Broadband Quasielastic Scattering Spectroscopy Using a Multiline Frequency Comblike Spectrum in the Hard X-Ray Region.

We developed a novel quasielastic scattering spectroscopy system that uses a multiline frequency comblike resolution function to overcome the limit on the accessible timescale imposed by the inherent single-energy resolution of conventional spectroscopy systems. The new multiline system possesses multiple resolutions and can efficiently cover a wide time range, from 100 ps to 100 ns, where x-ray-based dynamic measurement techniques are being actively developed. It enables visualization of the relaxation shape and wave-number-dependent dynamic behavior using a two-dimensional detector, as demonstrated for the natural polymer polybutadine without deuteration.

High-throughput and high-resolution powder X-ray diffractometer consisting of six sets of 2D CdTe detectors with variable sample-to-detector distance and innovative automation system.

The demand for powder X-ray diffraction analysis continues to increase in a variety of scientific fields, as the excellent beam quality of high-brightness synchrotron light sources enables the acquisition of high-quality measurement data with high intensity and angular resolution. Synchrotron powder diffraction has enabled the rapid measurement of many samples and various in situ/operando experiments in nonambient sample environments. To meet the demands for even higher throughput measurements using high-energy X-rays at SPring-8, a high-throughput and high-resolution powder diffraction system has been developed.

Quantifying bunch-mode influence on photon-counting detectors at SPring-8.

Count-loss characteristics of photon-counting 2D detectors are demonstrated for eight bunch-modes at SPring-8 through Monte Carlo simulations. As an indicator, the effective maximum count rate was introduced to signify the X-ray intensity that the detector can count with a linearity of 1% or better after applying a count-loss correction in each bunch-mode. The effective maximum count rate is revealed to vary depending on the bunch-mode and the intrinsic dead time of the detectors, ranging from 0.

Overexpression of a predicted transketolase gene and disruption of an α-1,3-glucan synthase gene in Aspergillus oryzae DGLA3 strain enhances the yield of free dihomo-γ-linolenic acid.

Free dihomo-γ-linolenic acid (DGLA), a polyunsaturated free fatty acid (FFA), can potentially be used to produce eicosanoid pharmaceuticals, such as prostaglandin E1. Previously, we constructed an Aspergillus oryzae mutant strain, named DGLA3, which produced free DGLA at an increased yield by faaA gene disruption and cooverexpression of one elongase and two desaturase genes. In this study, we achieved a further increase.

A State-of-the-Art Roadmap for Biomarker-Driven Drug Development in the Era of Personalized Therapies.

Advances in biotechnology have enabled us to assay human tissue and cells to a depth and resolution that was never possible before, redefining what we know as the "biomarker", and how we define a "disease". This comes along with the shift of focus from a "one-drug-fits-all" to a "personalized approach", placing the drug development industry in a highly dynamic landscape, having to navigate such disruptive trends. In response to this, innovative clinical trial designs have been key in realizing biomarker-driven drug development.

Model-Based Determination of Elotuzumab Pharmacokinetics in Japanese Patients With Multiple Myeloma Incorporating Time-Varying M Protein.

A population pharmacokinetic model was developed to evaluate the effects of Japanese ethnicity, prior line of therapy (0 or ≥1), time-varying M protein, and maintenance dosing regimens (10 mg/kg intravenously every 2 weeks or 20 mg/kg intravenously every 4 weeks beginning in cycle 19) on the pharmacokinetics of elotuzumab in patients with multiple myeloma treated with elotuzumab plus lenalidomide/dexamethasone. Elotuzumab pharmacokinetics were characterized by a 2-compartment model with parallel linear (nonspecific) and Michaelis-Menten elimination from the central compartment and target-mediated elimination from the peripheral compartment. Asian race on nonspecific clearance (CL) and central volume of distribution, prior line of therapy on CL, and maximum target-mediated elimination rate (V ) were statistically significant but not considered clinically relevant (magnitude < 20%).

Electric-Field-Driven Nanosecond Ferroelastic-Domain Switching Dynamics in Epitaxial Pb(Zr,Ti)O_{3} Film.

Epitaxial oxide ferroelectric films exhibit emerging phenomena arising from complex domain configurations even at pseudoequilibrium, including the creation of domain states unfavored in nature and abrupt piezoelectric coefficients around morphotropic phase boundaries. The nanometer-sized domain configurations and their domain switching dynamics under external stimuli are directly linked to the ultrafast manipulation of ferroelectric thin films; however, complex domain switching dynamics under homogeneous electric fields has not been fully explored, especially at the nanosecond timescale. This Letter reports the nanosecond dynamics of ferroelastic-domain switching from the 90° to 180° direction using time-resolved x-ray microdiffraction under homogeneous electric fields onto an epitaxial Pb(Zr_{0.

Experimentally obtained and computer-simulated X-ray non-coplanar 18-beam pinhole topographs for a silicon crystal.

Non-coplanar 18-beam X-ray pinhole topographs for a silicon crystal were computer simulated by fast Fourier transforming the X-ray rocking amplitudes that were obtained by solving the n-beam (n = 18) Ewald-Laue dynamical theory (E-L&FFT method). They were in good agreement with the experimentally obtained images captured using synchrotron X-rays. From this result and further consideration based on it, it has been clarified that the X-ray diffraction intensities when n X-ray waves are simultaneously strong in the crystal can be computed for any n by using the E-L&FFT method.

Experimentally obtained and computer-simulated X-ray asymmetric eight-beam pinhole topographs for a silicon crystal.

In this study, experimentally obtained eight-beam pinhole topographs for a silicon crystal using synchrotron X-rays were compared with computer-simulated images, and were found to be in good agreement. The experiment was performed with an asymmetric all-Laue geometry. However, the X-rays exited from both the bottom and side surfaces of the crystal.

Population Pharmacokinetic Analysis for Daclatasvir and Asunaprevir in Japanese Subjects With Chronic Hepatitis C Virus Infection.

Daclatasvir is a nonstructural protein 5A replication complex inhibitor, and asunaprevir is a nonstructural protein 3 protease inhibitor for hepatitis C virus (HCV). In 2014, the combination therapy of daclatasvir and asunaprevir received the first global approval in Japan as the first nonribavirin, all-oral therapy for HCV treatment. The population pharmacokinetics (popPK) of daclatasvir and asunaprevir were characterized by nonlinear mixed-effects modeling using 3801 and 2626 concentration data from 336 and 265 Japanese HCV subjects, respectively.

Exposure-Response (Efficacy) Analysis of Daclatasvir and Asunaprevir in Japanese Patients With Hepatitis C Virus Infection.

The treatment of hepatitis C virus (HCV) infection has been revolutionized by the development of all-oral combination regimens of direct-acting antiviral agents. The current analysis characterized the relationship between exposures of daclatasvir (DCV; tablets) and asunaprevir (ASV; capsules) and sustained virologic response (SVR) in Japanese patients who are HCV genotype (GT) 1b nonresponders to pegylated interferon (IFN) α/ribavirin or IFNβ/ribavirin, and IFN-based therapy-ineligible naive/intolerant patients receiving DCV and ASV, and provided insight into patient covariates that were most closely associated with efficacy. The relationship between the probability of achieving SVR at 12 weeks after treatment (SVR12) and average steady-state plasma concentrations estimated from population pharmacokinetic models for DCV and ASV is described using a logistic regression model with data from a phase 2 and a phase 3 study in Japanese patients infected with HCV GT 1b (N=265).

In-situ observation of ultrafast 90° domain switching under application of an electric field in (100)/(001)-oriented tetragonal epitaxial Pb(ZrTi)O thin films.

Ferroelastic domain switching significantly affects piezoelectric properties in ferroelectric materials. The ferroelastic domain switching and the lattice deformation of both a-domains and c-domains under an applied electric field were investigated using in-situ synchrotron X-ray diffraction in conjunction with a high-speed pulse generator set up for epitaxial (100)/(001)-oriented tetragonal Pb(ZrTi)O (PZT) films grown on (100) SrRuO//(100)KTaO substrates. The 004 peak (c-domain) position shifts to a lower 2θ angle, which demonstrates the elongation of the c-axis lattice parameter of the c-domain under an applied electric field.

Extended Polymorphism of Two-Dimensional Material.

When controlling electronic properties of bulk materials, we usually assume that the basic crystal structure is fixed. However, in two-dimensional (2D) materials, atomic structure or polymorph is attracting growing interest as a controlling parameter to functionalize their properties. Various polymorphs can exist in transition metal dichalcogenides (TMDCs) from which 2D materials are generated, and polymorphism has drastic impacts on the electronic states.

Tomographic Mapping Analysis in the Depth Direction of High-Ge-Content SiGe Layers with Compositionally Graded Buffers Using Nanobeam X-ray Diffraction.

A high-Ge-content SiGe/compositionally graded SiGe-stacked structure grown on Si(001) is now considered to be an important platform for the realization of advanced nanometer-scale complementary metal oxide semiconductor devices with high-mobility channel materials, such as III-V materials and Ge, and monolithically integrated photonic modules. The performance of such advanced devices is critically influenced by crystalline inhomogeneity in the stacked structure; therefore, precise characterization of the crystallinity is important. In particular, the development of a characterization method not only for in-plane crystallinity but also for in-depth crystallinity is strongly required.

⁵⁷Fe polarization-dependent synchrotron Mössbauer spectroscopy using a diamond phase plate and an iron borate nuclear Bragg monochromator.

Energy-domain (57)Fe polarization-dependent synchrotron radiation Mössbauer spectroscopy was developed by using a diamond X-ray phase plate and an iron borate nuclear Bragg monochromator. The former controls the polarization of the incident synchrotron radiation X-rays and the latter filters the (57)Fe-Mössbauer radiation with a narrow bandwidth of ∼3.4 Γ0 (Γ0 ≃ 4.

Controlling charge-density-wave states in nano-thick crystals of 1T-TaS2.

Two-dimensional crystals, especially graphene and transition metal dichalcogenides (TMDs), are attracting growing interests because they provide an ideal platform for novel and unconventional electronic band structures derived by thinning. The thinning may also affect collective phenomena of electrons in interacting electron systems and can lead to exotic states beyond the simple band picture. Here, we report the systematic control of charge-density-wave (CDW) transitions by changing thickness, cooling rate and gate voltage in nano-thick crystals of 1T-type tantalum disulfide (1T-TaS2).

Impact of voglibose on the pharmacokinetics of dapagliflozin in Japanese patients with type 2 diabetes.

Introduction: Dapagliflozin is an orally administered selective sodium-glucose cotransporter 2 (SGLT2) inhibitor under development for the treatment of type 2 diabetes mellitus (T2DM). Dapagliflozin lowers blood glucose through a reduction in renal glucose reabsorption. This study was performed to assess the effect of the oral antidiabetic agent voglibose [0.

Polarization-dependent X-ray six-beam pinhole topographs for a channel-cut silicon crystal.

It was pointed out in a previous paper [Okitsu et al. (2006), Acta Cryst. A62, 237-244] that an n-beam Takagi-Taupin (T-T) equation can be solved for a crystal of arbitrary shape.

Model-based determination of abatacept exposure in support of the recommended dose for Japanese rheumatoid arthritis patients.

The objective of this study was to provide support for a body weight-tiered dosing regimen by characterizing abatacept pharmacokinetics (PK) and the relationship between exposure and the ACR20 (American College of Rheumatology criteria for 20% improvement) response in Japanese patients with rheumatoid arthritis (RA). A population PK model was developed using NONMEM with 2,535 samples from 344 Japanese RA patients in two clinical trials. The exposure-response relationship was characterized using a Generalized Estimating Equation (GEE) logistic regression model, with time-varying actual trough concentrations and ACR20 responder rates over 6 months in a randomized, placebo-controlled phase 2 trial for stable methotrexate.

In situ and real-time monitoring of oxide growth in a few monolayers at surfaces of platinum nanoparticles in aqueous media.

The electrochemical oxidation behaviors of the surfaces of platinum nanoparticles, one of the key phenomena in fuel cell developments, were investigated in situ and in real time, via time-resolved hard X-ray diffraction and energy dispersive X-ray absorption spectroscopy. Combining two complementary structural analyses, dynamical and inhomogenous structural changes occurring at the surfaces of nanoparticles were monitored on an atomic level with a time resolution of less than 1 s. After oxidation at 1.

Dose distribution of a 125 keV mean energy microplanar x-ray beam for basic studies on microbeam radiotherapy.

A multislit collimator was designed and fabricated for basic studies on microbeam radiation therapy (MRT) with an x-ray energy of about 100 keV. It consists of 30 slits that are 25 microm high, 30 mm wide, and 5 mm thick in the beam direction. The slits were made of 25 microm-thick polyimide sheets that were separated by 175 microm-thick tungsten sheets.

Polarization-dependent six-beam X-ray pinhole topographs.

X-ray six-beam pinhole topograph images were obtained for a silicon crystal with incident synchrotron X-rays. The polarization state of X-rays incident on the sample crystal was controlled by using a four-quadrant phase-retarder system [Okitsu et al. (2002).

'Six-beam X-ray section topograph' images and computer-simulated images using the new n-beam dynamical theory based on the Takagi-Taupin equations.

A 'six-beam X-ray section topograph' experiment was performed whose images are in excellent agreement with the images computer-simulated using the theory derived by one of the authors [Okitsu (2003). Acta Cryst. A59, 235-244] based on the Takagi-Taupin dynamical theory.