6 and 12 months, and then every year afterwards.Results: The mean observation period of 45 subjects was 4.2 years. Adequate fixation of tibial components was maintained during follow-up, although the patellar components of 2 knees required revision after repeated falls. No loosening was observed in any implants. The initial gap in tibial components disappeared in all knees, and a reactive line remained in 4 knees. There were no revisions, except for 2 cases, which were ascribed to patellar component fracture caused by repeated falls.Conclusion: Cementless posterior-stabilized trabecular metal TKA appears to be a good surgical option. Longer-term examination for revision cases is required to validate our results. [ABSTRACT FROM AUTHOR]

Presents information on a study which investigated the (110) grain growth and magnetic properties in thin grain-oriented silicon sheets with ultimately low loss. Background on the methods for preparing grain-oriented three percent silicon steel sheets; Experimental procedure; Grain growth and magnetic properties in the final annealing process; Effect of heating rate on magnetic properties in the final annealing process.

Presents information on a study which investigated the magnetic properties of thin three percent textured silicon steel sheet with low loss through two methods. Methodology; Magnetic properties and structure of thin silicon steel sheets annealed in sulfur atmosphere; Magnetic properties and structure of thin silicon steel sheets fabricated by the 2nd method; Conclusions.

Presents information on a study which investigated the effect of film thickness and droplets on magnetic properties in order to improve them. Examination of the surface morphology; Preparation process of a samarium iron nitrogen thin film magnet.

Provides information on a study which obtained Manganese-Zinc ferrite thin films by a low-temperature process using laser-ablation technique. Experimental procedure; Results and discussion; Conclusion.

Emergent properties of 2D materials attract considerable interest in condensed matter physics and materials science due to their distinguished features that are missing in their bulk counterparts. A mainstream in this research field is to broaden the scope of material to expand the horizons of the research area, while developing functional interfaces between different 2D materials is another indispensable research direction. Here, the emergence of electrical conduction at the interface between insulating 2D materials is demonstrated. A new class of van der Waals heterostructures consisting of two sets of insulating transition‐metal dichalcogenides, group‐VI WSe2 and group‐IV TMSe2 (TM = Zr, Hf), is developed via molecular‐beam epitaxy, and it is found that those heterostructures are highly conducting although all the constituent materials are highly insulating. The WSe2/ZrSe2 interface exhibits more conducting behavior than the WSe2/HfSe2 interface, which can be understood by considering the band alignments between constituent materials. Moreover, by increasing Se flux during heterostructure fabrication, the WSe2/ZrSe2 interface becomes more conducting, reaching nearly metallic behavior. Further improvement of the crystalline quality as well as exploring different material combinations are expected to lead to metallic conduction, providing a novel functionality emerging at van der Waals heterostructures. [ABSTRACT FROM AUTHOR]

The aim of this study was to provide definitive reference values for bone mineral density (BMD) and bone turnover markers in the general elderly population. Registered citizens of 50 to 89 years old were targeted for this survey. After random sampling from the resident registry of Obuse town, we established eight groups based on age (50 s, 60 s, 70 s, and 80 s) and gender. A total of 411 people were enrolled. We used a dual-energy x-ray absorptiometry device to measure and evaluate BMD. The bone formation marker bone alkaline phosphatase (BAP) was measured as a bone turnover marker. Bone quality marker pentosidine, and bone resorption markers including urinary total deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), 25-hydroxyvitamin D (25[OH]D), and whole parathyroid hormone (PTH) were also measured as bone turnover markers. Sixty-three people (15.3%) were diagnosed as osteoporosis. BMD decreased with age in the femoral neck and total hip. On the other hand, there was no characteristic change with age in the lumber spine. As for bone markers, pentosidine and DPD increased with aging, although 25(OH)D, whole PTH, and BAP showed no characteristic associations with gender and aging. In terms of the relationship between low BMD and bone markers, there was a significant independent association between low BMD and TRACP-5b in females. In conclusions, hip BMD decreased with aging in men and women. However, there was no characteristic decline with aging in the lumbar spine. All bone markers showed no significant independent characteristics associated with age or gender in a multivariate analysis model, except for a significant association between low BMD and TRACP-5b in females. TRACP-5b was a potentially useful marker for the detection of low BMD. [ABSTRACT FROM AUTHOR]

We examined whether exposure to mild hyperbaric oxygen inhibits the decrease of dopaminergic neurons in the substantia nigra of a neurotoxic animal model with Parkinson’s disease. Mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride and probenecid twice a week were divided into two groups: mice with mild hyperbaric oxygen and those without. The mice with mild hyperbaric oxygen were exposed to 1317 hPa with 45% oxygen for 3 h, three times a week. The decrease in dopaminergic neurons of mice with Parkinson’s disease was inhibited by 11 weeks of exposure to mild hyperbaric oxygen. We conclude that exposure to mild hyperbaric oxygen is effective in preventing the progression of Parkinson’s disease. [ABSTRACT FROM AUTHOR]

We have prepared Fe-Ni-system bilayer ribbons with different magnetostriction (compositions) and investigated the improvement of soft magnetic properties using the magnetoelastic effect. A toroidal core with D = 10 mm was made from the Fe6Ni94/Fe56Ni44 bilayer ribbon, and the B-H loop of the core was measured. The shape of the hysteresis loop dramatically changed depending on the inner layer (inner magnetic phase). This result indicates that the direction of the anisotropy induced by bending stress was changed depending on the inner layer. The slope of the B-H loop and coercivity reduced when the Fe56Ni44 layer was on the inner side. From the experimental results, we found that domain rotation was dominant for the magnetization process. Consequently, the increase in the coercivity over frequency could be suppressed by controlling the magnetization process. From these results, we found that a thin bilayer ribbon with positive and negative magnetostriction constant is an attractive material for reducing iron losses under high frequency. [ABSTRACT FROM AUTHOR]

We have previously proposed a simulation method of an initial flux loss in permanent magnets using finite element method, and confirmed that predicted flux loss of an Nd-Fe-B boned ring magnet showed good agreement with measured flux loss. In this paper, we applied our proposed method to an Nd-Fe-B boned ring magnet in an SPM motor. We modeled a rotor composed of an Nd-Fe-B bonded ring magnet and a soft magnetic core made from silicon steels, and carried out the simulations for magnetizing process and prediction process of the flux loss. From the simulation results, we found that the inner side of the ring magnet has large flux loss. In order to reduce in flux loss, we enhanced the coercivity in the inner side of the ring magnet by partial replacement with another bonded magnet with high coercivity. Consequently, we found that the ring magnet with locally enhanced coercivity is effective to reduce in the flux loss. [ABSTRACT FROM AUTHOR]

This paper proposes a combined-loading elastoplastic constitutive model (CL model) for a unified description of the mechanical behavior of soil materials, including clay, sand, and intermediate soil. This mathematical model combines the super-subloading yield surface Cam-clay model and the non-associated Drucker–Prager (DP) model. The first model introduces the skeleton soil structure concept into the Cam-clay model based on critical-state soil mechanics. It describes the mechanical behavior of naturally deposited clay more accurately than the existing model does. The non-associated DP model considers the frictional properties of granular materials and is widely used to describe the undrained shear behavior, particularly that of sandy soil. The newly proposed model is one in which these two independently existing models simultaneously or independently work in loading states according to the loading criterion, which can be derived as a natural result from plastic multipliers. This framework allows for a unified description of a wide range of soil materials, including naturally deposited clayey soils and sandy soils. [ABSTRACT FROM AUTHOR]

Abstract: Subcooled flow boiling of water was tested for a large heating surface of 5cm length and 2cm width in a horizontal rectangular channel of 5mm height and 24mm width. Microbubble emission boiling occurred in transition boiling at 40K of liquid subcooling and 0.5m/s of liquid velocity and the maximum heat flux was higher than the ordinary critical heat flux. Maximum heat flux obtained was 5MW/m2. In subcooled pool boiling of alcohol–water mixtures, critical heat fluxes were higher than that of water, especially, polyhydric alcohol–water mixtures such as 1-butanol and 2-propanol showed about 50% higher critical heat fluxes than water. In the subcooled flow boiling with small heating surface of 10mm×10mm, microbubble emission boiling occurred in transition boiling and the maximum heat fluxes were 10% higher than the water. [Copyright &y& Elsevier]

This paper describes a new loading cam that always applies the optimum loading force to the variator used in a toroidal continuously variable transmission (CVT). The hysteresis of the loading force is shown to be caused by the spinning loss of the cylindrical cam roller of the conventional loading cam. This hysteresis is greatly reduced in the new loading cam by using a tapered cam roller that is free of spinning loss. Reducing the hysteresis lowers the average loading force, enabling the new loading cam to improve the torque capacity of a CYT. [Copyright &y& Elsevier]

Previous studies have shown decreased bone mineral density (BMD) due to an unknown mechanism in Ehlers-Danlos Syndrome (EDS) patients and described approaches to treatment for osteoporosis in EDS. To date, however, there is no established method of treatment. In this study, we investigated two patients with EDS to clarify the efficacy and safety of denosumab treatment in EDS patients with osteoporosis. We retrospectively enrolled two EDS patients with osteoporosis who underwent denosumab therapy. Patient 1 was a 59-year-old male with classical EDS and osteoporosis who received a 48-month course of denosumab therapy. His lumbar BMD and total hip BMD were 1.335 g/cm2 and 0.762 g/cm2 before treatment, respectively. Forty-eight months later, the lumbar and total hip BMD showed gains of 1.6% and 11.4%, respectively. Patient 2 was a 42-year-old male with vascular EDS and osteoporosis who received an 18-month course of denosumab therapy. His lumbar BMD and total hip BMD were 0.763 g/cm2 and 0.583 g/cm2 before treatment, respectively. Eighteen months later, the lumbar and total hip BMD showed gains of 5.0% and 1.8%, respectively. No fractures or other complications were recorded during the observational period in both cases. This is the first experience of denosmab therapy on patients with EDS and osteoporosis. Denosumab, administered safely with no serious adverse effects such as fractures, exerted a fluctuating but probably positive effect regarding BMD and could be a treatment option on these patients. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective observational study from the Nagano Cohort Study.Objective: Clarify the association between spinal osteoarthritis and loss of stature in postmenopausal women.Summary Of Background Data: Loss of stature with aging is known to deteriorate health-related quality of life and has been implicated with increased mortality. Although the association of vertebral fracture with height loss has been well documented, the relationship between stature loss and spinal osteoarthritis remains unclear.Methods: We retrospectively investigated Japanese postmenopausal women recruited from the Nagano Cohort Study. The participants were outpatients at a primary care institute in Nagano prefecture, Japan. A total of 977 postmenopausal patients (mean age: 65.8 yr) completed a minimum of 1 year of follow-up, with an average observation period of 7.6 years. Quartile analysis on the prevalence of spinal osteoarthritis and occurrence of incident fracture was performed based on the rate of stature change per year (Δ cm/yr). Multiple regression analysis was also conducted to identify the determinants of stature change.Results: The lower quartiles of stature change rate (i.e., more rapid stature loss) displayed a significantly higher prevalence of spinal osteoarthritis (P < 0.001) and incident vertebral fracture (P < 0.001). A statistically significant independent negative association for spinal osteoarthritis prevalence with change in stature was revealed by multiple regression analysis after adjusting for confounders including incident vertebral fracture. The partial regression coefficient for spinal osteoarthritis was -0.18 (95% confidence interval -0.33 to -0.03; P = 0.016).Conclusion: This study demonstrated an independent association of spinal osteoarthritis with stature loss in postmenopausal women. Adequate understanding of this relationship and appropriate treatment approaches will help improve health-related quality of life in elderly patients.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Abstract: Anisotropic 270--thick composite-bonded magnets using the spherical fine powder together with HDDR- can be obtained, and the value of reached , which is extremely higher than that of conventional isotropic -bonded magnets. It was also confirmed that the thermal stability for the thin composite magnets was good. [Copyright &y& Elsevier]

The method of enhancing coercivity of isotropic Nd-Fe-B flakes using simultaneous diffusion of Dy and crystallization from the amorphous state was also applied to Nd-Fe-B powders, in this study. Metal Dy coating was synthesized on amorphous Nd2.36Fe14B1.05 powders by the vapor deposition method, and the powders were crystallized by a flash annealing. Simultaneous diffusion of Dy from their surfaces using the crystallization enhanced the coercivity of isotropic Nd-Fe-B powders. The coercivity Hc increased and the remanence Mr decreased nearly linearly with the amount of Dy, and the coating of 4.5 wt.% Dy resulted in 25.3% increase in Hc and 6.5% decrease in Mr. The decrease in Mr of the Nd-Fe-B powders is nearly the same in magnitude to that previously reported for Nd2.36Fe14B1.05 flakes, which suggests that the method of Dy diffusion using crystallization from amorphous state is applicable to Nd-Fe-B amorphous powders as well as flakes. The energy-dispersive X-ray spectroscopy revealed that Dy coating is inhomogeneous, and a further enhancement in Hc is expected by improving the coating method. [ABSTRACT FROM AUTHOR]

We prepared L10 ordered Fe50Pt50 thick-films on Cu substrates using the electroplating method and evaluated their high-temperature properties in the temperature range of 25-200°C. The Hc and the (BH)max at 150°C for the Fe50Pt50 films annealed by ordinary annealing method (700°C, 60 min) were 500 kA/m and 50 kJ/m3, respectively, and the thermal coefficient of Hc was -0.3%/°C. To improve the high-temperature properties, we employed a flash annealing method using an infrared furnace (8 kW). The flash annealing method improved the high-temperature properties (Hc = 700 kA/m, (BH)max = 70 kJ/m3 at 150°C) and the thermal coefficient (-0.21%/°C). The thermal stability of the films is comparable to those for Sm-Co-system magnets and better than for Nd-Fe-B-system ones. We, therefore, found the L10 ordered Fe50Pt50 films prepared by the electroplating and the flash annealing are one of the hopeful small magnets in the wide temperature range. [ABSTRACT FROM AUTHOR]

We prepared Fe-Ni thick-films (> 1 μm) using an electroless deposition method and evaluated the magnetic properties and the crystal structures. The deposition rate depended on the concentration of dimethylamine-borane (DMAB), which is a reducing agent used in the present study, and we obtained a high deposition rate (> 10 μm/h) for Fe30Ni70 films when the DMAB concentration is higher than 3 g/L. From structural analyses of the films, we found that the films have very fine fcc Fe-Ni crystals in the amorphous magnetic phase. From the investigation of Co additives for the improvement in the surface conditions, we confirmed that a small amount of Co effectively works to obtain the smooth surfaces. As a result, we could obtain the Fe-Ni-system thick-films with low coercivity (50 A/m) and smooth surfaces. [ABSTRACT FROM AUTHOR]

Many types of cancer cells show a characteristic increase in glycolysis, which is called the "Warburg effect." By screening plant extracts, we identified one that decreases cellular adenosine triphosphate (ATP) levels and suppresses proliferation of malignant melanoma B16F10 cells, but not of noncancerous MEF cells. We showed that its active ingredient is emodin, which showed strong antiproliferative effects on B16F10 cells both in vitro and in vivo. Moreover, we also found that emodin can function as a mitochondrial uncoupler. Consistently, three known mitochondrial uncouplers also displayed potent antiproliferative effects and preferential cellular ATP reduction in B16F10 cells, but not in MEF cells. These uncouplers provoked comparable mitochondrial uncoupling in both cell types, but they manifested dramatically different cellular effects. Namely in MEF cells, these uncouplers induced three to fivefold increases in glycolysis from the basal state, and this compensatory activation appeared to be responsible for the maintenance of cellular ATP levels. In contrast, B16F10 cells treated with the uncouplers showed less than a twofold enhancement of glycolysis, which was not sufficient to compensate for the decrease of ATP production. Together, these results raise the possibility that uncouplers could be effective therapeutic agents specifically for cancer cells with prominent "Warburg effect." [ABSTRACT FROM AUTHOR]