Search

Background: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. Materials and methods: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. Results: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. Conclusions: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

The use of molecular beacons is a versatile method to detect RNAs. Typically, a single-stranded region of RNA is selected as a target sequence for molecular beacons. Therefore, the detection of highly structured short RNAs, such as tRNAs, seems to be difficult. In this study, as an example of highly structured target RNA, we used human tRNALys3, which is known to have functions in protein synthesis and the reverse transcription of human immunodeficiency virus (HIV)-1. No long single-stranded region more than 8 nt is present in this tRNA, which is much shorter than the standard target length of molecular beacons (∼20 nt). This study showed that sensitive detection of highly structured RNAs using molecular beacons was much more difficult than that of unstructured or less structured RNAs. However, efficient detection of the tRNALys3 was achieved by selecting the best target region, i.e., the region around the D arm, probably due to the ease of unfolding of this arm. Accordingly, our findings suggested that molecular beacons may have applications in the detection of highly structured RNAs related to various biological functions and diseases.

Experimental feeds containing 0, 500, 1000, 1500 or 2000 ppb of lolitrem B derived from perennial ryegrass straw were fed to 9 month-old Japanese Black steers (average liveweight 180 kg) to determine their threshold level of lolitrem B. Steers received feeds containing 1000, 1500 and 2000 ppb of lolitrem B showed signs of ryegrass staggers after 2 to 7 weeks of feeding. The lowest observed adverse effect level (LOAEL) of lolitrem B was approximately 24 μg/kg body weight per day. Only small amounts of lolitrem B residue were detected in muscle, liver, kidney and cerebrum. In contrast, approximately 100 ng/g of lolitrem B was detected in perirenal fat of steers with ryegrass staggers. Keywords: Lolitrem B, Japanese Black cattle, ryegrass staggers, muscle, fat

This paper is concerned with an experimental investigation on plane submerged water jets discharged into quiescent water in an open channel. Flows are visualized by using hydrogen bubbles, solid particles and dye. The results show that the jets attaching to the water surface by the Coanda effect are classified into six types according to their behavior after issuing from the nozzle, and that the self-induced vibration of the jet, which is one of six flow patterns, occurs under the condition of the reduced Froude numberFr *≒0.7∼1.0. An additional analysis of the photographs reveals that the self-induced vibration of the jet is caused by attachment of the jet to the water surface and the ensuing bifurcation of the jet at an attachment point, and that the frequency of vibration is independent of the water level.

We characterized the 3,5,3′-L-triiodothyronine (T3)- uptake system on the plasma membrane of Rana catesbeiana tadpole red blood cells (RBCs) in the presence of a variety of inhibitors and potentially competing amino acids. Saturable [125I]T3 uptake was inhibited by phloretin, monodansylcadaverine, bromosulfophthalein, sodium taurocholate and tryptophan. Saturable uptake obeyed simple Michaelis–Menten kinetics with an apparent Km of 110 nM and a Vmax of 2.5 pmol/min per 106 cells at 23 °C. These results suggested that a large proportion of T3 transported into RBCs was mediated by the aromatic amino acid transporter (System T)-linked transporter. To investigate the effect of endocrine-disrupting chemicals (EDCs) on [125I]T3 uptake, RBCs were incubated with [125I]T3 in the presence of each chemical. Among the test chemicals, di-n-butyl phthalate, n-butylbenzyl phthalate and the miticide, dicofol, were the most powerful inhibitors of [125I]T3 uptake, with an IC50 of 2.2 μM, which was one order of magnitude greater than that for T3 (IC50, 0.14 μM), and diethylstilbestrol and ethinylestradiol were modest inhibitors. Tributyltin accelerated saturable initial [125I]T3 uptake by 2-fold at 3.2 μM. When RBCs were cultured with 10 nM T3 at 25 °C for 2 days in the presence of monodansylcadaverine, ethinylestradiol, ioxynil or dicofol at the defined concentrations, these compounds inhibited significantly the induction of the thyroid hormone receptor α gene by T3. However, not all chemicals competed with T3 binding to the receptor at the same concentrations. Our results raise the possibility that the T3-uptake system on the plasma membrane of the tadpole RBCs could be a candidate target site for some EDCs and can modulate cellular T3 response.

In addition to the well-known plasma parameters of Mach number (MA) and plasma β, the other plasma parameter of the frequency ratio of the electron plasma to gyration, ωpe/Ωce (∝n/B), is emphasized as another important parameter for the plasma heating/acceleration process in the shock transition region. The process of energy conversion from the ion bulk flow into energetic electrons through field activity due to plasma instabilities cannot be described only by such macro averaged parameters as MA and β. The evolution of plasma instabilities largely depends on the background plasma properties, i.e., magnetic field B and density n, which is represented by ωpe/Ωce. Recent studies have shown that electron phase space hole generation due to the nonlinear evolution of Buneman instability between reflected ions and inflow electrons plays an important role in particle energization in the shock transition region. However, even under the same Mach number and plasma β, the formation of electron phase space holes dep...

In the shock transition region the process of electron–ion coupling under Buneman instability between inflow electrons and reflected ions is investigated. Buneman instability often evolves into a highly nonlinear state with strong wave–particle interaction like velocity phase hole (vortex) dynamics. Previous studies have shown that these electron holes contribute to the strong electron heating and acceleration. In this study, how electron holes affect the ions and interact with them is examined. Under the condition of Buneman instability dominant, the electron holes preserve their coherent large-amplitude structure for a sufficiently long period of time to modify the ion population electrostatically. Electron holes resonate with the ion population through the ion-acoustic branch, and then some of the inflow ions are rapidly decelerated and reflected by the electric field at the electron holes. As a result of gaining additional energy from the inflow ion population, the amplitude of the electric field of t...

The aim of the present study was to determine whether treatment with polymyxin B-immobilized fibre (PMX-F) haemoperfusion, teicoplanin, or both in combination is effective in patients with methicillin-resistant Staphylococcus aureus (MRSA) sepsis. Sixty patients with MRSA sepsis were randomly assigned to one of four treatments: (A) PMX-F treatment (N=15), (B) teicoplanin treatment (N=15), (C) PMX-F and teicoplanin in combination (N=20) and (D) conventional therapy (N=10). PMX-F treatment was repeated twice. Teicoplanin was administered by intravenous injection. Plasma endotoxin levels were determined by endospecy test. Plasma endotoxin levels were reduced in groups A and C (P

Electron-ion dynamics in a perpendicular magnetosonic shock wave in a high Mach number regime is studied by using the particle-in-cell simulation. It is shown that in the shock transition layer nonlinear evolution of two-stream instabilities plays an important role on the electron rapid heating and acceleration. As the shock Mach number greatly exceeds the critical Mach number, a series of large-amplitude, coherent electrostatic waves with the electron holes in phase space are excited by the two-stream instability between the reflected ions and the incident electrons in the shock transition layer. As the incident electrons are decelerated by the instability, other electrostatic waves grow in time by another two-stream instability between the incident ions and the decelerated incident electrons. The dynamic timescale of these instabilities is of the order of ω, where ωpe is the plasma frequency. The nonlinear interaction of these waves leads to the strong electron heating as well as the nonthermal high-energy electron acceleration in the shock transition layer.

Power conserving property of the propagating transverse-magnetic wave in a strongly guiding waveguide is demonstrated using the beam-propagation method with a transformed field. A step-index profile is expressed by a sigmoid function. A tilted, asymmetrical waveguide and a Y-branching waveguide with high index contrast are analyzed and discussed.

High-power and high-temperature operation of 40 mW at 100/spl deg/C has been realized in 655-nm band multiple-quantum-well (MQW) laser diodes. Both low threshold current density and low optical power density have been achieved by optimizing InGaP-InGaAlP strained MQW separate-confinement heterostructure, high doping for acceptors in p-cladding layer and adopting low-optical-loss high-reflectivity-coating at the rear facet. Fundamental-transverse-mode operation, up to 70 mW, was obtained. High-frequency and large-intensity modulation characteristics above 1 GHz were demonstrated. The relative intensity noise values were as low as -135 dB/Hz under an optical feedback with high-frequency modulation. Stable operation of 30 mW at 70/spl deg/C over 1000 h was accomplished.

660-nm-band InGaAlP Zn-diffused window structure lasers have been fabricated using highly Zn-doped GaAs layers grown by metal-organic chemical vapor deposition as a Zn diffusion source. A multiquantum-well active region was disordered by Zn diffusion, resulting in band-gap expansion and photoluminescence-wavelength shortening. In this Zn diffusion method, the Zn diffusion length from the active region into the n-cladding layer and the PL-wavelength shortening were easily controlled by controlling the Zn-dopant amount and the Zn-doped GaAs layer thickness. This method is very suitable for mass production. Window lasers fabricated by this method operate at up to 188 mW at 25/spl deg/C, and as high as 50 mW at 85/spl deg/C, and 30 mW at 95/spl deg/C with no COD. The lasers have been operating stably for more than 1200 h at 70/spl deg/C temperature and 50-mW output power. The mean time to failure was predicted as being more than 37000 h.

To investigate the independent effect of obesity in young adulthood on the risk of non-insulin-dependent diabetes mellitus (NIDDM).Retrospective cohort design.One-thousand, one hundred and five Japanese male railway employees aged 30 y or older who received a health examination from February to May 1995.Adjusted odds ratios (ORs) for subsequent NIDDM determined by the WHO criteria or a physician's diagnosis, among men who were obese at ages 20, 25, or 30 y.Men who were obese (BMIor = 25.0 kg/m2) at ages 25 or 30 y had significantly positive ORs for NIDDM after adjustment for age and maximum BMI (8.20 and 3.94, respectively). Men in the top quintile of BMI at any age also had significantly positive ORs for NIDDM (2.13, 7.92, and 3.49, at 20, 25, and 30 y, respectively). After mutual adjustment for BMI at age 20, 25 and 30 y, only obesity at age 25 y demonstrated a significantly positive OR for NIDDM in both absolute and relative models (6.98 for BMIor = 25.0 and 9.99 for the top quintile, respectively).Men who were obese (BMIor = 25.0 kg/m2 or top quintile) at age 25 y were at significantly high risk of prevalent NIDDM in subsequent years, independent of age, maximum BMI, and BMIs at age 20 and 30 y.

Summary Sodium sulfates 11–14, 29–32, 35 and 37 of various alkyl glycyrrhizin and related compounds were synthesized. In vitro anti-HIV activities of the sulfates were compared to the activities of glycyrrhizin 1 in the inhibition of replications of HTLV-III and GUN-4. The activities of the sulfates were increased 11.1, 15.2, 9.1 and 5.0 times for 11-14 , 100.0, 125.5, 83.3 and 11.6 times for 29-32 , and 11.6 and 50.0 times for 35 and 37. From the relationship between CMC values and anti-HIV activities of the sulfates, it appeared that the sulfates exhibiting more potent antiviral activities had higher micelle forming abilities. Sodium sulfates having a triterpenoid or steroid ring in the molecule showed more potent activities than those of thioglycosides which had no such ring. From the investigation of syncytium formation, we suggest that the active sulfates inhibited HIV-1 infection early in the replication cycle of the virus.

An optimum structure of 630 nm-band InGaAlP tensile-strained multiquantum-well (MQW) laser diodes for high temperature and reliable operation has been discussed. Dependences of operation characteristics on well number, well width and tensile strain, have been investigated. From these results, it has been found that introducing tensile strain into well layers reduces threshold current, but it also reduces characteristic temperature. In addition, large tensile strain over a critical condition for lattice relaxation might cause inferior operation reliability. The authors have reached the conclusion that an MQW structure with four 80 /spl Aring/ InGaP wells, having a lattice mismatch of -0.75% is optimum for high temperature and reliable operation in the 630 mm-band. >

We have been working on optically driven microrobots capable of single cell manipulation and real-time reaction force sensing in liquid. In this report, we have developed three key technologies to realize 3D manipulation, imaging and sensing of a single living cell. (1) Fluorescent microrobot for long time imaging. (2) Surface functionalization of the robot for effective capture of cells. (3) 3D manipulation and imaging system for realtime observation. These results should lead to integrated micro robotic system that can remotely manipulate living cells in liquid to study cell-cell interactions, cellular response to mechanical stimulation, and to assemble cells into 3D structures for tissue engineering.

Ultraviolet (UV) germicidal irradiation has been applied to the sterilization of agricultural products including stored grain for foodstuffs or animal feed. Although UV treatment is known to be effective for killing pathogenic moulds that contaminate the surface of grain, it remains unclear how and to what extent such irradiation is able to eliminate mycotoxins, the fungal metabolites that have adverse effects on human and animal health. We evaluated in vitro the effects of mild (intensity = 0.1 mW cm(-2) at 254 nm UV-C) and strong (24 mW cm(-2)) UV irradiation on two feed-contaminating mycotoxins, zearalenone (ZEN) and deoxynivalenol (DON). When exposed to mild irradiation, the levels of ZEN and DON (both 30 mg kg(-1) initially) were reduced as irradiation time increased, and became undetectable at 60 min. Strong UV irradiation also reduced the mycotoxin levels in the same time-dependent manner, but more rapidly. It was therefore confirmed in vitro that UV irradiation is effective at reducing the levels of ZEN and DON. The present study provides preliminary data for establishing a practical method of using UV irradiation to reduce mycotoxin contamination in grain intended for use in feed.

We discuss dissipation process in the shock transition region based on our recent numerical simulation results. We have performed self‐consistent particle‐in‐cell (PIC) simulation and found that electron kinetics plays an important role in the dissipation process as well as generation process of non‐thermal particle population. For example, our simulation indicates that the electron is energized quite rapidly and locally through nonlinear evolution of the plasma instability caused by velocity difference (drift) between the electron and the ion species. The characteristic time and spatial scales are the electron plasma oscillation and the electron inertia length, respectively. During the evolution of the plasma instability just a little drift energy is turned into large‐amplitude electrostatic waves. These waves contribute not only to the electron energization, but also to the diffusion of the ion population in the velocity space. Resultant strong heating affects on the macroscopic shock behavior, such as reduction of the shock reformation time scale.

Visualization of two-dimensional crystal growth in a monolayer of stearic acid was attempted by using a new replica technique coupled with transmission electron microscopy. A monolayer of stearic acid prepared on the surface of distilled water (pH 5.8) was deposited onto a gold-covered glass plate under a constant surface pressure controlled at 30.0 mN m −1 . Preparation and deposition of the monolayer were conducted at 21±0.5 °C. No significant film structural defects could be visualized in a replica image of the monolayer on the electron microscopic scale. When the monolayer preparation was conducted at 21±0.5 °C and the aqueous subphase temperature was lowered to 19±0.5 °C, the two-dimensional crystal growth was electron microscopically visualized.

The high-power operation of the lateral single mode 638 nm AlGaInP laser diode was demonstrated. The stable operation up to 220 mW at 55degC was realized. This is the highest power record among the narrow stripe 638-nm LDs. This LD is suitable for micro-projector.

A direct interaction of alpha beta gamma trimeric GTP binding proteins (G proteins; G0 and Gs) with nucleoside diphosphate kinase (NDP kinase) was investigated with homogeneously purified proteins. There was a progressive release of 32Pi from [gamma-32P]ATP when GDP-bound G0 was incubated together with NDP kinase. The Pi release induced by the interaction of G0 with NDP kinase was not accompanied by the dissociation of GDP bound to the alpha-subunit of G0. This was a sharp contrast to G protein-catalyzed GTP hydrolysis observed with GTP as the substrate; the dissociation of bound GDP was essentially required for the following binding of the substrate, GTP, to be hydrolyzed. A kinetic analysis displayed different properties for the substrate of NDP kinase between free GDP and G protein-bound GDP. NDP kinase-dependent phosphorylation of GDP on G0 was indeed demonstrated with adenosine 5'-(3-O-thio)triphosphate as the phosphate donor; there was a formation of guanosine 5'-(3-O-thio)triphosphate-bound G0 from the ATP analogue. Moreover, purified Gs was readily ADP-ribosylated by cholera toxin in the presence of NDP kinase, ATP, and an ADP-ribosylation factor, also suggesting that the nucleotide form on Gs was certainly GTP. These results indicate that NDP kinase can transfer the gamma-phosphate of ATP directly to GDP bound to G proteins and that this phosphorylation results in the activation of the signal-coupling proteins. A possible role of the new activation mechanism of G proteins is discussed in comparison with the previously characterized GDP-GTP exchange pathway by the agonist-receptor complex.

This paper presents a SIFT based map building and self localization method for mobile robots. First a mapping robot with trinocular vision builds the 3-D keypoint map of unknown environment with a high accuracy and then the working robot with a monocular vision localize the own position by matching the SIFT keypoints to the map. Experimental results of mapping and localization for a real indoor scene is shown.

This paper presents an overview of a decision support system for rocket launch operation from the viewpoint of distributed collaboration mechanisms. The system comprises interface agents that mediate between operators on site or support engineers in distance and various Web services that function as large-grain-size task modules for operation support. In order to orchestrate the distributed Web services over the Internet, we have adopted semantic Web services technology that enable to compose the atomic Web services in order to achieve the given goal. The interface agent for operation support is also a Web service agent that behaves that composes Web services and executes them on behalf of each user

The fault tree analysis (FTA) and the failure mode effects analysis (FMEA) are widely applied to the safety evaluation of a system, especially in the development of large-scale and mission-critical system such as nuclear power plants, aircrafts, and space rockets. The principle of FTA and FMEA is to trace comprehensively cause-effect relations among anomaly causes and undesirable effects. Their results are summarized as trees and tables for the sake of tractability in safety evaluation. The Multi-level Flow Modeling (MFM) is a functional modeling technique. It models diagrammatically a system from the viewpoint of the means-end dimension. This paper proposes a technique to automatically generate FTA trees and FMEA table from causal relations among functions and sub-goals of a system that is expressed in the MFM model of the system with the additional ontology of device anomaly. The applicability and the effects of the technique have been confirmed through the development of a fuel injection system of a launcher for a middle-size space rocket.

[1] We investigate 17 coronal mass ejection (CME) events identified by the ACE spacecraft during solar cycle 23, focusing upon the fine structures of the sheath region between the CME and its associated shock to find their dependence on the shock parameters. We observe the planar magnetic structure (PMS) downstream of a quasi-perpendicular shock when the Alfven Mach number >2.0. Here, the PMS is characterized by the magnetic fields changing directions abruptly and intermittently within a plane parallel to the shock plane. The downstream PMS does not form when a magnetic cloud with β value 0.5 and the upstream is dominated by Alfvenic fluctuations.

[1] The dynamics of the perpendicular shock front is examined under various plasma parameters by using particle-in-cell numerical simulation. As widely accepted, above the critical Mach number (∼3) the front of (quasi-)perpendicular shocks show nonstationary behavior due to the shock self-reformation. In much higher Mach number regime (MA > 20), we find that dynamics of the shock front self-reformation can be modified. Nonlinear evolution of microinstabilities in the shock transition region results turbulent profiles in a microscopic view (≤c/ωpe), while, from a macroscopic view (>several c/ωpe) because of rapid, strong thermalization in the shock transition region, the localized accumulation of the plasma due to ion dynamics is smeared out in both of the velocity phase space and real space. As a result, the shock self-reformation is realized within a reduced time and space. We can say there is a possibility that rapid, strong dissipation helps to stabilize the macroscopic shock front dynamics; the shock self-reformation still persists, though. The strong thermalization is caused by the nonlinear evolution of two-stream instability between the electron and the reflected/incident ion components and following ion-acoustic instability. We think that the modification of the shock self-reformation process observed in high Mach number regime indicates an important role of electron kinetics and heating in the macroscopic shock front behavior.

We carried out particle-in-cell simulation to investigate the mechanism for steady and unsteady shock front formation depending on Mach number (M A ) and plasma β. When even under the same M A , depending on β, the electric and magnetic field structures in the shock transition region (STR) are much different. At lower β or/and higher M A condition, the shock front tends to be unsteady and electrons play more important role in the shock dissipation process through two-stream instability.

Whistler waves are considered to play an important role in the electron dynamics for the collisionless shock formation process at interplanetary shocks (IPSs). In this report, we analyze IPS events observed by GEOTAIL on 21 February 1994 and 15 July 2000, focusing on whistler wave properties in their upstream region extending the previous work of Shimada et al. (1999). In both events, we have identified the existence of whistler mode waves in the upstream region of the IPS as well as the tendency of the intensity increase toward the shock front. At the same time we have found the detailed features differing between these events: While the intermittent but clear wave bursts were found on 21 February 1994 event, the waves were more or less continuous on 15 July 2000 event.

As a city area progresses, it becomes difficult to obtain new routes for overhead power transmission lines and to construct transmission tower. In order to utilize existing transmission line equipped with aluminum alloy conductor steel reinforced (ACSR) and increase capacity at a low cost, up-rating conductors with low-sag such as gap type heat resistance aluminum alloy conductor steel reinforced (GTACSR) are used. But considerable time and effort is required for installation. Therefore we developed the new type low sag conductors with up-rating which were superior to GTACSR on the performance (capacity, reduction effect of sag), these conductors are easier to install. Also we investigated the workability and accessories, the prospects of commercialization are good.

Genetically modified corn has been approved as an animal feed in several countries, but information about the fate of genetically modified DNA and protein in vivo is insufficient. Genetically modified corn Bt11 is developed by inserting a recombinant DNA sequence encoding insecticidal Cry1Ab protein from Bacillus thuringiensis subsp. kurstaki. We examined the presence of corn intrinsic and recombinant cry1Ab gene by PCR, and the Cry1Ab protein by immunological tests in the gastrointestinal contents of five genetically modified corn Bt11-fed and five nongenetically modified corn-fed pigs. Fragments of corn zein (242 bp), invertase (226 bp) and of ribulose-1,5-bisphosphate carboxylase/ oxygenase genes (1,028 bp) were detected in the gastrointestinal contents of both Bt11 and nongenetically modified corn-fed pigs. Fragments of recombinant cry1Ab gene (110 bp and 437 bp) were detected in the gastrointestinal contents of the Bt11-fed pigs but not in the control pigs. Neither corn intrinsic nor cry1Ab gene fragments were detected in the peripheral blood by PCR. The gastrointestinal contents were positive for Cry1Ab protein by ELISA, immunochromatography, and immunoblot; however, these methods did not work for blood and precluded conclusions about any potential absorption of the protein. These results suggest that ingested corn DNA and Cry1Ab protein were not totally degraded in the gastrointestinal tract, as shown by their presence in a form detectable by PCR or immunological tests.