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Creep by solvent squeeze of cylindrical κ-carrageenan gels is investigated. A phenomenological model to describe the creep and the solvent squeeze of polymer gels is also presented. Under compression, the creep of gels proceeds at a constant diameter except for the initial stage of creep. The change in height of the gels is well reproduced by the sum of three exponential terms, each of which is specified by the combination of displacement and retardation time. The displacement for the second mode, which corresponds to the second longest retardation time, becomes largest for all gel specimens. Three retardation times are commonly proportional to the square of initial diameter of gel specimens. Based on the proposed model, the spring constant in the second mode becomes smallest and the permeability corresponding to the third mode becomes larger than those in the other two modes.

Background Patients with thrombocytopenia associated with chronic liver disease (CLD) are at greater risk of bleeding during invasive procedures. This study characterized the pharmacokinetic/pharmacodynamic (PK/PD) profile of lusutrombopag, a novel thrombopoietin-receptor agonist, using modelling and simulation, and evaluated the appropriate dose regimen for treatment of thrombocytopenia in CLD patients undergoing invasive procedures. Methods A population PK/PD model was developed using plasma lusutrombopag concentrations from 78 healthy subjects and 349 CLD patients, as well as platelet counts from 347 of these 349 patients. Covariates were explored from subject characteristics. Monte-Carlo simulations were performed to assess a dose response for efficacy (platelet counts ≥ 50,000/μL) and a risk for platelet overshooting (platelet counts > 200,000/μL). Results Visual predictive checks indicated the developed models described the PK/PD profile of lusutrombopag well. In the simulations, without stopping criteria, lusutrombopag 3 mg once daily for 7 days before scheduled invasive procedures provided effective platelet response (85.2% probability for efficacy). The probability of platelet overshooting was 1.2%, indicating that platelet monitoring is not necessary. Although body weight was an influential covariate on the pharmacokinetics of lusutrombopag, individually estimated peak platelet counts overlapped among the body weight groups, suggesting no clinically significant effect on body weight. Conclusion The modelling and simulation support lusutrombopag 3 mg once daily for 7 days without platelet monitoring. Electronic supplementary material The online version of this article (10.1007/s40262-019-00770-4) contains supplementary material, which is available to authorized users.

This study extends Hirano and Yanagawa (Rev Econ Stud 84(1):406–443, 2017) to an asymmetric two-country model and examines bubbles effects on each country’s long-run economic growth rate. This study also provides numerical examples with respect to the relationship between each country’s growth rate and their financial frictions in the balanced growth equilibria with bubbles and without bubbles. It shows that foreign bubbles have positive and negative effects on both countries’ growth rates, and which effect dominates depends on the level of financial development in both countries. In this study, the positive effect of bubbles tends to dominate when the total level of financial frictions in both countries is relatively low. When the total effect of bubbles on the growth rate is positive, the burst of foreign bubbles leads to a decrease in the growth rate in both countries. This implies that there is a positive correlation between foreign bubbles and the domestic as well as the foreign country’s growth rate.

The sol-gel transition entropy is estimated by using a modified Clapeyron-type equation for κ-carrageenan hydrogel systems under load. The effect of alkali metal salts on the sol-gel transition behavior is also investigated. The transition temperature decreases with increasing compressional stress, while the transition entropy remains unchanged. Both the transition entropy and the transition temperature at the zero stress limit vary almost in accordance with the Hofmeister series, but the inversion occurs for RbCl and CsCl. For the gels examined, a positive correlation exists between the transition entropy and the transition temperature at the zero stress limit.

The author noticed that the published paper contained error. Unfortunately, Table 2 was incorrectly presented. Given in this paper is the correct table.

Second-generation antisense oligonucleotides (ASOs) demonstrate excellent biological stability and in vitro/in vivo potency, and thus are considered to be attractive candidates for drugs to treat various diseases. A pharmacokinetic-pharmacodynamic (PK-PD) model of ASOs is desired for the design of appropriate PK and pharmacological studies. The objective of this study was to develop a PK-PD model to accurately simulate hepatic ASO concentration and its efficacy from plasma ASO concentration. After single subcutaneous administration of an ASO targeting hepatic apolipoprotein B (Apo-B) mRNA to mice, the ASO was absorbed rapidly and showed biphasic decline with time from the plasma and liver (t1/2: 1-3 and 81-183 h, Tmax: 0.25-0.50 and 4-8 h). After administration, hepatic Apo-B mRNA and plasma total cholesterol began decreasing at 4-8 and 8-24 h, and their Tmax values were observed at 24-72 and 72 h. To develop the PK-PD model based on the mechanisms of ASOs, we described the plasma and hepatic ASO concentration with linear two-compartment models. In addition, we inserted two indirect response models for mRNA and plasma total cholesterol. Model predictions from plasma ASO concentration gave excellent fits to the observed values of hepatic ASO concentration, Apo-B mRNA and plasma total cholesterol after single or multiple subcutaneous administrations. Our PK-PD model could accurately predict hepatic ASO concentrations and their efficacies from plasma ASO concentrations. This PK-PD model could be a useful tool for suggesting PK and pharmacological study protocols for various liver-targeted second-generation ASOs.

We examined optical cavity effects on the 2-photon absorption efficiency of a dye (Rohdamine B; RhB) doped in polymer microspheres (ion-exchanging resin and poly(methyl methacrylate) (PMMA)). When 1064 nm pulsed-laser light was irradiated on single polymer microspheres doped with RhB under an optical microscope, we clearly observed dye fluorescence from individual microspheres, although the dye was transparent at 1064 nm. We confirmed that the fluorescence intensity was proportional to the square of the laser power for excitation. In contrast, such fluorescence was not observed from RhB doped in a PMMA film, in which the enhancement of a light electric field by an optical cavity effect was never expected. Theoretical calculations indicated that the microsphere possessed several peak values of the quality factor (Q = 10^[2] - 10^[5]) at around certain particle diameters under 1064 nm irradiation. This means that the electromagnetic field of incident light is enhanced through light confinement in a microsphere. Based on these results, we conclude that the 2-photon absorption probability of RhB would be considerably enhanced by the optical cavity effects of the microsphere.

Optical fibres have proved to be an important medium for manipulating and generating light in applications including soliton transmission1, light amplification2, all-optical switching3 and supercontinuum generation4. In the quantum regime, fibres may prove useful for ultralow-power all-optical signal processing5 and quantum information processing6. Here, we demonstrate the first experimental observation of optical nonlinearity at the single-photon level in an optical fibre. Taking advantage of the large nonlinearity and managed dispersion of photonic crystal fibres7,8, we report very small (1 × 10−7 to ∼1 × 10−8 rad) conditional phase shifts induced by weak coherent pulses that contain one or less than one photon per pulse on average. We discuss the feasibility of quantum information processing using optical fibres, taking into account the observed Kerr nonlinearity, accompanied by ultrafast response time and low induced loss. The tiny phase changes introduced by nonlinear optics performed at the single-photon level is reported in a photonic crystal fibre with carefully designed nonlinear and dispersion properties. The approach may prove useful in future quantum information processing schemes.

We present two-photon diffraction and interference experiments utilizing parametric down-converted photon pairs (biphotons) and a transmission grating. The biphoton exhibits a diffraction-interference pattern equivalent to an effective single particle with half wavelength of the constituent photons.

We investigated the process of the hole inlet closure in surface-diffusion-driven transformation of arrays of high-aspect-ratio holes on Si(001) substrates. The inlet gradually shrinks while keeping the circular shape because of lateral bulging of the inlet surface. We observed complicated top view morphologies reflecting the four-fold symmetry of the Si(001) surface on the inlet surface. Large {111} and {113} facets are formed in the four equivalent azimuths of the [110], while corrugated patterns arise in the four equivalent azimuths of the [100]. Atomic force microscopy observations reveal that the corrugated pattern is composed of three types of small facets, namely, {110} and two {113} in relation of the mirror symmetry. The corrugated pattern formation is due to the geometrical restriction that there is no stable facet between (001) and (010) in the [010] azimuth. The observed morphological evolution is interpreted as surface-diffusion-driven transformation under constraint of the anisotropic surface energy of Si.

High-temperature silicon dioxide chemical vapor deposition (HTOCVD), using SiH2Cl2 and N2O, can realize dense and conformal oxide film, not only on large size silicon wafers, but even inside of microscopic silicon trenches, at high-temperature around 800°C.In this work, we investigated the kinetics of HTOCVD using a commercial scale low pressure (LP) CVD reactor, focusing on the correlation between deposition rate and surface-to-volume ratio (S/V ratio), which is a specific surface area of substrate wafer divided by the space volume between two adjacent wafers. We also investigated the deposition rate profile on wafers, and along the axial direction of the reactor near the region where one, two or three substrate wafers are extracted from the quartz holder. The deposition rate profiles on wafer characteristically change from skillet-like to pancake-like, according to the increase of wafer spacing. The influence on the deposition rate of wafer spacing spreads to ranges not only downstream, but also upstream in the gas flow. These experimental results strongly suggest that in the HTOCVD gas-phase reactions through intermediate states of active species contribute to deposition reaction as well as direct deposition reaction of source gases on Si surface.

We have developed an atomic force microscopy (AFM) observation technique with which Si trench sidewall surface can be scanned with the tip of cantilever to investigate its nano-scale morphologies. By developing a new technique of cleaving the substrate at the center of a micron-sized trench along its longitudinal direction [011], the sidewall nano-scale morphology of the trench could be observed with the AFM technique. By comparing of cross sections of the images, we also investigated the difference between Si and carbon nanotube (CNT) tips for the AFM observations. According to the results, the CNT tip proved to show a superior signal-to-noise (S/N) ratio compared with the Si tip. The CNT tip enables us to observe the step patterns of the sidewalls of micron-sized trench structures in the various phases of hydrogen annealing.

We have examined how the morphology of the trench sidewall evolves in the early phase of hydrogen annealing under the two conditions of hydrogen pressures. A distinguished result was obtained concerning the sidewall surface morphology after 30 s annealing at 1000 °C under 760 Torr hydrogen ambient. The evanescence of chemical Si dioxide formed by RCA cleaning process was clearly observed to initiate in various places on the surface. And in the area without chemical oxide, the appearance of atomic steps was also observed. In contrast under 40 Torr hydrogen ambient, the chemical oxide was completely removed even after 30 s annealing. Our observation shows that not only the rate of trench shape transformation but also the rate of removal of oxide films decreases with increasing hydrogen pressure.

Thickness uniformities of poly-crystalline silicon thin films, deposited by a commercial LPCVD reactor, were investigated through a phenomenological and elementary reaction analysis. To understand the deposition rate and its profile in radius direction of ø 6”h silicon wafer, concentration distributions of film precursors were examined by solving basic diffusion equations of film precursors in the CVD system. The experimental thickness distribution can be simulated very well with the solution by optimizing η, the sticking probabilities of the precursors. While most of the silicon deposition was made by source precursor (mono-silane, SiH4), two kinds of intermediate species with sticking probabilities of 5X10-2 and 7X10-4 were found to contribute the deposition. Subsequently, elementary chemical reaction analysis of poly-crystalline silicon CVD process was performed using ChemKinTM and two chemical species, SiH2 and Si2H6, were identified as the possible candidates for the intermediate species.

Nanolithography has been studied by using electron beam technology. Ten-nm linewidth PMMA resist patterns have been demonstrated by 50 kV scanning electron beam. The self-developing properties of a AlF3 doped LiF inorganic resist under a scanning electron beam irradiation with energy of 20–50 keV have been studied for sub-10 nm lithography. By optimizing the inorganic resist film quality, 5 nm linewidth patterns with 60 nm periodicity were directly delineated under a 30 keV electron beam. Another approach for nanolithography using electron beam holography has been proposed. Line and dot patterns with 100 nm periodicity were exposed on PMMA resist by electron beam holography with thermal field emitter gun and an electron biprism. Subsequent atomic force microscope observation has confirmed that both patterns are successfully fabricated. This technique allows us to produce nanoscale periodic patterns simultaneously. The selective atomic desorption of Cl atoms adsorbed on a Si (111) 7×7 surface has been studied by field evaporation using a scanning tunneling microscope (STM). The STM tip is placed on the adsorbed Cl on the surface, and pulse voltage was applied. This results in selective atomic desorption of Cl.