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Accumulation and concentration of debris in deep hole electrical discharge machining (EDM) significantly hinder its machining efficiency and accuracy. It is believed that the movement of bubbles associated with the discharge gap flow field play a pivotal role in debris removal and influence the discharge conditions. Ultrasonic vibration (USV) of the electrode is thought to be an effective method for improving EDM-generated bubbles and debris exclusion. In this study, we first elucidated the behavior of bubbles during EDM of holes with varying aspect ratios. Subsequently, USV was introduced to EDM. The behavior of dielectric fluid flow under the influence of ultrasonic vibration was analyzed using computational fluid dynamics (CFD), which revealed time-varying changes in discharge gap flow pressure and velocity. The velocity of the dielectric flow field near the electrode's side face was found to reach a maximum of approximately 15.2 m/s, greatly facilitating debris removal. High-speed camera observations revealed that bubbles were dispersed within the side gap, with most of them adhering to the electrode's wall. Furthermore, the bubbles exhibited a tendency to continuously break up and coalesce near the hole's outlet before escaping in the USV-assisted EDM. These observed characteristics of bubble behavior under the influence of USV are expected to significantly enhance debris removal and promote efficient dielectric exchange. [ABSTRACT FROM AUTHOR]

This paper deals with a non-destructive analysis of residual stress through the visualization of deformation behaviors induced by a local spot heating. Deformation was applied to the surface of an aluminum alloy with an infrared spot laser. The heating process is non-contact, and the applied strain is reversible in the range of room temperature to approximately +10 °C. The specimen was initially pulled up to elastic tensile stress using a tensile test machine under the assumption that the material was subject to the tensile residual stress. The relaxation behaviors of the applied strain under tensile stress conditions were evaluated using contact and non-contact methods, i.e., two strain gauges (the contact method) and a two-dimensional electronic speckle pattern interferometer (non-contact method). The results are discussed based on the stress dependencies of the thermal expansion coefficient and the elasticity of the materials. [ABSTRACT FROM AUTHOR]

The rotary friction welding (RFW) is a robust, precise, productive and economical joining process that is used in many areas of mechanical engineering to produce lightweight structures consisting of combinations of ferrous and non-ferrous materials, for instance aluminium alloy and steel. Crucial for the design of such lightweight structures is the knowledge about the bonding strength. The bonding strength is the result of the bond formation depending on the present transient kinematic, kinetic and thermal states during the welding process being directly determined by the welding process parameters. Despite several years of empirical research, no reliable numerical modelling approach exists for the RFW process to analyse the bonding strength based on these transient state variables. For this reason, an improvement of the bond formation and therefore an increase in the bonding strength can only be tested experimentally. The main motivation of this paper is to develop an appropriate modelling approach for the estimation of the bonding strength for friction welded lightweight structures manufactured of an aluminium alloy and a structural steel. Therefore, a couple of aluminium alloy and steel welding experiments with different process parameters were performed and subsequently analysed concerning to the resulting bonding strength. Moreover, all the welding experiments were simulated in regard to the corresponding welding process in order to determine the present kinematic, kinetic and thermal state variables, like the strain rate, the stress and the temperature. Thus, a model for the characterization of the bond formation can be developed, which allows a correlation between the bond formation and the resulting bond strength based on the chosen welding process parameters. Finally, the model will be examined and discussed in terms of its plausibility and applicability. • Process simulation of friction welded lightweight structures made of aluminium alloy and structural steel. • Estimation of the transient kinematic, kinetic and thermal state variables in the welding contact zone. • Detailed derivation of a numerical modelling approach to analyse the bonding strength based on the state variables. • Experimental validation. [ABSTRACT FROM AUTHOR]

A transitional stage in the relative motion was confirmed through in-situ observation using a high-speed camera and digital image correlation. In the earlier bonding time within the first 20 ms, relative motion predominantly occurred between the bonding materials, resulting in the formation of an initial bond at the bonding interface. The initial bond developed toward the vibration direction with increasing bonding time. The formation of a larger bonded region was observed at larger edge angles, resulting in greater joint strength. In the latter stage of bonding time beyond 50 ms, the relative motion between the tool edge and the bonding material became predominant because of bond formation at the bonding interface. The relative motion between the bonding tool and the bonding material caused macroscopic plastic flow in the bonding part when larger edge angles were used, leading to the observed increase in joint strength. The enhancement of bond creation at larger edge angles is discussed on the basis of finite element analysis focusing on the change in stress distribution at the bonding interface with the penetration of the tool edge. [ABSTRACT FROM AUTHOR]

Ultrasonic vibration was applied to a single AA1050 aluminum sheet, and relative motion between a weld tool and a specimen during ultrasonic welding was assessed. Weld tools with different knurled edges such as a trapezoidal pattern edge (trapezoidal edge) and a serrated pattern edge (serrated edge) were prepared in this study to investigate the effect of tool edge geometry on weld microstructure. Relative motion behaviors between weld tools and a specimen were analyzed with a high-speed camera and digital image correlation. A large difference was observed under the normal force of 588 N. In this condition, relative amplitude of the serrated edge was larger than that of the trapezoidal edge, and the penetration of the serrated edge was lower than that of the trapezoidal edge. In the serrated edge, plastic flow in the microstructure occurred because of a greater temperature rise. The strength of the joints welded using the serrated edge was greater than that using the trapezoidal edge. In addition, although smaller relative vibration was observed in both of the tool edges as the normal force increased, the serrated edge showed higher joint strength. These phenomena are discussed and related to the relative amplitude and penetration depth. It is suggested that the bonded area was enlarged by the plastic flow, thereby increasing joint strength. [ABSTRACT FROM AUTHOR]

Abstract: Coating of aluminide on a TiAl-based alloy (49.1at.% Al) was carried out by thermal spraying pure aluminum and subsequent diffusion treatment at 1100°C. The growth of a Ti–Al intermetallic layer in the coating layers during diffusion treatment for 120–1800s as well as the oxidation resistance of the aluminized TiAl-based alloy was investigated. The outermost surface layer was comprised of Al-rich intermetallic TiAl3 and contained pores. In contrast, an Al concentration gradient layer consisting of Ti2Al5, TiAl2, and Al-rich TiAl containing 55at.% Al was formed between the outermost layer and the substrate. The thickness of the outermost layer decreased with increasing diffusion time, while the thickness of the intermediate layer grew to approximately 30μm. In addition, the coating/substrate interface changed from a wavy to a linear form with the growth of the intermediate layer. The aluminized coating, at all diffusion times, showed good oxidation resistance in cyclic oxidation tests at 900°C in air. [Copyright &y& Elsevier]

The aims of this study were to develop a population pharmacokinetic (PPK) model for pravastatin pharmacokinetics with regard to enterohepatic circulation (EHC) and to evaluate effects of polymorphisms in SLCO1B1 and ABCC2 on the pharmacokinetic (PK) profile of pravastatin quantitatively. A total of 636 blood samples from 57 healthy male volunteers were used. The PPK analysis was carried out using nonlinear mixed effect modeling (NONMEM) and validated by a bootstrap analysis. The PK profile of pravastatin was best described by a model of EHC with Erlang's distribution. A covariate analysis revealed that SLCO1B1*15 significantly influenced relative bioavailability (Frel); Frel was increased 1.50- and 1.95-fold in participants heterozygous and homozygous, respectively, for the *15 allele in comparison with participants without the allele. No ABCC2 polymorphism was identified as a potential covariate for pravastatin. The bootstrap analysis indicated that the PK profile of pravastatin was adequately described by the proposed PPK model. SLCO1B1*15 has a significant effect on Frel, indicating that OATP1B1 is one of the determinants of systemic exposure to pravastatin. [ABSTRACT FROM AUTHOR]

Abstract: The dissociation mechanism of excited CH2X2 (X=Cl, Br) was investigated using charge-inversion mass spectrometry, in which positive ions collide with an alkali metal target to generate neutral fragments, and the negative ions formed from the neutral fragments are mass analyzed. Different relative abundances of the negative ions were observed in the charge-inversion spectra for CH2Cl2 and CH2Br2. The kinetic energy release values calculated from analysis of the peak associated with in the charge-inversion mass spectrum of the parent ion indicate that the excited CH2Cl2 formed by neutralization dissociates spontaneously into CHCl2 +H. [Copyright &y& Elsevier]

Abstract: The machinability of high-temperature aluminized steel, wherein hot-dip aluminum-coated steel is heated to 1000°C, was investigated by machining the material using a cemented carbide tool. It was confirmed that the alloy layer formed by the high-temperature aluminizing consisted of an Fe2Al5 layer, an FeAl layer and an aluminum solid solution (αFe(Al)). With increasing diffusion time, the thickness of the FeAl layer and the αFe(Al) layer increased while the thickness of the Fe2Al5 layer decreased. During the machining of the aluminized steel at a cutting speed of 1.5m/s, the tool temperature rose rapidly, in particular during cutting of the FeAl layer. Flank wear during cutting of the Fe2Al5 layer was not greatly affected by changing the cutting speed. In contrast, flank wear during cutting of FeAl was smaller at a lower cutting speed. The machined surface roughness was larger for cutting of the Fe2Al5 layer and the FeAl layer region because of brittle fracture on the machined surface, whereas it decreased with increasing distance from the surface to a minimum at the αFe(Al) layer region. [Copyright &y& Elsevier]

Abstract: Foil aluminizing of steel, wherein Al diffuses to the base steel material by diffusion treatment after hot pressing of the aluminum foil at a lower temperature than the melting point, was performed in this study. Alloy layers formed by diffusion at temperatures ranging from 700 to 1000 °C were investigated, and their features were compared with those of hot-dip aluminized steel. In hot-dip aluminizing, an intermediate Fe2Al5 layer was formed between the aluminum layer and the base steel during aluminum coating before the diffusion treatment. In contrast, the coating layer of the foil-aluminized steel specimen after diffusion bonding of the aluminum foil consisted only of the Al layer. An Fe2Al5 layer, an FeAl layer and an Al diffused layer were formed in both the aluminized specimens subsequent to the diffusion treatment. The numbers of voids formed in the Fe2Al5 layer and at the FeAl/Al diffused layer interface of the foil-aluminized specimens are smaller than those for hot-dip aluminizing. Moreover, the FeAl and Al diffused layers are formed with a greater thickness in the foil-aluminized steel under identical diffusion conditions. The Al concentration in hot-dip aluminized steel decreased in stages from the surface to the base steel, whereas, in the foil-aluminized steel, it decreased gradually. The Fe2Al5/base steel interface in the foil-aluminized steel was thus indistinct, and cross-sectional hardness also decreased gradually. [Copyright &y& Elsevier]

Patients with non-dialysis chronic kidney disease (CKD) are at greater risk of early mortality and decreased physical function with an advance in the stage of CKD. However, the effect of exercise in these patients is unclear. This meta-analysis aimed to determine the effects of physical exercise training on the risk of mortality, kidney and physical functions, and adverse events in patients with non-dialysis CKD. The meta-analysis conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the Cochrane Handbook recommendations. On 16 August 2019, the PubMed, CINAHL, Cochrane Library databases, and Embase were electronically searched, with no restrictions for date/time, language, document type, or publication status, for eligible randomized controlled trials (RCTs) investigating the effects of exercise on mortality and kidney and physical function in patients with non-dialysis CKD. Eighteen trials (28 records), including 848 patients, were analyzed. The effects of exercise on all-cause mortality and estimated glomerular filtration rate were not significantly different from that of usual care. Exercise training improved peak/maximum oxygen consumption compared to usual care. Regular exercise improves physical and walking capacity for patients with non-dialysis CKD. Effect on leg muscle strength was unclear. [ABSTRACT FROM AUTHOR]

A method to diagnose the deformation status of solid objects under loading is discussed. The present method is based on a recent field theory of deformation and fracture and optical interferometry known as the Electronic Speckle-Pattern Interferometry (ESPI). Using one of the most fundamental principles of physics referred to as symmetry in physics, this field theory formulates all stages of deformation and fracture on the same theoretical basis. In accordance with the formalism, the theory has defined the criteria for different stages of deformation (linear elastic, plastic and fracturing stages) expressed by certain spatiotemporal features of the differential displacement (the displacement occurring during a small time interval). The ESPI is used to visualize the differential displacement field of a specimen as two-dimensional, full-field interferometric fringe patterns. This paper reports experimental evidence that demonstrates the usefulness of the present method. A tensile load is applied to an aluminum-alloy plate specimen at a constant pulling rate and the resultant in-plane displacement field is visualized with a two-dimensional ESPI setup. The differential displacement field is obtained at each time step and the interferometric fringe patterns are interpreted based on the criterion for each stage of deformation. It has been found that the criteria of linear elastic deformation, plastic deformation and fracturing stage are clearly observed in the corresponding fringe patterns and that the observations are consistent with the loading characteristics. [ABSTRACT FROM AUTHOR]

This paper discusses a non-destructive measurement technique of residual stress through optical visualization. The least amount of deformation possible is applied to steel plates by heating the specimens +10 °C from room temperature for initial calibration, and the thermal expansion behavior is visualized with an electronic speckle pattern interferometer sensitive to two dimensional in-plane displacement. Displacement distribution with the thermal deformation and coefficient of thermal expansion are obtained through interferometric fringe analysis. The results suggest the change in the thermal deformation behavior is affected by the external stress initially applied to the steel specimen. Additionally, dissimilar joints of steel and cemented carbide plates are prepared by butt-brazing. The residual stress is estimated based on the stress dependence of thermal expansion coefficient. [ABSTRACT FROM AUTHOR]

This study is aimed at developing an anisotropic elastoplastic constitutive model for geomaterials at finite strain and its stress calculation algorithm based on the fully implicit return‐mapping scheme. The Cam‐clay plasticity model is adopted as a specific prototype model of geomaterials. As a pertinent representation of deformation‐induced anisotropy in geomaterials, nonlinear rotational hardening is incorporated into the model in a theoretically reasonable manner by introducing the dual multiplicative decompositions of the deformation gradient tensor. In addition to the usual decomposition into elastic and plastic parts, the plastic part is decomposed further into a part contributing to the rotational hardening and a remainder part. The former part leads to a back stress ratio tensor related to the rotational hardening via a hyperelastic‐type hardening rule. The constitutive theory is thereby formulated on proper intermediate configurations entirely in terms of deformation‐like tensorial variables possessing invariance property, without resort to any objective rates of stress or stress‐like variables. Combining the Cam‐clay plasticity with the concept of subloading surface, a class of unconventional plasticity, enables the model to be capable of reproducing complex hardening/softening accompanied by volumetric contractive/dilative responses. Basic characteristics and predictive capability of the proposed model, as well as the accuracy of the developed numerical scheme, are verified through several numerical examples including monotonic and cyclic loadings. [ABSTRACT FROM AUTHOR]

• Chloroplast development activates the expression of ascorbate biosynthesis-associated genes in roots exposed to light. • The chloroplast-dependent activation is suppressed by a photosynthetic inhibitor. • A null mutation in the LONG HYPOCOTYL 5 (HY5) gene almost completely inhibited root greening as well as the VTC2 expression. Transcriptional activation of ascorbate biosynthesis-associated genes under illumination is one of the important steps in ascorbate pool size regulation in photosynthetic tissues. Several biological processes within chloroplasts such as photosynthesis are required for this activation, suggesting functional chloroplasts to play a key role. We herein found that when grown on agar plate, ascorbate content in Arabidopsis non-photosynthetic tissues, roots, are unexpectedly almost comparable to that in shoots. The high accumulation of ascorbate was particularly observed in root regions closer to the root-hypocotyl junction, in which chloroplast development occurred because of a direct exposure to light. When chloroplast development in roots were further stimulated by shoot removal, the expression of biosynthetic genes, especially VTC2 gene that encodes GDP- l -galactose phosphorylase, was activated, resulting in an increase in ascorbate pool size. These positive effects were canceled when the roots were treated with a photosynthetic inhibitor. A null mutation in the LONG HYPOCOTYL 5 (HY5) gene almost completely inhibited root greening as well as the VTC2 expression. Overall, these findings show that chloroplast development can trigger the expression of ascorbate biosynthesis-associated genes not only in leaves but also in roots. [ABSTRACT FROM AUTHOR]

This paper presents the results from a set of experiments designed to ultrasonically measure the near surface stresses distributed within a dissimilar metal welded plate. A scanning acoustic microscope (SAM), with a tone-burst ultrasonic wave frequency of 200 MHz, was used for the measurement of near surface stresses in the dissimilar welded plate between 304 stainless steel and low carbon steel. For quantitative data acquisition such as leaky surface acoustic wave (leaky SAW) velocity measurement, a point focus acoustic lens of frequency 200 MHz was used and the leaky SAW velocities within the specimen were precisely measured. The distributions of the surface acoustic wave velocities change according to the near-surface stresses within the joint. A three dimensional (3D) finite element simulation was carried out to predict numerically the stress distributions and compare with the experimental results. The experiment and FE simulation results for the dissimilar welded plate showed good agreement. This research demonstrates that a combination of FE simulation and ultrasonic stress measurements using SAW velocity distributions appear promising for determining welding residual stresses in dissimilar material joints. [ABSTRACT FROM AUTHOR]

Obg-like ATPase 1 (OLA1) is a binding protein of Breast cancer gene 1 (BRCA1), germline pathogenic variants of which cause hereditary breast cancer. Cancer-associated variants of BRCA1 and OLA1 are deficient in the regulation of centrosome number. Although OLA1 might function as a tumor suppressor, the relevance of OLA1 deficiency to carcinogenesis is unclear. Here, we generated Ola1 knockout mice. Aged female Ola1 +/− mice developed lymphoproliferative diseases, including malignant lymphoma. The lymphoma tissues had low expression of Ola1 and an increase in the number of cells with centrosome amplification. Interestingly, the proportion of cells with centrosome amplification in normal spleen from Ola1 +/− mice was higher in male mice than in female mice. In human cells, estrogen stimulation attenuated centrosome amplification induced by OLA1 knockdown. Previous reports indicate that prominent centrosome amplification causes cell death but does not promote tumorigenesis. Thus, in the current study, the mild centrosome amplification observed under estrogen stimulation in Ola1 +/− female mice is likely more tumorigenic than the prominent centrosome amplification observed in Ola1 +/− male mice. Our findings provide a possible sex-dependent mechanism of the tumor suppressor function of OLA1. [Display omitted] • Ola1 heterozygous knockout promotes tumorigenesis of lymphoma in aged female mice. • Decreased expression of Ola1 correlates with centrosome amplification in tumors. • Estrogen stimulation suppresses the centrosome amplification induced by Ola1 deficiency. [ABSTRACT FROM AUTHOR]

E-Defense shake table experiments on a 7.5 m tall, 1.8 m by 1.8 m square bridge column using polypropylene fiber-reinforced cement composites (PFRC) at the plastic hinge region and part of the footing is presented. The column was excited using 80% of the original intensity of the near-field ground motion recorded at the JR Takatori Station during the 1995 Kobe, Japan earthquake. Use of PFRC mitigated cover and core concrete damage, local buckling of longitudinal bars, and deformation of ties even after six times of repeated excitation. The damage sustained was much less than the damage of regular reinforced concrete columns. [ABSTRACT FROM PUBLISHER]

This article presents the seismic performance of scaled bridge columns using polypropylene fiber reinforced cement composite (PFRC), steel fiber reinforced concrete (SFRC), and reinforced concrete (RC) in combination with high strength longitudinal bars. The columns were subjected to combined axial and bilateral cyclic loading. Use of PFRC and SFRC mitigated damage of cover and core concrete, local buckling of longitudinal bars and strains induced in ties compared with the RC column. Damage mitigation and lateral confinement effect was superior in PFRC than SFRC. While PFRC and SFRC reduced the damage, their flexural strength and ductility capacity were similar with the RC column. [ABSTRACT FROM AUTHOR]

To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1* 6/* 28 and SLCO1B1* 15/* 15 genotypes. A 66-year-old Japanese male diagnosed with left pharyngeal carcinoma (T2N2bM0, stage IVA) was treated with irinotecan (70 mg/m2) on days 1, 8 and 15 in combination with docetaxel (60 mg/m2) on day 1 of a 28-day cycle. After the first cycle, he suffered marked toxicities, including grade 4 diarrhea and febrile grade 4 neutropenia. Plasma concentrations of irinotecan, SN-38 and SN-38G were measured, and extensive accumulation of SN-38 was observed. Genotyping of UGT1A1 and OATP1B1 proteins showed UGT1A1* 6/* 28 and SLCO1B1* 15/* 15, respectively, which are known to lead to extremely low glucuronidation and transport activities of substrate drugs. The severe toxicities in this patient are attributable to the extensive accumulation of SN-38, which may result from a synergistic or additive effect of low metabolic ( UGT1A1* 6/* 28) and transport ( SLCO1B1* 15/* 15) capabilities. [ABSTRACT FROM AUTHOR]

To elucidate the specific function of m-calpain in the metabolism of aggrecan in human articular cartilage, the prevalence and localization of a large glycosaminoglycan-bearing aggrecan product generated by m-calpain in human osteoarthritis (OA) cartilage were investigated. Extracts of human OA articular cartilage were analysed by immunostaining using new polyclonal anti-VPGVA antiserum that detects the COOH terminal neoepitope IVTQVVPGVA709 generated by m-calpain-related cleavage within the keratan sulphate rich region of human aggrecan. Immunoblotting analyses of aggrecan populations in guanidine hydrochloride-extracts showed that OA cartilages contained anti-VPGVA positive aggrecan products with the COOH terminal neoepitope … VPGVA709, resulting from truncation between the Ala709–Ala710 m-calpain-related cleavage site. This aggrecan product consisted of two NH2 terminal globular domain (G1 and G2) and KS side chains. Immunohistochemical staining showed that anti-VPGVA positive staining was localized within chondrocytes and spread to the surrounding interterritorial matrix. Confocal microscopic analysis showed subcellular colocalization of anti-VPGVA and anti m-calpain. These results indicate that the aggrecan product with the COOH terminal neoepitope VPGVA709 is synthesized regularly by intracellular processing in chondrocytes, and is present abundantly as a limited form of aggrecan. M-calpain is the major candidate of the proteinase to generate this aggrecan product during the intracellular aggrecan processing. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Direct revascularization through a superficial temporal artery-middle cerebral artery (STA-MCA) bypass is often performed to prevent ischemic or hemorrhagic attack in patients with moyamoya disease. This is the first reported case of aneurysm formation and rupture due to an STA-MCA bypass in a patient with moyamoya disease. Case Description: A 52-year-old man who had undergone bilateral STA-MCA bypass for caudate hemorrhage due to moyamoya disease 20 years previously suffered from sudden-onset unconsciousness. Computed tomography revealed a massive intracerebral hematoma (ICH) in the left frontoparietal region. Angiography showed good patency of the anastomoses and stage IV moyamoya disease. However, no other abnormality was found. Emergency evacuation of the hematoma was performed. The patient''s postoperative course was uneventful, but consciousness disturbance of sudden onset occurred 1 month later. Computed tomography showed a hematoma in the lateral ventricle and acute hydrocephalus. Repeat angiography revealed an aneurysm on the left side of the anastomosis. Bilateral ventricle drainage tubes were inserted, and the aneurysm was clipped. A ventriculoperitoneal shunt was later performed. Conclusion: In patients with moyamoya disease who have undergone extracranial-intracranial bypass surgery, progressive hemodynamic stress may cause the formation of de novo aneurysms after a postoperative period of several decades. Imaging examinations should therefore be performed periodically for follow-up, and a de novo aneurysm should be suspected in a patient who has an unusual ICH. [Copyright &y& Elsevier]

The deformation and fracture mechanism in 7075 aluminum alloy is discussed based on a field theoretical approach. A pair of peak-aged and overaged plate specimens are prepared under the respective precipitation conditions, and their plastic deformation behaviors are visualized with two-dimensional electronic speckle pattern interferometry (ESPI). The in-plane velocity field caused by monotonic tensile loading is monitored continuously via the contour analysis method of ESPI. In the plastic regime, the peak-aged specimen exhibits a macroscopically uniform deformation behavior, while the annealed specimen exhibits non-uniform deformation characterized by a localized shear band. The occurrence of the shear band is explained by the transition of the material's elastic resistive mechanism from the longitudinal force dominant to shear force dominant mode. The shear force is interpreted as the frictional force that drives mobile dislocations along the shear band. The dynamic behavior of the shear band is explained as representing the motion of a solitary wave. The observed decrease in the solitary wave's velocity is accounted for by the change in the acoustic impedance with the advancement of plastic deformation. [ABSTRACT FROM AUTHOR]

Measured force-displacement sensing data are analyzed to create nonlinear hysteretic models for elastic sliding bearings and steel dampers. These data were collected during full-scale experimental tests of a base-isolated structure at Japan's National Research Institute for Earth Science and Disaster Resilience (NIED) "E-Defense" Hyogo Earthquake Engineering Research Center in 2013 that employed historical and synthetic earthquake inputs. Several models are explored for each isolation-layer device, including Coulomb friction models for the elastic sliding bearings and Bouc-Wen hysteresis models for both devices. Parameters for each device model are estimated via constrained nonlinear optimization to minimize model prediction error using testing data. The resulting models are applied to data from other seismic tests to evaluate the models' ability to provide accurate force predictions. The model for the steel dampers demonstrates the capacity to be generalized across seismic excitations and devices, whereas the model for the elastic sliding bearing reproduces well its behavior during other seismic excitations but is limited to the device to which it was calibrated. The residual error between the model predictions and measurements does not contribute a significant degree of variance in the model parameter estimates. [ABSTRACT FROM AUTHOR]

Summary: Full‐scale dynamic testing and earthquake engineering experiments are often costly, yet they are vital for advancing the understanding of the complex interactions between seismic protective systems and structural responses. E‐Defense (a part of the Japan's National Research Institute for Earth Science and Disaster Resilience) constructed and tested a four‐story reinforced‐concrete base‐isolated building to study, among other things, how different anti‐seismic devices in the isolation layer of a building improve its response. This structure was subjected in August 2013 to a series of tests, including random ground motions and simulated earthquakes. Analyzing the acceleration responses from these random excitations forms the first step in identifying the dynamic characteristics of this test structure. The advanced numerical algorithm for subspace state‐space system identification (N4SID), from the family of subspace identification methods, is used to estimate the nominal modal parameters of this structure for both input–output and output‐only models. These models are then evaluated for their generalizability by using them to predict the response of the structure to both random excitations and seismic inputs. Additional identification is performed using responses recorded during simulated earthquakes, and the recovered modal parameters are compared against the nominal parameters to analyze how the building's isolation system impacts its response. The results indicate that the interaction between seismic excitation and the base‐isolation layer has both local and global structural effects. Locally, the modes most directly associated with isolation layer displacements experience, as expected, significant decreases in frequency and increases in damping; globally, the modes with more substantial displacements across the superstructure also experience decreases in frequency and increases in damping but at a greatly reduced scale. Further, even in the presence of seismic forces large enough to induce nonlinear restoring forces in the isolation layer, the relative changes in identified modal parameters for the superstructure associated modes remained modest. [ABSTRACT FROM AUTHOR]

Large-scale seismic structural tests are crucial to validating both structural design methodologies and the effectiveness of seismic isolation devices. However, considering the significant costs of such tests, it is essential to leverage data from completed tests by taking advantage of numerical models of the tested structures, updated using data collected from the experiments, to complete additional studies that may be difficult, unsafe or impossible to test physically. However, updating complex numerical models poses its own challenges. The first contribution of this paper is to develop a multi-stage model updating method suitable for high-order models of base-isolated structures, which is motivated and evaluated through modeling and model updating of a full-scale four-story base-isolated reinforced-concrete frame building that was tested in 2013 at the NIED E-Defense laboratory in Japan. In most studies involving model updating, all to-be-updated parameters are typically updated simultaneously; however, given the observation that the superstructure in this study predominantly moves as a rigid body in low-frequency modes and the isolation layer plays a minor role in all other modes, this study proposes updating parameters in stages: first, the linear superstructure parameters are updated so that its natural frequencies and mode shapes match those identified via a subspace system identification of the experimental building responses to low-level random excitations; then, the isolation-layer device linear parameters are updated so that the natural frequencies, damping ratios and mode shapes of the three isolation modes match. These two stages break a large-scale linear model updating problem into two smaller problems, thereby reducing the search space for the to-be-updated parameters, which generally reduces computational costs regardless of what optimization algorithm is adopted. Due to the limited instrumentation, the identified modes constitute only a subset of all modes; to match each identified mode with a FEM mode, the second contribution is a procedure proposed to compare each identified mode with a candidate set of FEM modes and to select the best match. Further, nonlinear isolation-layer device models are proposed, updated and validated with experimental data. Finally, combining the isolation-layer devices' nonlinear models with the updated superstructure linear FEM, the final result is a data-calibrated nonlinear numerical model that will be used for further studies of controllable damping and validation of new design methodologies, and is being made available for use by the research community, alleviating the dearth of experimentally-calibrated numerical models of full-scale base-isolated buildings with lateral–torsional coupling effects. • Developed two-stage modal linear model updating method for base-isolated buildings. • Evaluated with full-scale E-Defense shake-table experimental measured responses. • Proposed a new algorithm to match model modes to those from system identification. • Nonlinear isolation-layer device models are calibrated from experimental data. • Combined partially linear model predicts well the structure time–history responses. [ABSTRACT FROM AUTHOR]

A novel partitioning collection device comprising a glass cartridge packed with poly(dimethylsiloxane)-coated macroporous silica particles was developed for the precise quantification of polycyclic aromatic hydrocarbons in air. The analyte collection and elution performances achieved using different amounts of poly(dimethylsiloxane) coating were quantitatively evaluated. The sample retention power increased with increasing the coating, and more than 250 L of air could be collected without analyte breakthrough at a sampling temperature of 35°C. During the air collection, the moisture in the air was not retained on the particles due to the hydrophobic surface of the sorbent. A complete and rapid elution of the collected analytes from the device was accomplished by the passage of only 10 mL of acetone with ultrasonication for 1 min. The proposed method was successfully applied for the determination of airborne polycyclic aromatic hydrocarbons in tunnel air. [ABSTRACT FROM AUTHOR]

A novel sampling device based on the partition of target analytes to the extraction medium was developed for the determination of sesquiterpenes in air samples. The extraction medium was prepared by the chemical derivatization of a specially prepared macroporous silica, with a specific surface area of 2.0 m2/g. Taking advantage of the sample extraction, which was mainly based on the partition of sesquiterpenes between air and a C18-bonded phase, the extracted analytes were rapidly and quantitatively desorbed just by passing a small amount of desorption solvent for subsequent analysis by gas chromatography with mass spectrometry. Several experimental conditions, such as the sampling volume and temperature, were systematically evaluated. Under optimized conditions, desorption of the extracted analytes was completed within 1 min with a desorption efficiency of more than 99.9%, achieved using 5 mL of acetone for all the evaluated sesquiterpenes. The applicability of the developed device was confirmed by the determination of several sesquiterpenes from coniferous trees. Although further improvements of the device are required for collecting large volumes or high-temperature air samples, the potential of the developed sampling device was confirmed by determining traces of semivolatile organic compounds in air samples. [ABSTRACT FROM AUTHOR]

The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype-matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally 97.5 µg) and then a TD (100 mg) of celiprolol, with and without grapefruit juice. The mean AUC0-24 of celiprolol was lower in SLCO2B1*3/*3 individuals (775 ng·h/mL) than in *1/*3 (1097 ng·h/mL) and *1/*1 (1547 ng·h/mL) individuals following the TD, and this was confirmed in population pharmacokinetic analysis with statistical significances; however, SLCO2B1 genotype-dependent differences disappeared following the MD. Dose-normalized AUC of celiprolol at the MD was much lower than that at the TD, explained by the saturation of the efflux transporter. Thus, the effect of SLCO2B1 polymorphism on the AUC of celiprolol clearly observed only at the TD may be due to the saturation of the efflux transport systems. [ABSTRACT FROM PUBLISHER]

In this study, we evaluated (a) the contribution of SLCO1B3 and UGT1A polymorphisms to the pharmacokinetics of telmisartan in two forms, a microdose (MD) and a therapeutic dose (TD); (b) linkage disequilibrium (LD) between UGT1A1 and UGT1A3; and (c) linearity in the pharmacokinetics of telmisartan between the two forms.Telmisartan was orally administered at MD condition (100 μg), and then at TD condition (80 mg) to 33 healthy volunteers whose genotypes were prescreened by DMET Plus. Plasma concentrations of telmisartan and its glucuronide were measured by LC-MS/MS, and population pharmacokinetic analysis was performed.No obvious effect of SLCO1B3 polymorphisms (334T>G, 699G>A, and rs11045585) on the pharmacokinetics of telmisartan was observed. The strong LD between UGT1A1∗6 and UGT1A3∗4a, and between UGT1A1∗28 and UGT1A3∗2a were observed. After both MD and TD administration, the mean area under the curve0-24 (±standard deviation) of telmisartan was significantly lower and higher in individuals with the UGT1A3∗2a (TD, 1701±970 ng hr/ml; MD, 978±537 pg hr/ml) and ∗4a variants (TD, 5340±1168; MD, 3145±1093), respectively, compared with those in individuals with UGT1A3∗1/∗1 (TD, 2969±1456; MD, 1669±726). These results were quantitatively confirmed by population pharmacokinetic analysis. Nonlinearity of the dose-exposure relationship was observed between the MD and TD.The haplotypes of UGT1A3 significantly influenced pharmacokinetics of telmisartan and a strong LD between UGT1A1 genotype and UGT1A3 haplotype was observed. These findings are potentially of pharmacological and toxicological importance to the development and clinical use of drugs. [ABSTRACT FROM AUTHOR]

Licorice ingestion, as well as mutations in the HSD11B2 gene, inhibits 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) enzyme activity, causing the syndrome of apparent mineral corticoid excess (AME). However, the combined effect of licorice ingestion and an HSD11B2 mutation has never been reported, until now. In this study, we demonstrated that licorice ingestion can produce overt hypertension in an individual without medical history of hypertension who is heterozygous for wild-type and mutant HSD11B2 genes. Our patient was a 51-year-old female with serious hypertension who had been taking herbal medicine containing licorice for more than one year. She was clinically diagnosed as having licorice intoxication, because she did not present with hypertension after ceasing the herbal medicine. Molecular analysis showed that she carried a missense mutation, c.40C>T, in HSD11B2. In conclusion, licorice ingestion is an environmental risk factor for hypertension or AME state in patients with a mutation in HSD11B2. Carrying a mutation in HSD11B2 is, conversely, a genetic risk factor for licorice-induced hypertension or AME state. Herbal medicine containing licorice may, therefore, be contraindicated in patients with an HSD11B2 mutation. [ABSTRACT FROM AUTHOR]

Abstract: Authors investigated the effect of ultrasonic vibration on the solidification microstructure and mechanical properties of the weld metal of ferritic stainless steel by introducing directly ultrasonic vibration into the weld molten pool using ultrasonically vibrating filler metal. The main results obtained in this study are as follow. The ultrasonically vibrating filler metal could successfully transmit ultrasonic vibration to the weld molten pool. Ultrasonic vibration encouraged equiaxed grains to form in the central region of the weld metal. The more equiaxed grains formed due to ultrasonic vibration, the higher the welding speed was. The tensile strength of the weld with ultrasonic vibration was larger than that without vibration. The tensile fracture elongation of the weld with ultrasonic vibration remarkably increased compared to that without vibration. When the distance between an electrode tip and the filler metal was too short, the weld bead was less stably formed. [Copyright &y& Elsevier]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Cranberry juice has a significant inhibitory effect on CYP2C9 activity in vitro, whereas it shows a minimal effect on the pharmacokinetics and pharmacodynamics of warfarin, a CYP2C9 substrate in vivo. • Information regarding the interaction between cranberry juice and other medications metabolized by CYP2C9 is limited. WHAT THIS STUDY ADDS • Cranberry juice suppressed the metabolism of diclofenac, another CYP2C9 substrate, by human liver microsomes. • Pharmacokinetic parameters of diclofenac were not altered by cranberry juice consumption in human subjects. AIM To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9. METHODS The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics. RESULTS Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects. CONCLUSIONS Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro, it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations. [ABSTRACT FROM AUTHOR]

Introduction: To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes. Case Report: A 66-year-old Japanese male diagnosed with left pharyngeal carcinoma (T2N2bM0, stage IVA) was treated with irinotecan (70 mg/m(2)) on days 1, 8 and 15 in combination with docetaxel (60 mg/m(2)) on day 1 of a 28-day cycle. After the first cycle, he suffered marked toxicities, including grade 4 diarrhea and febrile grade 4 neutropenia. Plasma concentrations of irinotecan, SN-38 and SN-38G were measured, and extensive accumulation of SN-38 was observed. Genotyping of UGT1A1 and OATP1B1 proteins showed UGT1A1*6/*28 and SLCO1B1*15/*15, respectively, which are known to lead to extremely low glucuronidation and transport activities of substrate drugs. Conclusion: The severe toxicities in this patient are attributable to the extensive accumulation of SN-38, which may result from a synergistic or additive effect of low metabolic (UGT1A1*6/*28) and transport (SLCO1B1*15/*15) capabilities. [ABSTRACT FROM AUTHOR]