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IF1 is a natural inhibitor protein for mitochondrial FoF1 ATP synthase that blocks catalysis and rotation of the F1 by deeply inserting its N-terminal helices into F1. A unique feature of IF1 is condition-dependent inhibition; although IF1 inhibits ATP hydrolysis by F1, IF1 inhibition is relieved under ATP synthesis conditions. To elucidate this condition-dependent inhibition mechanism, we have performed single-molecule manipulation experiments on IF1-inhibited bovine mitochondrial F1 (bMF1). The results show that IF1-inhibited F1 is efficiently activated only when F1 is rotated in the clockwise (ATP synthesis) direction, but not in the counterclockwise direction. The observed rotational-direction-dependent activation explains the condition-dependent mechanism of IF1 inhibition. Investigation of mutant IF1 with N-terminal truncations shows that the interaction with the γ subunit at the N-terminal regions is crucial for rotational-direction-dependent ejection, and the middle long helix is responsible for the inhibition of F1.

In the countries like Japan where anticoagulation is not recommended in hemodialysis patients, the feasibility of percutaneous left atrial appendage closure (LAAC) in hemodialysis patients with non-valvular atrial fibrillation (NVAF) accompanying high risks of thromboembolic stroke and bleeding remains unknown. Peri-procedural and 45-day clinical outcomes following LAAC using WATCHMAN system, which were performed in our institute between Jun 2020 and April 2022 according to the Japanese Circulation Society guidelines, were retrospectively compared between those with and without hemodialysis. 118 patients (median 79 years, 81 men) consisting of 25 hemodialysis patients and 93 non-hemodialysis patients were included. CHADS score was 3 (2, 4) in the hemodialysis patients and 3 (2, 4) in the non-hemodialysis patients (p = 0.98). HAS-BREAD score was 4 (3, 5) in the hemodialysis patients and 3 (2, 3) in the non-hemodialysis patients (p

Atherosclerosis is a risk factor for both aortic stenosis (AS) and coronary artery disease. This study aimed to investigate whether anti-atherosclerotic therapy (AT), defined as the simultaneous use of antiplatelet agents, statins, and renin aldosterone system inhibitors, had long-term clinical benefits for patients who underwent transcatheter aortic valve replacement (TAVR). Between October 2013 and May 2017, 2518 patients (31% men; median age, 85 years) who underwent TAVR in 14 Japanese centers were divided into two groups: patients who were prescribed anti-atherosclerotic therapy (AT, n = 567) and patients who were not (no AT, n = 1951). The median follow-up period for this cohort was 693 days (interquartile range, 389-870 days). Compared to no AT group, AT group was associated with significantly lower 2-year all-cause mortality (11.7% vs. 16.5%; log-rank p = 0.002) and 2-year cardiovascular mortality rates (3.5% vs. 6.0%; log-rank p = 0.017). In a propensity-matched cohort (n = 495 each; median follow-up, 710 days [IQR, 394 - 896 days]), patients in AT group had a lower prevalence of 2-year cardiovascular mortality (3.8% vs. 6.2%, log-rank p = 0.024) than that in the no AT group. In the multivariate stepwise regression analysis, AT was a significant predictor of cardiovascular mortality (hazard ratio 0.45; 95% confidence interval 0.25-0.80; p = 0.007). AT may improve survival in post-TAVR patients. Future studies are necessary to identify an optimal treatment regimen to improve long-term outcomes after TAVR.

Elevated serum angiopoietin-2 levels in patients with acute myocardial infarction-related cardiogenic shock with and without intra-aortic balloon pump as well as acute decompensated heart failure are associated with short-term mortality. However, its prognostic impact in patients with cardiogenic shock supported by Impella-incorporated mechanical circulatory support (MCS) remains unknown. Patients who received temporary MCS (Impella alone or Impella and veno-arterial extracorporeal membrane oxygenation) in our institute between August 2018 and January 2022 were included in this prospective study. The serum levels of angiopoietin-2 were measured just before and following the initiation of temporary MCS therapy. Association between the levels of serum angiopoietin-2 and 30-day mortality was investigated. A total of 38 patients (median 72 years old, 63% men) were included. The median levels of serum angiopoetin-2 tended to decrease from baseline to 4 days following the initiation of temporary MCS from 5.2 (3.3, 10.5) ng/mL to 4.8 (2.7, 6.8) ng/mL (p = 0.132). A higher angiopoietin-2 ( 6.8 ng/mL) following the initiation of temporary MCS was associated with higher 30-day mortality (89.7% versus 44.4%, p = 0.0048) with an odds ratio 18.946 (95% confidence interval 1.624-218.695, p = 0.018) adjusted for potential confounders. A higher serum angiopoietin-2 level following the initiation of Impella-incorporated temporary MCS, instead of baseline angiopoetin-2 level, was associated with higher short-term mortality.

No data are available on extended dual anti-platelet therapy (DAPT) duration which may influence long-term prognosis (later than 1 year) after transcatheter aortic valve replacement (TAVR). Therefore, this study is aimed to evaluate whether discontinuing DAPT within 1 year had an impact on adverse events after TAVR. Using data from the OCEAN-TAVI registry, we assessed 1008 patients who survived the first year after TAVR with DAPT since discharge. Patients were divided into ‘DAPT group’ (n = 462), comprising patients who took DAPT at both discharge and 1 year, and ‘stop-DAPT group’ (n = 546), comprising patients who took DAPT at discharge and single anti-platelet therapy (SAPT) at 1 year. We compared the incidence of cardiovascular (CV) death, major and minor bleeding, and ischemic stroke later than 1 year after TAVR between the two groups. A total of 28 CV deaths were observed later than 1 year after TAVR. The stop-DAPT group had a significantly lower incidence of CV death than the DAPT group (1.8% vs. 4.9%, log-rank P = 0.029). Stop DAPT was associated with lower CV death later than 1 year of TAVR in Cox regression analysis (adjusted hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.20–0.99), and in analysis with inverse probability of treatment weighting method using propensity score (adjusted HR, 0.45; 95% CI, 0.20–0.98). Our study demonstrated that switching from DAPT to SAPT within 1 year of TAVR was significantly associated with a lower CV death later than 1 year after TAVR.

Higher B-type natriuretic peptide (BNP) levels at discharge predict higher cardiovascular events in transcatheter aortic valve implantation (TAVI) patients. However, it is not known whether the reduction in BNP levels effectively predicts prognosis. The purpose was to examine the predictive power of percentage changes in BNP levels for all-cause death and hospitalization of heart failure (HF) after TAVI in severe aortic stenosis (AS) patients. We analyzed 70 severe AS patients treated with TAVI who had a record of BNP > 200 pg/mL. Receiver operating characteristics (ROC) curves analysis for all-cause death and hospitalization for HF after TAVI revealed the cut-off percentage change in BNP, and we divided the study population into the “responder group” and the “non-responder group”. The cut-off level for the percentage change in BNP evaluated by ROC analysis was a 40% decrease in BNP (AUC = 0.733, p

Homogeneous and accurate hypocenter distribution along the Japan Trench is important to better understand the process of plate subduction and the occurrence mode of large earthquakes. The seafloor seismic network (S-net) deployed recently along the Japan Trench has revealed new seismic activity including shallow slow earthquakes. However, conventional microseismic observations, such as those reported in the Japan Meteorological Agency (JMA) unified earthquake catalog, have been limited to land-based stations. Thus, steady seismic activity occurring at the shallow plate boundary, which is far from land is not always recorded. In the present study, we construct an automatic earthquake catalog using the nationwide observation network, including S-net. Because false detections caused by noise account for about 5% of automatically determined hypocenters, we attempted to reduce false detections using ensemble learning methods such as random forest and AdaBoost. First, we created a training dataset of earthquakes and noise by visual inspection based on the data recorded in the automatically determined catalog over a 2-month period, and we trained the dataset using the hypocenter and phase data as input. As a result of the training, AdaBoost was able to reduce the noise to about one-fifth of the total false detections, which is equivalent to 1%, while keeping the number of hypocenters above 99%. This method will contribute to significantly improving the efficiency of seismic activity monitoring and cataloging. In addition, the automatic denoised catalog data revealed that from January to August 2020, the completeness magnitude wasM1.6 along the Japan Trench. These microearthquakes were concentrated at depths of 20–50 km around the upper surface of the subducting Pacific Plate and are complementary to the slow earthquakes occurring at 10–20-km depths. Exceptionally, microearthquakes were observed off Iwate and Ibaraki prefectures, which correspond in location to areas of clustered foreshock activity. This spatial heterogeneity in microseismic activity is similar to the spatial complementary between the coseismic slip and afterslip of the 2011 Tohoku earthquake, which may be related to differences in interplate frictional properties and stress changes in the surrounding crust.

Mice are the most commonly used laboratory animals for studying diseases, behaviour, and pharmacology. Behavioural experiment battery aids in evaluating abnormal behaviour in mice. During behavioural experiments, mice frequently experience human contact. However, the effects of repeated handling on mice behaviour remains unclear. To minimise mice stress, methods of moving mice using transparent tunnels or cups have been recommended but are impractical in behavioural tests. To investigate these effects, we used a behavioural test battery to assess differences between mice accustomed to the experimenter’s handling versus control mice. Repeatedly handled mice gained slightly more weight than control mice. In behavioural tests, repeatedly handled mice showed improved spatial cognition in the Y-maze test and reduced anxiety-like behaviour in the elevated plus-maze test. However, there was no change in anxiety-like behaviour in the light/dark transition test or open-field test. Grip strength, rotarod, sociability, tail suspension, Porsolt forced swim, and passive avoidance tests revealed no significant differences between repeatedly handled and control mice. Our findings demonstrated that mice repeatedly handled by the experimenter before behavioural tests showed reduced anxiety about high altitudes and improved spatial cognition, suggesting that repeated contact can affect the results of some behavioural tests.

The midterm safety and feasibility of transcatheter aortic valve implantation (TAVI) for patients with a history of coronary artery bypass graft (CABG) and high operative risk are unclear. This study compared the midterm outcomes of patients undergoing TAVI with or without previous CABG surgery. Between October 2013 and July 2016, 1,613 patients underwent TAVI according to the Optimized CathEter vAlvular iNtervention (OCEAN)-TAVI registry (previous CABG: n = 120; no previous CABG: n = 1493). The propensity score comprised the variables of the Society of Thoracic Surgeons Score, previous myocardial infarction, peripheral artery disease, chronic kidney disease > stage 2 (estimated glomerular filtration rate

Rotary ATPases are unique rotary molecular motors that function as energy conversion machines. Among all known rotary ATPases, F1-ATPase is the best characterized rotary molecular motor. There are many high-resolution crystal structures and the rotation dynamics have been investigated in detail by extensive single-molecule studies. In contrast, knowledge on the structure and rotation dynamics of V1-ATPase, another rotary ATPase, has been limited. However, recent high-resolution structural studies and single-molecule studies on V1-ATPase have provided new insights on how the catalytic sites in this molecular motor change its conformation during rotation driven by ATP hydrolysis. In this review, we summarize recent information on the structural features and rotary dynamics of V1-ATPase revealed from structural and single-molecule approaches and discuss the possible chemomechanical coupling scheme of V1-ATPase with a focus on differences between rotary molecular motors.

EhV-ATPase is an ATP-driven Na+ pump in the eubacteria Enterococcus hirae (Eh). Here, we present the first entire structure of detergent-solubilized EhV-ATPase by single-particle cryo-electron microscopy (cryo-EM) using Zernike phase plate. The cryo-EM map dominantly showed one of three catalytic conformations in this rotary enzyme. To further stabilize the originally heterogeneous structure caused by the ATP hydrolysis states of the V1-ATPases, a peptide epitope tag system was adopted, in which the inserted peptide epitope sequence interfered with rotation of the central rotor by binding the Fab. As a result, the map unexpectedly showed another catalytic conformation of EhV-ATPase. Interestingly, these two conformations identified with and without Fab conversely coincided with those of the minor state 2 and the major state 1 of Thermus thermophilus V/A-ATPase, respectively. The most prominent feature in EhV-ATPase was the off-axis rotor, where the cytoplasmic V1 domain was connected to the transmembrane Vo domain through the off-axis central rotor. Furthermore, compared to the structure of ATP synthases, the larger size of the interface between the transmembrane a-subunit and c-ring of EhV-ATPase would be more advantageous for active ion pumping.

Background Many neuropsychiatric disorders develop in early life. Although the mechanisms involved have not been elucidated, it is possible that functional abnormalities of parvalbumin-positive interneurons (PV neurons) are present. Several previous studies have shown that juvenile stress is implicated in the development of neuropsychiatric disorders. We aimed to clarify the effects of juvenile stress on behavior and on the central nervous system. We investigated behavioral abnormalities of chronically-stressed mice during juvenilehood and the effect of juvenile stress on PV neurons and WFA-positive perineuronal nets (PNNs), which are associated with vulnerability and plasticity in the mouse brain. Results Due to juvenile stress, mice showed neurodevelopmental disorder-like behavior. Juvenile stressed mice did not show depressive-like behaviors, but on the contrary, they showed increased activity and decreased anxiety-like behavior. In the central nervous system of juvenile stressed mice, the fluorescence intensity of WFA-positive PNNs decreased, which may signify increased vulnerability. Conclusion This study suggested that juvenile stressed mice showed behavioral abnormalities, resembling those seen in neuropsychiatric disorders, and increased brain vulnerability.

Duloxetine is an effective therapeutic agent for chemotherapy-induced peripheral neuropathy (CIPN). However, predictors of duloxetine response have not been adequately explored. Therefore, this retrospective study was performed to identify predictive factors of duloxetine response in CIPN patients to guide future strategies to improve the quality of life of patients undergoing chemotherapy. The participants were 74 cancer patients who were given duloxetine for relief of CIPN at our institute between October 2010 and January 2016. Variables were extracted from clinical records for regression analysis of factors related to relief of CIPN. We evaluated the effect of duloxetine 2 weeks after administration. Groups were categorized according to degree of improvement: poor, effective, and very effective. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the usefulness of duloxetine. Threshold measures were examined using a receiver operating characteristic analysis (ROC) curve. Body height [odds ratio (OR) 0.943, 95% confidence interval (CI) 0.889-0.997; P = 0.0387], history of docetaxel use (OR 0.084, 95% Cl 0.009-0.814; P = 0.0325), and site of symptom (upper limb) (OR 3.848, 95% Cl 1.072-13.807; P = 0.0387) were significant factors related to the effect of duloxetine. ROC curve analysis of the poor effect group indicated a threshold for body height of >171.4 cm (area under the curve [AUC] = 0.61). In conclusion, body height (low), history of docetaxel use (less), and site of symptom (upper limb) were shown to be predictive factors for the usefulness of duloxetine for CIPN in patients undergoing chemotherapy.

The rapid determination of its magnitude soon after a great earthquake is necessary for the issuing of effective tsunami warnings, as demonstrated in the great earthquake off Tohoku district in Japan on March 11, 2011. The earthquake magnitude for the first tsunami warning was underestimated due to magnitude saturation. This paper proposes a method to determine magnitude rapidly from peak velocity and displacement of long-period seismic waves up to 100 seconds at local stations. When waveform data at local stations are available, the magnitude from S-wave peaks is expected to be determined faster than that from only P-wave peaks. It takes about 140 seconds to estimate a magnitude of about 9 for the March 11, 2011, earthquake, which would enable us to issue the first tsunami warning within three minutes after the same type of earthquake.

Present study aimed to investigate the impact of anti-inflammatory cytokines provoked by the hemoglobin scavenger receptor, CD163, on left ventricular (LV) functional recovery after successful reperfusion in patients with acute myocardial infarction (AMI). Intraplaque hemorrhage accelerates plaque destabilization. Extracellular hemoglobin is cleared by CD163, a macrophage scavenger receptor. This process provokes secretion of anti-inflammatory atheroprotective cytokine, interleukin (IL)-10. In 40 patients with the first AMI, coronary atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI), stained with antibodies to CD163 and IL-10. LV function was determined by echocardiography before PCI and 6 months after PCI. %CD163 was defined as ratio of CD163 (+)-cells to whole cells. %IL-10 was expressed as the ratio of positively stained areas per total tissue. Patients were divided into two groups depending on the amount of CD163 (+)-cells: CD163 > 10 % (CD163high, n = 20) and CD163 ≤ 10 % (CD163low, n = 20). CD163high group had significantly higher %IL-10. Final thrombolysis in myocardial infarction (TIMI) flow grade was significantly lower in CD163high group. In subgroups with the final TIMI-3 flow (CD163high-Reflow, n = 15 and CD163low-Reflow, n = 20), the time to reperfusion, infarct size, LV dimensions and fractional shortening (%FS) before PCI were similar. Significant correlation was observed between %IL10 and changes in LV dimensions (diastole, r = −0.49, P = 0.01; systole, r = −0.65, P < 0.01) or %FS (r = 0.51, P < 0.01) at 6 months after PCI. Plaque with CD163(+)-macrophages could impair distal flow after primary PCI. However, CD163(+)-macrophages enhance the anti-inflammatory cytokine expression that aids in ventricular functional recovery if distal flow can be achieved by successful reperfusion.

In this study, we analyzed the photoelectric current generated by bacteriorhodopsin adsorbed on a polymer film, "Lumirror" (Muneyuki et al. in FEBS Lett 427:109-114, 1998). We could examine the photoelectric current over a wide range of light intensity and pH values using the same membrane owing to the mechanical and chemical stability of the thin polymer film. We analyzed the photoelectric current by comparison with a simple equivalent electric circuit. Analysis of experimental results obtained at different light intensities suggested that the electromotive force of the bacteriorhodopsin was independent of light intensity. The pH dependence of the photoelectric current suggested that the bacteriorhodopsin could generate a maximum electromotive force at approximately pH 6.

A lithium-encapsulated fullerenol Li@C60(OH)18, as an example of a polar solvent-soluble endohedral fullerene derivative, has been synthesized and fully characterized by infrared spectroscopy, nuclear magnetic resonance spectroscopy, UV spectroscopy, electron spin resonance (ESR) spectroscopy, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), elemental analysis, thermogravimetric analysis, and inductively coupled plasma-atomic emission spectroscopy (ICP-AES), and the particle size was determined using the induced grating (IG) method, and scanning probe microscopy. The encapsulated Li+ was clearly detected by 7Li NMR at very high field in the range −15 to −19 ppm, an intermediate lithium-encapsulated fullerenol was detected by MALDI-TOF-MS, and the molar ratio of lithium-encapsulated fullerenol to empty fullerenol was quantitatively determined to be 12:88 by ICP-AES. The solid-state ESR and particle size measurements using the IG method showed the characteristic anionic behavior with no external counter cations, in what can be called a “cation-encapsulated anion nanoparticle”, revealing the drastic differences between its properties and those of empty C60(OH)16. Open image in new window

Lactoferrin (Lf) can solubilize more than a 70-fold molar equivalent of iron in the presence of bicarbonate anions. The resulting iron–Lf complex (FeLf) is a useful food ingredient for iron fortification to prevent anemia. Although FeLf has greater thermal stability than Lf, a pasteurizing technique for FeLf has not been established. The aim of the present study was to develop a practical technique to pasteurize FeLf based on its thermal stability with the aid of a polysaccharide. FeLf [0.1 %, weight/weight (w/w) ratio] was heated at 80 °C for 3 min under various pH (5.5–8.0) and electrical conductivity (0.1–6.0 mS/cm) levels. Overall, FeLf was thermally stable and was hardly affected by pH or electrical conductivity, although aggregation and precipitation occurred when FeLf was heated at pH 6.0–7.5 in the presence of salt and electrical conductivity >3.0 mS/cm. When 0.01 %–0.4 % (w/w) of soluble soybean polysaccharide (SSPS) was added to 0.01 % (w/w) FeLf solution, the FeLf remained soluble and maintained its iron-holding property at pH 6.5, even when heated at 120 °C for 4 min. Particle charge measurements showed that the ζ-potential of FeLf-SSPS became negatively charged following the addition of SSPS, which was associated with the improved thermal stability of FeLf. These results have important implications for the use of FeLf in developing liquid-based food products.

International audience; Lactoferrin (Lf) can solubilize more than a 70-fold molar equivalent of iron in the presence of bicarbonate anions. Iron solubilized by Lf (FeLf) is a useful food product for iron fortification, preventing anaemia with no risk of toxicity. However, the mechanism underlying this iron solubilization is not yet well understood. The objective of this study was to investigate the effects of thermal treatments on the iron-solubilizing capacity of Lf in the presence of sodium bicarbonate. Lf was subjected to thermal treatment at 50-80 A degrees C for 10 min, and the Lf heated to over 70 A degrees C was precipitated by the addition of Fe(III). No precipitation was observed in FeLf-like mixtures of heated Lf when various other cations were substituted for Fe(III): Cu(II), Zn(II), Mg or Na. The precipitation was related to the degree of thermal denaturation of Lf, accompanied by the formation of high-molecular-weight aggregates as disulphide bonds were established. Transferrin, alpha-lactalbumin and beta-lactoglobulin did not solubilize Fe(III), suggesting that the Fe(III)-solubilizing capacity is characteristic of Lf. In conclusion, native Lf is responsible for iron solubilization in the presence of bicarbonate anions. Owing to the application of native Lf to the manufacture of FeLf, FeLf can improve specific food products by supplementing their iron content.

A conventional SUS 316L low carbon stainless steel has been processed by Equal channel angular pressing (ECAP) to the equivalent shear strain equal to 2, 4, 6 or 8 at different temperatures ranging from 250 °C to room temperature. The aim of this study is to gain extra control over the “strength-ductility” combination via nanostructure formation, involving twinning and/or strain-induced phase transformation. The resultant microstructure is examined by transmission electron microscopy, X-ray diffraction and electron back scattered diffraction (EBSD) techniques. Substantial structure refinement down to nanoscale is observed in parallel with significant enhancement of tensile yield and ultimate tensile stress, both exceeding 1GPa. A considerable resistance to fracture during localized plastic flow and a fairly good elongation to fracture in tension is reported.

We have previously reported the early uptake and transport of foreign particles into Peyer's patches (PPs) of newborn and 2-month-old calves and shown that the peak uptake of particles occurs 6 h after inoculation, in addition to site- and size-related effects on particle uptake. We now report the distribution of immune cells within PPs of the distal ileum in newborn and 2-month-old calves inoculated with carbon black. The types of immune cells involved in the early uptake and transport of recombinant mouse prion protein (rMPrP) within PPs of newborn calf were investigated by using monoclonal antibodies CD11c, CD14, CD68, CD172a, and CD21. CD11c(+), CD14(+), CD68(+), CD172a(+), and CD21(+) immune cells were widely distributed in four tissue compartments (villi, dome, interfollicular region, and follicles) of PPs in the distal ileum of newborn and 2-month-old calves, whereas CD11c(+), CD14(+), CD172a(+), and CD21(+) immune cells were more prominently distributed in the dome areas of newborn calves than in 2-month-old calves. Moreover, CD11c(+) and CD14(+) dendritic cells, CD172a(+) and CD68(+) macrophages, and CD21(+) follicular dendritic cells containing rMPrP were primarily observed in the dome and inner follicular regions. The deposition of rMPrP within CD11c(+), CD14(+), CD172a(+), and CD68(+) cells, but not CD21(+) cells, was detected in villous regions. rMPrP-positive immune cells within the interfollicular regions included only CD11c(+) and CD172(+) cells. Although the particles used in this investigation do not include the infectious prion protein, PrP(Sc), our experimental setup provides a useful model for studying immune cells involved in the early uptake and transport of PrP(Sc).

A new lighting panel consists of the light tube that shifts a point light source (light emitting diode) to line light source, and the light guide plate that shifts light from the light tube to surface illuminant. The light tube has length of 27.5 mm and has thickness of 1.0 mm, and width has the light incidence part of 2.6 mm, and it narrows toward the tip. On one side of the light tube, there are a lot of very small prisms that reflect light to the other side. The dimensions of the light guide plate are 30.0 mm × 30.0 mm × 1.0 mm and the reflection dots are arranged in a range of 27.0 mm × 27.0 mm. The bottom surface of the light guide plate is fitted with numerous truncated-cone-shaped reflection dots, and the light that comes out from the light tube reflects in them and comes out of the upper part of the light guide plate. We designed, fabricated, and evaluated the lighting panel by using LIGA process and UV-LIGA process.

To examine the correlation between airborne ethylene glycol dimethyl ether (EGdiME) exposures and the urinary methoxyacetic acid (MAA) and to approach the issue of a permissible exposure limit for EGdiME.The survey was conducted on Thursday. Workers occupationally exposed to EGdiME, as well as nonexposed controls, were studied in combination with one of the authors, who was coincidentally exposed to EGdiME while carrying out the study. Air levels of EGdiME were determined by personal sampling on passive gas tubes. Urine was collected from nine control subjects and ten workers immediately before and after the shift, and from one of the authors at intervals during 12 h. The analyses of EGdiME in air and MAA in urine were performed by gas chromatography with flame ionization detection.The time-weighted average (TWA) air levels of EGdiME ranged from 0.7 to 10.5 ppm during 8 h work shifts. The urinary levels of MAA in one of the authors increased continuously during exposure and after the end of exposure. The levels of urinary MAA in the exposed workers were significantly higher than those in the control subjects. On the other hand, the postshift values were higher than the preshift values in the exposed workers, but the difference was not significant. A linear correlation was found between the TWA air levels of EGdiME and creatinine-adjusted MAA levels in urine collected at the end of the shift (r = 0.933; P0.0001). According to our equation, a linear extrapolation to the biological limit value recommended by Shih et al. (1999) of 40 mg MAA/g crea indicated an average inhalation exposure to EGdiME over the workweek of 12 ppm.These results indicate that the determination of MAA in urine is suitable for use in the biological monitoring of EGdiME exposure.

Cyclosporine A (CsA) is known to have testicular toxicity, leading to male infertility. The occurrence of numerous anomalous spermatids and residual bodies in the epididymal ducts of rats treated with CsA was observed in our previous studies. To examine the fine structural changes of impaired spermiogenesis induced by CsA, rats were treated s.c. with 40 mg/kg/day CsA for 2 weeks. Desquamation of round spermatids still surrounded by a slender Sertoli cell cytoplasm was occasionally observed. A prominent change in the seminiferous tubules was an occurrence of numerous residual bodies containing one or more flagella. They were not phagocytosed by the Sertoli cell, and accumulated in the epididymal ducts. Cellular components in the epididymal lumen included degenerating round spermatids and abnormal spermatozoa and residual bodies. Although separation of the head from the tail of the spermatozoa was rarely seen, various kinds of abnormalities of flagella were frequently encountered; compact aggregation of numerous flagella in a single spermatozoon or residual body, disarrangement of mitochondrial or fibrous sheath with outer dense fibers, and fusion of flagella with a single intervening mitochondrial layer. These findings indicate that CsA gives rise to toxic effects on the spermiogenesis by impairing directly the spermiogenic cell development and by impeding Sertoli cell function including a reduction of its phagocytic activity.

Deletion mutants of the carrot phenylalanine ammonia-lyase gene promoter were used to survey cis-elements for their effect on expression of promoter activity by transient expression. Two putative cis-elements were required to give full activity, but a third might be the most important in regulation of the promoter by 2,4-dichlorophenoxyacetic acid.

In this paper, we proposed a new approach of three-dimensional (3-D) micromachining without using any masks. This approach is a direct writing using synchrotron radiation (SR) etching. Several approaches to fabricate 3-D microstructures using photo-lithography have been proposed. However, these approaches are limited to fabricate microstructures due to the using mask process. SR etching is a dry process, and the etching rate of PTFE (polytetrafluoroethylene) is so high (100 μm/min) in vacuum using the SR white light. By utilizing a high processing speed and smoothness of the etched surfaces, SR etching might have a potential for 3-D micromachining by combining the direct writing with a stage having a high degree of freedom. Here, we reported the results of 3-D micromachining of PTFE using SR etching in vacuum and examined the dependence of SR etching of PTFE on the etching environment under an atmospheric pressure of He.

Fabrication techniques of microstructures with high resolution and high aspect ratio are necessary for practical microelectromechanical systems (MEMS) that have high performance and integration. In order to fabricate microstructures with sub-micron resolution and high aspect ratio, deep X-ray lithography has been investigated using the compact synchrotron radiation (SR) light source called “AURORA”. An X-ray mask for sub-micron deep X-ray lithography, which is composed of 1 μm thick Au as absorbers, 2 μm thick SiC as a membrane and 625 μm thick Si as a frame, was designed. In preliminary experiments, the following results were achieved: EB resist microstructures with an aspect ratio of 22 corresponding with 0.07 μm width and 1.3 μm height were formed; a 10 μm thick PMMA resist containing no warp was formed by direct polymerization, enabling more precise gap control.

The prevalence of antibodies against spotted fever group rickettsia (SFGR), murine typhus and Q fever were investigated in wild rats captured in Indonesia. Sera of 327 rats were collected from Jakarta and Boyolali on Java Island. The prevalences of antibodies against SFGR and murine typhus were 128 (39.1%) and 48 (14.7%), respectively. Antibodies against Q fever were not detected in these serum samples. Antibodies against SFGR were found in all species of rats (20.8-51.9%). The antibody positive rate against murine typhus in Rattus norvegicus (38.0%) was significantly higher than that in other rat species (0-4.8%, p

We present a patient with refractory multiple myeloma who showed a good response to a combination therapy with oral melphalan, dexamethasone, and thalidomide (MDT). A 48-year-old woman with myeloma refractory to thalidomide, dexamethasone, and clarithromycin received 6 mg melphalan for 4 days every 6 weeks in combination with thalidomide (100 mg daily) and dexamethasone (5 mg daily for 2 days every week). Four months after the initiation of MDT therapy, a 78% reduction of monoclonal protein was achieved. Although the efficacy of oral MDT combination therapy in elderly patients with newly diagnosed myeloma has been reported, the present data demonstrate the effectiveness of MDT therapy for refractory myeloma and warrant further exploration with this MDT regimen to treat myeloma.

Due to the spherical shape with a diameter of ca. 1 nm, the aggregation behaviour of fullerene C60 is very interesting in view of the possible formation of magic number particle in a similar manner as metal cluster in gas phase. Herein, we report for the first time the magic number aggregation behaviours of polyhydroxylated fullerenol C60(OH)36 in water–alcohol (methanol, ethanol and 1-propanol) binary solution with increasing alcohol component. The diameters of particle were ca. 6–8 nm depending on the alcohol used. The particle sizes were precisely measured by the novel-induced grating method which is superior for the particle-size measurement in single-nano region (1–10 nm). The magic number cluster was also detected by scanning probe microscopy observation. However, such aggregation behaviours were not found in DMSO–alcohol system or for the use of less hydroxylated C60(OH)10.

FoF1-ATP synthase (FoF1) produces most of the ATP in cells, uniquely, by converting the proton motive force (pmf) into ATP production via mechanical rotation of the inner rotor complex. Technical difficulties have hampered direct investigation of pmf-driven rotation, which are crucial to elucidating the chemomechanical coupling mechanism of FoF1. Here we develop a novel supported membrane system for direct observation of the rotation of FoF1 driven by pmf that was formed by photolysis of caged protons. Upon photolysis, FoF1 initiated rotation in the opposite direction to that of the ATP-driven rotation. The step size of pmf-driven rotation was 120°, suggesting that the kinetic bottleneck is a catalytic event on F1 with threefold symmetry. The reaction equilibrium was slightly biased to ATP synthesis like under physiological conditions, and FoF1 showed highly stochastic behaviour, frequently making a 120° backward step. This new experimental system would be applicable to single-molecule study of other membrane proteins.

We have developed a facile synthetic method for highly water-soluble, hollow carbon nanoparticles with a diameter of ∼1 nm, as a so-called fullerenol. The method was extended to fullerene soot to obtain the corresponding hydrophilic carbon materials, and the products were subjected to IR and elemental analysis. Particle size analysis demonstrated the relatively high dispersion of particles with diameters of ∼70 nm, in water. The surface analysis using FE-SEM showed the difference in morphology between fullerene soot and activated carbon as well as between before and after hydrophilic treatment of the soot with hydrogen peroxide. Moreover, this hydrophilic fullerene soot exhibited high antioxidant activity as compared with fullerenol and C60.

Treatment of [Li+@C60](PF6–) with 30% fuming sulfuric acid and subsequent hydrolysis gave hydroxylated derivative Li+@C60O–(OH)7. Its structure was deduced by IR, NMR, MALDI-TOF/FAB MS, and elemental analysis. Notably, the reaction of [Li+@C60](PF6–) was site-selective, giving a single major isomer (ca. 70%) with two minor isomers, in marked contrast to the case of empty C60. Furthermore, the results clearly indicate that the internal Li cation was strongly shielded by the surface dipolar hydroxyl groups, and thus it appears that the properties of endohedral fullerenes can be controlled by the external modification of the fullerene cage. Whereas Li+@C60 is relatively insoluble, Li+@C60O–(OH)7 was found to be highly soluble in polar solvents such as DMSO and DMF. The increased solubility is especially desirable for biological/medicinal assays and applications in such research fields.

TheSelf-Mobile Space Manipulator (SM2) is a 5-DOF, 1/3-scale, laboratory version of a robot designed to walk on the trusswork and other exterior surfaces of Space Station Freedom. It will be capable of routine tasks such as inspection, parts transportation and simple maintenance and repair. We have designed and built the robot and gravity compensation system to permit simulated zero-gravity experiments. The control ofSM2 is challenging because of significant structural flexibility, relatively high friction at the joints, positioning error amplified from joint errors due to the long reach, and high performance requirements for general 3-D locomotion. In this paper, we focus on the modeling of the robot system and the design of the control system based on the model. We address the kinematics and dynamic modeling of the 3-D motion ofSM2 and demonstrate the simulation and experimental modal analysis results. The robot dynamic characteristics vary significantly when the robot configuration changes. To consider this effect, we develop a control system that is composed of two basic parts, the model-based part and the servo part. The model-based loop can be updated based on the off-line dynamic model, and the servo control loop is updated by a gain schedule according to the off-line relationship between the closed-loop frequency and the modal frequency estimated from the off-line dynamic model. By taking dynamic variation into account in the controller, the control system is independent of the robot configuration, and the motion performance ofSM2 is greatly enhanced in implementation.

The features of random chemical modification are defined with reference to acetylation of bovine hemoglobin, which has been performed in a random manner so that all of the amino groups that participate in functional chloride binding (i.e., those that are oxygen-linked) could be identified. Random chemical modification, which has objectives different from those of both specific (selective) and extensive chemical modification, has been achieved for bovine hemoglobin with the mild reagent, 14C-methyl acetate phosphate; retention of function was demonstrated by a Hill coefficient of n = 2.2 for the modified hemoglobin. After removal of unmodified Hb chains, the mixture of randomly modified acetylated alpha or beta chains was subjected to tandem treatment with trypsin and chymotrypsin. Peptides were purified by HPLC and identified by amino acid analysis. The amount of radioactivity in the acetylated amino group of a purified peptide was taken as an estimate of the degree of chloride binding. For bovine Hb, two amino groups of the alpha-chain (Val-1 and Lys-99) and three amino groups of the beta-chain (Met-1, Lys-81, and Lys-103) were shown to be oxygen-linked (i.e., to have incorporated significantly more radioactivity in the deoxy conformation compared to the same site in the oxy conformation). Three of these sites were already known chloride-binding sites [i.e., Val-1(alpha), the N-terminus of the alpha-chain, and two sites between the 2 beta-chains of bovine hemoglobin, Met-1(beta) and Lys-81(beta); these findings support the conclusions of the random modification approach. Two other chloride-binding sites, Lys-99(alpha) and Lys-103(beta), align the sides of the central dyad axis connecting the two well-known major chloride-binding sites of bovine Hb. The interrelationship of these five chloride-binding sites was assessed by improved molecular graphics. When viewed through the central dyad axis, the functional chloride-binding sites in the central cavity appear to be symmetrically related and to connect the two major chloride-binding sites. Modifiers or mutants that are directed at these regions in the central dyad axis may favor the deoxy conformation to provide a lower oxygen affinity by preventing the constriction of the central cavity that normally occurs upon oxygenation.

The diagnostic value of computed tomography (CT) as compared with conventional radiographs in the study of postoperative maxillary cysts (POMC) in 64 patients (85 sides) was evaluated. Typical CT findings of POMC were of a unilocular or multilocular homogeneous soft tissue density mass with expansile bony resorption. A comparison between conventional radiographs and CT proved that CT could determine the location and multilocularity of the cyst, the status of the antral walls, and abnormalities of the other paranasal sinuses and adjacent structures more precisely than conventional radiographs. CT also facilitated the ability to predict the direction of extension of the lesion. In conclusion CT was indispensable for accurately diagnosing POMC. In some cases the inferior extension of the lesion should be examined by conventional radiography because this can be obscured by degradation caused by metal artefacts during CT.

A compact beamline dedicated to hard x-ray deep lithography for fabrication of high aspect ratio MEMS microparts has been developed. The exposure stage was only 3 meters away from the synchrotron radiation (SR) source so that a relatively high photon flux could be achieved with a compact super-conducting SR source. The deep lithography using PMMA resist could be as deep as 1000 μm and the maximum aspect ratio achieved was about 50. The throughout for the 200 μm-deep lithography was found to be on the order of 5 cm2/h using the membrane-free mask under the routine SR conditions. Templates with the high aspect ratio microstructures have been made of the PMMA resist based on conducting substrates and applied further to electroforming to create metallic microstructures. In order to fabricate microparts for the MEMS applications, we have concentrated on development of masks for the hard x-ray deep lithography. The masks now can be made to have the 8 μm-thick gold absorber on the 2 μm-thick SiC membrane.

We inserted a long intestinal tube via the percutaneous transgastric route in three patients with an inoperable malignant bowel obstruction. The percutaneous endoscopic gastrostomy technique facilitated this method. The main purpose of our procedure is to achieve direct intestinal de-compression without nasal intubation, which is not always possible by venting gastrostomy alone. Palliative intestinal decompression proved to be effective in all patients. This alternative therapeutic strategy for managing bowel obstruction in terminal cancer patients is herein presented.

We report two cases of osteoblastoma, one of them an unusual case in a 32-year-old woman in whom a maxillary tumor was confidently diagnosed as an osteoblastoma at the time of primary excision and subsequently transformed into an osteosarcoma 7 years after the onset of clinical symptoms. The other patient developed osteosarcoma arising in the maxilla, which was diagnosed 3 years after the primary excision and is very suggestive of malignant transformation in osteoblastoma. We present the radiological features, including computed tomographic and magnetic resonance imaging studies, of this unusual event of transformed tumor and compare imaging features of benign and dedifferentiated counterparts of this rare tumor complex.