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Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

5 pages, 4 figures, supplementary materials https://doi.org/10.1126/science.abn1045.-- Data and materials availability: All data and code used in this study are openly available. RADAR data can be obtained through ESA (Sentinel) or JAXA (Alos-2). Aftershock data can be obtained from https://ayiti.unice.fr/ayiti-seismes/ (7). The codes used to process or model the data are published and public (8). The catalog of high-precision earthquake relocated with the NLL-SSST-coherence procedure (SM4) is available as supplementary data, On 14 August 2021, the moment magnitude (Mw) 7.2 Nippes earthquake in Haiti occurred within the same fault zone as its devastating 2010 Mw 7.0 predecessor, but struck the country when field access was limited by insecurity and conventional seismometers from the national network were inoperative. A network of citizen seismometers installed in 2019 provided near-field data critical to rapidly understand the mechanism of the mainshock and monitor its aftershock sequence. Their real-time data defined two aftershock clusters that coincide with two areas of coseismic slip derived from inversions of conventional seismological and geodetic data. Machine learning applied to data from the citizen seismometer closest to the mainshock allows us to forecast aftershocks as accurately as with the network-derived catalog. This shows the utility of citizen science contributing to our understanding of a major earthquake, This work was supported by the Centre National de la Recherche Scientifique (CNRS) and the Institut de Recherche pour le Développement (IRD) through their “Natural Hazard” program (E.C., S.S., T.M., B.D., F.C., J.P.A., J.C., A.D., D.B., S.P.); the FEDER European Community program within the Interreg Caraïbes “PREST” project (E.C., S.S., D.B.); Institut Universitaire de France (E.C., R.J.); Université Côte d’Azur and the French Embassy in Haiti (S.P.); the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant no. 758210, Geo4D project to R.J. and grant no. 805256 to Z.D.); the French National Research Agency (project ANR-21-CE03-0010 “OSMOSE” to E.C. and ANR-15-IDEX-01 “UCAJEDI Investments in the Future” to Q.B.); the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant no. 949221 to Q.B.); and HPC resources of IDRIS (under allocations 2020-AD011012142, 2021-AP011012536, and 2021-A0101012314 to Q.B., With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)

This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function. HJLH and DC are co-primary authors. The DAPA-CKD Trial Committees and Investigators are listed in the Appendix.

Mastication is an indispensable oral function related to physical, mental, and social health throughout life. The elderly tend to have a masticatory dysfunction due to tooth loss and fragility in the masticatory muscles with aging, potentially resulting in impaired cognitive function. Masticatory stimulation has influence on the development of the central nervous system (CNS) as well as the growth of maxillofacial tissue in children. Although the relationship between mastication and cognitive function is potentially important in the growth period, the cellular and molecular mechanisms have not been sufficiently elucidated. Here, we show that the reduced mastication resulted in impaired spatial memory and learning function owing to the morphological change and decreased activity in the hippocampus. We used an in vivo model for reduced masticatory stimuli, in which juvenile mice were fed with powder diet and found that masticatory stimulation during the growth period positively regulated long-term spatial memory to promote cognitive function. The functional linkage between mastication and brain was validated by the decrease in neurons, neurogenesis, neuronal activity, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. These findings taken together provide in vivo evidence for a functional linkage between mastication and cognitive function in the growth period, suggesting a need for novel therapeutic strategies in masticatory function–related cognitive dysfunction.

Introduction Sarcopenia is characterized by an involuntary loss of skeletal muscle mass, strength, and function. Previous studies suggest that it is generally associated with aging and chronic kidney diseases. The focus of this study was on the association between sarcopenia and pre-sarcopenia in kidney transplant recipients. Methods Fifty-one patients who underwent kidney transplantation at Kansai Medical University Hospital were enrolled, and their sarcopenia status was evaluated between April and July 2016. Sarcopenia was defined according to the criteria for the Asia Working Group for Sarcopenia. Skeletal muscle mass index was measured by using dual-energy radiograph absorptiometry; the cutoff points were Results Fifty-one recipients (36 men and 15 women) who met the inclusion criteria were enrolled in the study. The mean age of the recipients was 46.2 ± 12.8 years, and the mean duration of dialysis was 2.72 ± 3.61 years. Overall, 6 recipients (11.8%) had sarcopenia, and 25 recipients (49.0%) had pre-sarcopenia; 20 (39.2%) did not have sarcopenia. There were significant differences in age, duration of dialysis, body mass index, and triglyceride levels between the subgroups of recipients with and without sarcopenia. Multivariate regression analysis showed that age and duration of dialysis were independent variables for sarcopenic status. Conclusions Our observations indicate that age and duration of dialysis before transplantation were independent determinants of sarcopenia and pre-sarcopenia in these kidney transplant recipients.

This paper reports on the influence of underwater explosion depth on the disintegration of thin polystyrene plate attached microbubbles subjected to the underwater shock wave and the primary bubble induced by the explosion. The underwater explosion is created by the electrical discharge. The thin plate motion caused by the interaction of underwater shock wave and primary bubble with the plate is experimentally investigated and visualized by the shadowgraph method. The effect of explosion depth on the disintegration of plate is discussed by comparing visualized images. It was found that the disintegration of plate was depended on the explosion depth. It was also confirmed that the fragmentation of plate was caused not by the overpressure from microbubble collapse by the underwater shock wave loading but by the interaction of rebounding primary bubble with the plate in the experimental conditions of this study.

Background/Purpose Facial skin hyperpigmention caused by chronic sun exposure is a major skin complaint, however, its characteristics and influential factors are still limitedly known. Methods A cross-sectional survey in healthy Japanese women aged from 6 to 62 years (n=169) was conducted using a facial image analyzer VISIA™ for knowing onset age of hyperpigmented spot formation, its chronological changes, and influence of environmental factors. Results UV Pigmented Spot (PS) Score was positively correlated with age (R=.487, P=.000). Hyperpigmented spots appeared first around 18 years old in most subjects, and PS score remarkably increased at 20s then gradually increased by ages. The subjects with Skin Type I, one of the three grades of Japanese Skin Type (JST), whose melanin formation is genetically lower, showed higher PS score. A woman aged 31 years was subjected a weekly VISIA measurement for 2 years, and found no changes in the number, place, size and intensity of the pigment spots in this duration. Conclusion Hyperpigmented spots developed in women over 20 years of age due to chronic sun exposure without sun protection during childhood and adolescent and it was stable afterwards, whose intensity was influenced by age and skin type.

A new arsenic-based pincer (AsOCOAs) dehydrogenation catalyst has been synthesized, IrHCl{2,6-C6H3-(O-AsBut2)} (3). Treatment with an equivalent of base (NaO-tert-butoxide) under an atmosphere of hydrogen gas affords the dihydride catalyst IrH2{2,6-C6H3-(O-AsBut2)} (4). The activity of 3 was explored under transfer dehydrogenation conditions with cyclooctane and tert-butyl ethylene, giving a maximum turnover number of 960 at 175 °C in 24 h. Acceptorless dehydrogenations were also explored with pyrrolidine-based molecules, ethylperhydrocarbazole (5), methylperhydroindole (6), and butylpyrrolidine (7), in which all results indicate 3 is roughly half as active as the analogous phosphine-based pincer catalyst 2. Akin to the phosphine pincer catalysts the activity was seen to steadily improve with increasing temperature, peaking at 175 °C, upon which thermal decomposition sets in.

Background Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large-scale, randomized, placebo-controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). Methods FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo-controlled, parallel-group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. Key Results Two hundred forty-seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori-infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori-uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori-positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. Conclusions & Inferences Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954).

Background and purpose: GLA is the causative gene of Fabry disease, an X-linked lysosomal storage disorder resulting from a-galactosidase A (a-GAL) deficiency. Stroke is an important manifestation of Fabry disease, and recent epidemiological studies have indicated that up to 4.9% of young male cryptogenic stroke patients have GLA mutations. To determine the importance of GLA mutations in the general stroke population, the frequency of GLA mutations in Japanese male ischaemic stroke (IS) patients with various risk factors and ages was measured. Methods: A total of 475 male IS patients (mean age 69.7 12.5 years), were enrolled in this study. A blood sample was obtained to produce blood spots for measurement of a-GAL activity. Blood samples with decreased enzymatic activity were reassayed and the entire GLA gene was analyzed by direct DNA sequencing if a-Gal A activity was consistently low. Results: a-Gal A activity was decreased in 10 men, five of whom (1.1%) had the GLA gene mutation, p.E66Q. All IS patients with p.E66Q mutation had substantial residual a-Gal A activity, in contrast to patients with classic-type Fabry disease. Clinically, all patients with p.E66Q mutation were > 50 years old and had multiple small-vessel occlusions (lacunar infarctions). Statistical analysis using Fisher’s exact test showed the allele frequency of GLA p.E66Q in patients with small-vessel occlusion to be significantly higher than that in the general Japanese population [odds ratio (OR) = 3.34, P = 0.025). Conclusions: GLA p.E66Q mutation is a genetic risk factor for cerebral small-vessel occlusion in elderly Japanese males.

Lightweighting of automobile vehicle is a significant application trends, using magnesium alloy wheels is a valuable way. This article discusses design of a new model of automobile wheel. Then bending test and radial test finite element model were established. Considering three different materials namely magnesium alloy, aluminium alloy and steel, the stress and strain performances of each material can be obtained. Through evaluating and analyzing model in bending test and radial test, we obtained the reasonable and superior results for magnesium alloy wheel. The results of the equivalent stress and deformation were compared, the magnesium alloy wheel practicality has been confirmed. This research predicts the reliability of the structural design, some valuable references are provided for the design and development of magnesium alloy wheel.

A robust non-linear output-feedback controller by the K-filter approach is proposed for position-tracking problem of a magnetic levitation system, where only the position measurement is available for control. Instead of the popular adaptive control techniques, a disturbance observer (DOB) is merged into the K-filter-based output-feedback controller to compensate the external disturbance and model mismatch, so that a much simpler controller is constructed. Rigorous stability of the non-linear control system is established. Experimental results are included to show the excellent performance of the designed controller.

MgB2 multifilamentary tapes with 6 twisted filaments were fabricated and it was experimentally proven that both an increase in critical currents and a decrease in ac losses in the tapes due to deformation of the tapes with high aspect ratio can be simultaneously attained. This will improve the performance of MgB2 wires for the new conductors as windings of superconducting coils with both low losses and high stability for fusion reactors, superconducting magnetic energy storage systems, and so on. There are three kinds of prepared samples in which one sample is a round wire of 1.02 mm in diameter and other samples are tapes obtained by the rolling process from the round wire. The aspect ratios of these tapes are 3.3 and 6.6. These wires are composed of MgB2/Nb/CuNi . The 6 filaments are twisted with twist pitches of 50 mm. The measurements of critical currents and coupling losses were carried out at 4.2 K. The observed critical current densities of the tapes are two times larger than that of the round wire under the external magnetic fields of 2 T to 7 T in a direction parallel to the flat faces of the tapes. The observed coupling losses in the tape with aspect ratio of 6.6 were 1/10 smaller than that of the round wires, where the parallel magnetic fields were applied to the flat faces of the tapes.

In order to investigate the crack path under Mode II or Mode III loadings, reversed torsion tests were carried out on SAE52100 and Mode II fatigue crack growth tests were carried out on 0.47% carbon steel specimens. In the torsional fatigue test (SAE52100), the type of inclusion at the torsional fatigue fracture origin was slender MnS inclusions which were elongated in the longitudinal direction. The cracks first propagated by Mode II up to crack length 2a = 100–200 μm (which are almost equal to the length of MnS inclusion) in the longitudinal direction, and then branched by Mode I to the direction (∼ ± 70.5°) perpendicular to the local maximum normal stress (σθmax) at the crack tip. In the Mode II fatigue crack growth test (0.47% carbon steel) in air and in a vacuum, the cracks first propagated by Mode II. After the Mode II fatigue crack growth stopped, the crack branched to the direction perpendicular to the local maximum normal stress (σθmax) at the crack tip, and finally branched to the angle close to the direction perpendicular to the remote maximum principal stresses. A fibrous pattern on the Mode II fatigue fracture surface tested in a vacuum was clearer than that in air. The Mode II threshold stress intensity factor ranges, ΔKIIth = 10.2 MPa m (Longitudinal crack) and ΔKIIth = 12.5 MPa m (Transverse crack) in a vacuum were higher than those in air, ΔKIIth = 9.4 MPa m (Longitudinal crack) and ΔKIIth = 10.8 MPa m (Transverse crack). Both in vacuum and in air, the values of ΔKIIth for crack growth perpendicular to the rolling direction were higher than those for crack growth parallel to the rolling direction. The values of KII and KIII at a 3D elliptical crack tip under shear stress were analyzed to investigate the shear crack growth pattern in materials. The 3D crack analysis shows that the most stable aspect ratio b/a of a small planar elliptical crack under cyclic shear stress is b/a = 0.49 in absence of friction on the crack surfaces. The aspect ratio b/a = 0.49 can be explained by the equal resistance against fatigue crack growth both in Mode II and Mode III, i.e., ΔKIIth = ΔKIIIth. However, the aspect ratio b/a for the failure of a real railway wheel did not stay at the stable aspect ratio b/a = 0.49 and continued decreasing. The cause for the decrease in the aspect ratio b/a smaller than 0.49 was revealed to be the friction between crack surfaces.

Summary Background The inhibitory effect of probiotic bacteria on atopic dermatitis has been shown in human infants, but the mechanism is still unclear. Objective This study aimed to show the effects of the administration of a probiotic during the weaning period in mouse models on production of the intestinal secretory IgA (sIgA) and on the development of atopic dermatitis (AD) in later life. Methods The effects of the administration of Lactobacillus johnsonii NCC533 (La1) during weaning were evaluated using a mouse model (Balb/c). The weaning period of mice was divided into three phases according to the evolution of faecal IgA. La1 was administered in each phase and the evolution of the faecal IgA was estimated. In the next experiment, the effect of the administration of La1 in phase 2 on host immunity after maturation was further assessed by using the model NC/Nga mouse for human AD. Results Administration of La1 in each phase showed a distinct effect on the production of sIgA. But sIgA production was only positively stimulated when La1 was administrated in phase 2. The development of AD induced by mite antigen from 6 weeks old was significantly prevented by the primary administration of La1 in phase 2. AD-like lesions were significantly milder than those of the control mice, and histological observations showed an almost normal appearance of the epidermis and upper dermis of the mice treated with La1. Conclusion This study suggested that the primary administration of La1 in a specific part of the weaning period is effective in preventing or inhibiting the development of AD after maturation by modulating or accelerating the gut immune response.

Carbon fiber reinforced plastics (CFRP) are attracting attention in the automotive industry due to their light weight. Thermoset plastics like epoxies are mainly used as matrices of CFRP in that industry. The curing time of the thermosetting resin is long thus leading to poor productivity. Within thermoplastic resins, polycarbonate (PC) is excellent for its impact properties; consequently, it is expected to be used as the matrix of composite materials for automotive structures. Moreover, in order to obtain outstanding strength, the application of continuous fibers as reinforcement is anticipated. However, large-scale equipment is needed and the work of press load is required in order to impregnate PC into continuous fibers. Recently, unidirectional (UD) tapes of CF/PC in which the PC matrix was impregnated into a CF bundle have been developed. In this study, carbon fiber reinforced polycarbonate (CF/PC) was moulded using UD tapes and the practicality of UD tape was examined by studying its mechanical properties aiming at shortening the moulding time.

The growth of Cu nanostructures on the hydrogen-terminated Si(111) surface was studied by scanning tunnelling microscopy (STM). On the hydrogen-terminated Si(111) surface, small Cu nanostructures scatter mainly on the terraces and a few structures along the steps and domain boundaries at a deposition temperature of ∼310°C: the shape of the nanostructure is round or triangular, and the face is not clear. At ∼340°C, the Cu nanostructures form preferentially at steps and domain boundaries of the substrate: the shape is triangular with truncated corners and the nanostructures have some facets. The top face has an inclination angle of ∼6° and the side face has one of ∼35°. On the top face, mono-atomic steps can be seen ∼0.8 nm apart. From these results, it is concluded that the Cu nanostructure has a {554} facet on top and a {110} facet on the side. Copyright © 2003 John Wiley & Sons, Ltd.

This paper describes the 32-Mb and the 64-Mb embedded DRAM core with high efficient redundancy, which is fabricated using 0.13-/spl mu/m triple-well 4-level Cu embedded DRAM technology. Core size of 18.9 mm/sup 2/ and cell efficiency of 51.3% for the 32-Mb capacity, and core size of 33.4 mm/sup 2/ and cell efficiency of 58.1% for the 64-Mb capacity are realized. This core can achieve 230-MHz burst access at 1.0-V power-supply condition by adopting a new data bus architecture: merged shift column redundancy. We implemented four test functions to improve the testability of the embedded DRAM core. It realizes the DRAM core test in a logic test environment.

The building of a demonstration fast breeder reactor (DFBR) plant in Japan is planed to be base isolated in the horizontal direction. To verify the seismic safety of the isolation system, a series of shaking table tests was conducted using a reduced scale model with three types of base isolation system, natural rubber bearing with steel damper (NRB + SD), lead rubber bearing (LRB), and high damping rubber bearing (HRB). The results of these tests showed NRB + SD, LRB and HRB were within the stable domain (not hardening) at 1 x S2 (maximum acceleration 3.80 m S 2 ) input, and were nearly hardening at 2 x S2 input. None of the rubber bearings broke at 3 x S2 input, which was the design limit. All these bearings broke at over 4 x S2 input.

Background: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19. Aim: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C19 genotypic status. Methods: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n=5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner. Results: The relative values for the area under the serum concentration–time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively. Conclusion: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.

This paper describes a 32-Mb embedded DRAM macro fabricated using 0.13-/spl mu/m triple-well 4-level Cu embedded DRAM technology, which is suitable for portable equipment of MPEG applications. This macro can operate 230-MHz random column access even at 1.0-V power supply condition. The peak power consumption is suppressed to 198 mW in burst operation. The power-down standby mode, which suppresses the leakage current consumption of peripheral circuitry, is also prepared for portable equipment. With the collaboration of array circuit design and the fine Cu metallization technology, macro size of 18.9 mm/sup 2/ and cell efficiency of 51.3% are realized even with dual interface and triple test functions implemented.

Recent multimedia applications and personal computers require enhanced memory systems. 3D-graphics and networking require faster random cycle and lower latency megabit-scale RAMs. However, the random cycle time of conventional DRAM is too slow and embedded SRAM area is too large to integrate high-density RAM on a chip. The fast random cycle low-latency embedded RAM macro reported here uses a dual-port interleaved DRAM architecture (D/sup 2/RAM). D/sup 2/RAM reduces random cycle time from 50 ns (20 MHz) of conventional DRAM to 8 ns (125 MHz) on a test chip with a 0.25 /spl mu/m embedded DRAM process. Key technologies are (1) interleaved open bitline operation with dual-port memory cell architecture, (2) two-stage pipelined circuit operation and (3) write before sensing (WBS).

We report on results of a search for the decay mode K_L -> pi^0 gamma e^+ e^- conducted by the E162 experiment at KEK. We observed no events and set a 90% confidence level upper limit of Br(K_L -> pi^0 gamma e^+ e^-)< 7.1x10^{-7} for its branching ratio. This is the first published experimental result on this decay mode.

Short-channel effects (SCE) in ultrathin silicon-on-insulator (SOI) fully depleted (FD) MOSFETs are analyzed and an analytical model for threshold voltage, including the kink effect, is presented. The proposed model accounts for (1) a general nonuniform channel doping profile, (2) the drain-induced V/sub th/- lowering enhancement resulting from the interaction of (a) impact ionization, (b) floating-body, and (c) parasitic-bipolar effects. Good agreement between the proposed model and experimental data is demonstrated. Impact ionization and floating-body effects dominate V/sub th/ lowering for drain voltages larger than V/sub dk//spl sime/B/sub i/./spl lambda//sub i//3, where B/sub i/ is the impact ionization coefficient, and /spl lambda//sub i/ is the impact ionization length, a structural parameter which, for a single-drain SOI MOSFET, coincides with the SCE characteristic length /spl lambda/.

Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(–)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(–)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+) / VEGF-189(–) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189. © 1999 Cancer Research Campaign

We report on results of an experimental search for the K_L -> pi^+ pi^- e^+ e^- decay mode. We found 13.5 +- 4.0 events and determined its branching ratio to be (4.4 +- 1.3(stat) +- 0.5(syst))*10^{-7}. The result agrees well with the theoretical prediction.

The Core Project Biospheric Aspects of the Hydrological Cycle (BAHC) of the International Geosphere Biosphere Programme (IGBP) addresses the biospheric aspects of the hydrological cycle through experiments and modelling of energy, water, carbon dioxide and sediment fluxes in the soil– vegetation–atmosphere system at a variety of spatial and temporal scales. Active regulation of water, energy and carbon dioxide fluxes by the vegetation make it an important factor in regulating the Earth’s hydrological cycle and in the formation of the climate. Consequently, human induced conversion of vegetation cover is an important driver for climate change. A number of recent studies, discussed in this paper, emphasise the importance of the terrestrial biosphere for the climate system. Initially, these studies demonstrate the influence of the land surface on tropical weather and climate, revealing the mechanisms, acting at various scales, that connect increasing temperatures and decreasing rainfall to large-scale deforestation and other forms of land degradation. More recently, the significance of the land surface processes for water cycle and for weather and climate in temperate and boreal zones was demonstrated. In addition the terrestrial biosphere plays a significant role in the carbon dioxide fluxes and in global carbon balance. Recent work suggests that many ecosystems both in the tropics and in temperate zones may act as a substantial sink for carbon dioxide, though the temporal variability of this sink strength is yet unclear. Further, carbon dioxide uptake and evaporation by vegetation are intrinsically coupled, leading to links and feedbacks between land surface and climate that are hardly explored yet. Earth’s vegetation cover and its changes owing to human impact have a profound influence on a lateral redistribution of water and transported constituents, such as nutrients and sediments, and acts therefore as an important moderator of Earth’s biogeochemical cycles. In the BAHC science programme, the importance of studying the influence of climate and human activities on mobilisation and river-borne transport of constituents is explicitly articulated. The terrestrial water and associated material cycles are studied as highly dynamic in space and time, and reflect a complex interplay among climatic forcing, topography, land cover and vegetation dynamics. Despite a large progress in our understanding of how the terrestrial biosphere interacts with Earth’s and climate system and with the terrestrial part of its hydrological cycle, a number of basic issues still remain unresolved. Limited to the scope of BAHC, the paper briefly assesses the present status and identifies the most important outstanding issues, which require further research. Two, arguably most important outstanding issues are identified: a limited understanding of natural variability, especially with respect to seasonal to inter-annual cycles, and of a complex ecosystem behaviour resulting from multiple feedbacks and multiple coupled biogeochemical cycles within the overall climate system. This leads to two major challenges for the future science agenda related to global change research. First, there is a need for a strong multidisciplinary integration of research efforts in both modelling and experiments, the latter extending to inter-annual timescales. Second, the ever increasing complexity in characterisation and modelling of the climate system, which is mainly owing to incorporation of the biosphere’s and human feedbacks, may call for a new approach in global change impact studies. Methodologies need to be developed to identify risks to, and vulnerability of environmental systems, taking into account all important interactions between atmospheric, ecological and hydrological processes at relevant scales. With respect to the influence of climate and human activities on mobilisation and river-borne transport of constituents, the main issues for the future are related to declining availability and quality of ground data for quantity and quality of water discharge. Such assessments as presented in this paper, in combination with community wide science evaluation, have lead to an update of the science agenda for BAHC, a summary of which is provided in the appendix.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been suggested to be involved in the carcinogenesis of some types of tumours by autocrine or paracrine mechanisms. We examined GM-CSF/GM-CSF receptor (GM-CSFR) gene expression in 20 human non-small cell lung cancer (NSCLC) xenografts. The stimulatory effects of GM-CSF were examined using GM-CSF transgenic severe combined immunodeficient (SCID) mice (GM-Tg-SCID), which produce abundant human GM-CSF. A NSCLC xenograft (LC11-JCK), expressed GM-CSFR but not GM-CSF, and showed more rapid growth in GM-Tg-SCID than non-GM-CSF transgenic SCID mice (non-Tg-SCID). GM-CSF gene expression was detected in 48 of 90 (53%) primary NSCLC human specimens and GM-CSFR gene expression was detected in 42 specimens (47%). GM-CSF expression was detected in 13 of 30 squamous cell carcinoma specimens (43%) and GM-CSFR expression was detected in 10 specimens (33%). Patients with squamous cell carcinoma coexpressing GM-CSF and GM-CSFR showed significantly poorer prognosis than those expressing neither GM-CSF nor GM-CSFR (P < 0.05, Cox-Mantel test). These results suggest that GM-CSF can have a stimulatory effect on some NSCLC.

The present study was to investigate whether pituitary adenylate cyclase activating polypeptide (PACAP) can modify norepinephrine (NE) release in response to pancreatic nerve stimulation in anesthetized dogs. Plasma catecholamine concentrations in aortic and superior pancreaticoduodenal (SPD) venous blood were determined by a high performance liquid chromatography method. SPD venous blood flow was measured with an electromagnetic flowmeter. Pancreatic nerves were directly stimulated for 1 min (2 ms, 12 V) at various frequencies at the level of the SPD artery. Various doses of PACAP1-27 (PACAP27) were locally infused into the pancreas through the SPD artery. Nerve stimulation significantly increased both SPD venous NE concentration and its output from the pancreas in a frequency-dependent manner. With PACAP27 alone, neither SPD venous NE concentration nor its output changed significantly following the local administration of PACAP27 at any dose tested. In the presence of PACAP27, however, the net increases in NE concentration and its output in response to nerve stimulation at 2 Hz were significantly enhanced in a dose-dependent manner. The enhanced NE responses to nerve stimulation by PACAP27 were thus significantly greater than those obtained from the group receiving either PACAP27 or stimulation alone. Increases in NE concentration and its output induced by local administration of tyramine were virtually abolished by desipramine, a neural amine uptake inhibitor. However, the NE response to tyramine was not diminished by PACAP27. The results indicate that PACAP27 enhances the stimulation-induced NE release in the pancreas, and that this facilitatory effect of PACAP27 does not result from an inhibition of the neural amine uptake mechanism. The study suggests that PACAP receptor-mediated mechanisms may be involved either directly or indirectly in the local modulation of neural NE release in the canine pancreas in vivo.Key words: presynaptic, sympathetic nerve, neuropeptide, tyramine, reuptake, anesthetized dog.

To study one-dimensional (1D) quantum liquid of4He, we measured the heat capacity and performed a torsional oscillator experiment for4He adsorbed on a new mesoporous substrate whose adsorption area consists of walls of straight one-dimensional 18A diameter tunnels. The presence of adsorbed quantum liquid was examined by the isotope effect on the heat capacity for3He and4He adatoms. Above a coverage no, the heat capacity isotherms are completely different because of the Fermi and the Bose fluids, respectively. In the torsional oscillator experiment we observed superfluid4He above no. The fraction of the superfluid decoupled from the motion of the substrate is 0.13, which is the same order as 0.18 for packed Pt fine powder and 0.24 for 80 A-porous glasses. The result indicates that the superfluid state exists in the one-dimensional4He adatoms formed in the 18 A diameter pores.

In order to numerically evaluate the water discharge property of the Jiulianshan river basin, we applied the hydrologic cycle model (HYCYMODEL) to the discharge response to rainfall observed in the Jiulianshan river basin. The parameters in this model were optimized by trial and error. Monthly potential transpiration rate was computed from observed air temperature, humidity, and solar radiation with Priestly-Taylor equation. The discharge response to the rainfall simulated using HYCYMODEL agreed well with the observed discharge. The estimated parameters and the result of simulation of the discharge response to the rainfall were compared with those reported for the typical Japanese temperate forest river basins. In Jiulianshan, the ratio of the impermeable area is small, and the river basin has a large capacity of water storage. As a result, it was found that the shape of hydrograph of Jiulianshan river basin is different from those of Japanese river basins, although the ratio of total base flow to the total discharge is similar to those of Japanese river basins. In Jiulianshan, the peak of discharge is smaller and the recession hydrograph is more gentle.

The polarization of tau leptons in the reaction e+ e- --> tau+ tau- has been measured using a e+e- collider, TRISTAN, at the center-of-mass energy of 58 GeV. From the kinematical distributions of daughter particles in tau --> e nu nu-bar, mu nu nu-bar, rho nu or pi(K) nu decays, the average polarization of tau- and its forward-backward asymmetry have been evaluated to be 0.012 +- 0.058 and 0.029 +- 0.057, respectively.

Measurements are reported of the thermo-e.m.f. of a thermoelectric junction composed of polycrystalline ferrites or multilayered ferrite films as a function of the temperature. The thermo-e.m.f. of the bulk and ferrite films was much larger than that of the conventional thermoelectric junction made of metals. A positive or negative thermoelectric power was observed depending on the difference in the combination of ferrites. The temperature dependence was almost linear from room temperature up to about 500°C and above which it showed a tendency to saturate. Application of a magnetic field had a reducing effect upon the thermo-e.m.f. at temperature of room to the Curie temperature.

We have developed a new type of laparoscope with flexible view point. This system can move the view without moving laparoscope itself. To achieve the wide range of view moving, we used a commercial 30° oblique-viewing laparoscope and special lens. The system control the view by rotating the oblique-viewing laparoscope and a sleeve which is attached to the special lens by motors independently. From the evaluation experiments, we confirmed the laparoscope which has 70° view angle could move the view ±60°. In the image quality evaluation experiment, degradation of the image quality was small. The positioning accuracy was 2.4±1.7 mm repeatability was 0.48 mm which lead to precise view control. The system achieve the safe and smooth manipulation of the laparoscopic view.