Development of Neutron Interferometer Using Multilayer Mirrors and Measurements of Neutron-Nuclear Scattering Length with Pulsed Neutron Source.

This study entailed the successful deployment of a novel neutron interferometer that utilizes multilayer mirrors. The apparatus facilitates a precise evaluation of the wavelength dependence of interference fringes utilizing a pulsed neutron source. Our interferometer achieved an impressive precision of 0.02 rad within a 20-min recording time. Compared to systems using silicon crystals, the measurement sensitivity was maintained even when using a simplified disturbance suppressor. By segregating beam paths entirely, we achieved successful measurements of neutron-nuclear scattering lengths across various samples. The values measured for Si, Al, and Ti were in agreement with those found in the literature, while V showed a disparity of 45%. This discrepancy may be attributable to impurities encountered in previous investigations. The accuracy of measurements can be enhanced further by mitigating systematic uncertainties that are associated with neutron wavelength, sample impurity, and thickness. This novel neutron interferometer enables us to measure fundamental parameters, such as the neutron-nuclear scattering length of materials, with a precision that surpasses that of conventional interferometers.

Single-shot optical imaging with spectrum circuit bridging timescales in high-speed photography.

Single-shot optical imaging based on ultrashort lasers has revealed nonrepetitive processes in subnanosecond timescales beyond the recording range of conventional high-speed cameras. However, nanosecond photography without sacrificing short exposure time and image quality is still missing because of the gap in recordable timescales between ultrafast optical imaging and high-speed electronic cameras. Here, we demonstrate nanosecond photography and ultrawide time-range high-speed photography using a spectrum circuit that produces interval-tunable pulse trains while keeping short pulse durations. We capture a shock wave propagating through a biological cell with a 1.5-ns frame interval and 44-ps exposure time while suppressing image blur. Furthermore, we observe femtosecond laser processing over multiple timescales (25-ps, 2.0-ns, and 1-ms frame intervals), showing that the plasma generated at the picosecond timescale affects subsequent shock wave formation at the nanosecond timescale. Our technique contributes to accumulating data of various fast processes for analysis and to analyzing multi-timescale phenomena as a series of physical processes.

A Novel Riboflavin Formulation for Corneal Delivery Without Damaging Epithelial Cells.

Purpose: This study aimed to evaluate the trans-epithelial permeability enhancement and cell damage caused by a novel riboflavin composition for corneal delivery. Methods: We developed a trans-epithelial formulation of riboflavin for corneal delivery using 1,2-dioleoyl-3-dimethylammonium-propane (DODAP) and isostearic acid (ISA). The permeation enhancement was evaluated using an in vitro corneal epithelial cell culture system by measuring the amount of transferred riboflavin with high-performance liquid chromatography. Riboflavin permeation of MedioCROSS TE, a commercially available riboflavin formulation containing benzalkonium chloride, was also evaluated and compared to that of the DODAP/ISA formulation by changing the riboflavin concentration. The trans-epithelial electrical resistance (TEER) was measured after exposure to the samples in an in vitro corneal epithelial cell culture system to assess cytotoxicity. Results: The DODAP/ISA formulation demonstrated greater permeation when used together than when each component was used individually. The permeation enhancement effect of the DODAP/ISA formulation was almost the same as that of MedioCROSS TE. However, when a 10-fold higher riboflavin concentration was used in the DODAP/ISA formulation, the permeation enhancement effect surpassed that of MedioCROSS TE. After 24 hours of exposure, the TEER of the DODAP/ISA formulation was higher than that of MedioCROSS TE, indicating that the DODAP/ISA formulation was less cytotoxic than MedioCROSS TE. Conclusions: This study indicated that the DODAP/ISA formulation could serve as a less cytotoxic alternative to MedioCROSS TE. Further studies are required to determine the clinical efficacy and safety of the DODAP/ISA formulation in vivo. Translational Relevance: This study may provide alternative procedures for corneal collagen crosslinking with less of a cytotoxic effect on corneal epithelial cells.

Response to an applied electric field in an antiferroelectric 1/2 subphase: The role of thermal fluctuations.

The response to an applied electric field in the q_{T}=1/2 subphase of the MC881-MC452 binary mixture system is studied by using thick homeotropically aligned cells. In the ordinary antiferroelectric SmC_{A}^{*} and 1/2 (sub)phases, some nonplanar asymmetric distortions in the antiferroelectric unit cell structure produce induced polarization in the applied field direction, starts to unwind the helix from the beginning, and tends to align the averaged tilt plane direction parallel to the applied field. In the 1/2 subphase under consideration, however, the helix resists being deformed at the beginning and then the thresholdlike steep increase of birefringence Δn occurs in the transition from 1/2 to unwound SmC^{*} at a field of less than 0.5 V/µm; we conclude that the thermal fluctuations play an important role in promoting the director flip-flopping in a single layer under the applied field and bring about additional induced polarization, which counteracts the aforementioned ordinary induced one and prevents the helix from unwinding. This suggests that the Langevin-like director reorientation is the mechanism of the V-shaped switching which was actually observed in the thin films of Mitsui mixture [Phys. Rev. Lett. 87, 015701 (2001)0031-900710.1103/PhysRevLett.87.015701] and must have been used in prototyped thresholdless antiferroelectric liquid-crystal displays.

Agarose gel microcapsules enable easy-to-prepare, picolitre-scale, single-cell genomics, yielding high-coverage genome sequences.

A novel type of agarose gel microcapsule (AGM), consisting of an alginate picolitre sol core and an agarose gel shell, was developed to obtain high-quality, single-cell, amplified genomic DNA of bacteria. The AGM is easy to prepare in a stable emulsion with oil of water-equivalent density, which prevents AGM aggregation, with only standard laboratory equipment. Single cells from a pure culture of Escherichia coli, a mock community comprising 15 strains of human gut bacteria, and a termite gut bacterial community were encapsulated within AGMs, and their genomic DNA samples were prepared with massively parallel amplifications in a tube. The genome sequencing did not need second-round amplification and showed an average genome completeness that was much higher than that obtained using a conventional amplification method on the microlitre scale, regardless of the genomic guanine-cytosine content. Our novel method using AGM will allow many researchers to perform single-cell genomics easily and effectively, and can accelerate genomic analysis of yet-uncultured microorganisms.

Appropriate tension sensitivity of α-catenin ensures rounding morphogenesis of epithelial spheroids.

The adherens junction (AJ) is an actin filament-anchoring junction. It plays a central role in epithelial morphogenesis through cadherin-based recognition and adhesion among cells. The stability and plasticity of AJs are required for the morphogenesis. An actin-binding α-catenin is an essential component of the cadherin-catenin complex and functions as a tension transducer that changes its conformation and induces AJ development in response to tension. Despite much progress in understanding molecular mechanisms of tension sensitivity of α-catenin, its significance on epithelial morphogenesis is still unknown. Here we show that the tension sensitivity of α-catenin is essential for epithelial cells to form round spheroids through proper multicellular rearrangement. Using a novel in vitro suspension culture model, we found that epithelial cells form round spheroids even from rectangular-shaped cell masses with high aspect ratios without using high tension and that increased tension sensitivity of α-catenin affected this morphogenesis. Analyses of AJ formation and cellular tracking during rounding morphogenesis showed cellular rearrangement, probably through AJ remodeling. The rearrangement occurs at the cell mass level, but not single-cell level. Hypersensitive α-catenin mutant-expressing cells did not show cellular rearrangement at the cell mass level, suggesting that the appropriate tension sensitivity of α-catenin is crucial for the coordinated round morphogenesis.Key words: α-catenin, vinculin, adherens junction, morphogenesis, mechanotransduction.

Pendellösung interferometry probes the neutron charge radius, lattice dynamics, and fifth forces.

Structure factors describe how incident radiation is scattered from materials such as silicon and germanium and characterize the physical interaction between the material and scattered particles. We used neutron Pendellösung interferometry to make precision measurements of the (220) and (400) neutron-silicon structure factors and achieved a factor-of-four improvement in the (111) structure factor uncertainty. These data provide measurements of the silicon Debye-Waller factor at room temperature and the mean square neutron charge radius rn2=−0.1101±0.0089 square femtometers. Combined with existing measurements of the Debye-Waller factor and charge radius, the measured structure factors also improve constraints on the strength of a Yukawa modification to gravity by an order of magnitude over the 20 picometer­to­10 nanometer length scale range.

Application of precise neutron focusing mirrors for neutron reflectometry: latest results and future prospects.

Neutron reflectometry (NR) is a powerful tool for providing insight into the evolution of interfacial structures, for example via operando measurements for electrode-electrolyte interfaces, with a spatial resolution of nanometres. The time resolution of NR, which ranges from seconds to minutes depending on the reflection intensity, unfortunately remains low, particularly for small samples made of state-of-the-art materials even with the latest neutron reflectometers. To overcome this problem, a large-area focusing supermirror manufactured with ultra-precision machining has been employed to enhance the neutron flux at the sample, and a gain of approximately 100% in the neutron flux was achieved. Using this mirror, a reflectivity measurement was performed on a thin cathode film on an SrTiO3 substrate in contact with an electrolyte with a small area of 15 × 15 mm. The reflectivity data obtained with the focusing mirror were consistent with those without the mirror, but the acquisition time was shortened to half that of the original, which is an important milestone for rapid measurements with a limited reciprocal space. Furthermore, a method for further upgrades that will reveal the structural evolution with a wide reciprocal space is proposed, by applying this mirror for multi-incident-angle neutron reflectometry.

Sequentially timed all-optical mapping photography boosted by a branched 4f system with a slicing mirror.

We present sequentially timed all-optical mapping photography (STAMP) with a slicing mirror in a branched 4f system for an increased number of frames without sacrificing pixel resolution. The branched 4f system spectrally separates the laser light path into multiple paths by the slicing mirror placed in the Fourier plane. Fabricated by an ultra-precision end milling process, the slicing mirror has 18 mirror facets of differing mirror angles. We used the boosted STAMP to observe dynamics of laser ablation with two image sensors which captured 18 subsequent frames at a frame rate of 126 billion frames per second, demonstrating this technique's potential for imaging unexplored ultrafast non-repetitive phenomena.

Elliptic neutron-focusing supermirror for illuminating small samples in neutron reflectometry.

This paper details the development of a precise assembly of two supermirrors for neutron-focusing, designed for installation in neutron reflectometer SOFIA at BL16 in J-PARC MLF to intensify the illumination for small samples. The supermirrors are sputtered on two metal substrates, whose surfaces are coated with amorphous Ni-P plating, and are figured by diamond cutting and polished to subnanometer roughness. Special care is taken while polishing the substrates to reduce waviness and surface roughness for achieving a sharp focusing spot and uniform neutron reflectivity. The supermirror could converge the neutrons into a focal spot with a width of 0.13 mm in the full width at half maximum.

Measurement and alleviation of subsurface damage in a thick-crystal neutron interferometer.

The construction is described of a monolithic thick-crystal perfect silicon neutron interferometer using an ultra-high-precision grinding technique and a combination of annealing and chemical etching that differs from the construction of prior neutron interferometers. The interferometer is the second to have been annealed after machining and the first to be annealed prior to chemical etching. Monitoring the interference signal at each post-fabrication step provides a measurement of subsurface damage and its alleviation. In this case, the strain caused by subsurface damage manifests itself as a spatially varying angular misalignment between the two relevant volumes of the crystal and is reduced from ∼10-5 rad to ∼10-9 rad by way of annealing and chemical etching.

Characterization of all second-order nonlinear-optical coefficients of organic N-benzyl-2-methyl-4-nitroaniline crystal.

Full elements of second-order nonlinear optical (NLO) tensor can be completely characterized for an organic NLO crystal for the first time. As-grown bulk N-benzyl-2-methyl-4-nitroaniline (BNA) crystal was processed to expose (100) and (010) crystal orientations with fine optical surfaces by using precision lathe and diamond blade. Then, every five nonvanishing second-order NLO coefficient of BNA can be determined quantitatively using the precisely processed crystals based on 1st-kind Maker fringe measurements. Our method makes it possible to clarify uncertain NLO property of any organic materials and to accelerate application study via precise device fabrications even for fragile organic materials.

In vitro analysis of blood flow in a microvascular network with realistic geometry.

In vitro blood flow was measured in a polydimethysiloxane micro channel to reflect the complex geometry of a microvascular network. Flow rates were determined from the velocities of tracer particles moving along the center line of the flow channel, and the flow rates of two working fluids were then compared: water and blood. In some bifurcating channels, the measured flow rate showed that the effects of bifurcation in the apparent viscosity depend on the hematocrit, such that the flow rate in the daughter channel with the higher (lower) flow rate was lower (higher) for blood than for water. The measured flow rates in other bifurcating channels reflected effects from the surrounding flow channels acting as bypasses, which tended to balance out the effects of bifurcation.

Shielding design of a target station and radiation dose level investigation of proton linac for a compact accelerator-driven neutron source applied at industrial sites.

The shielding design for a compact accelerator-driven neutron source (CANS) that is applied in industries was studied using both theoretical simulations and experimental measurements. Neutron shielding material composition for CANS was optimized by coupling the genetic algorithm with the Monte Carlo code. A multi-layer shielding structure was developed and successfully applied to a CANS target station. The high radiation dose of CANS proton linac was investigated in detail on the basis of experimental measurements, and the radiation dose was significantly reduced by replacing the material of its bellow pipes.

Development of precision elliptic neutron-focusing supermirror.

This paper details methods for the precision design and fabrication of neutron-focusing supermirrors, based on electroless nickel plating. We fabricated an elliptic mirror for neutron reflectometry, which is our second mirror improved from the first. The mirror is a 550-millimeter-long segmented mirror assembled using kinematic couplings, with each segment figured by diamond cutting, polished using colloidal silica, and supermirror coated through ion-beam sputtering. The mirror was evaluated with neutron beams, and the reflectivity was found to be 68-90% at a critical angle. The focusing width was 0.17 mm at the full width at half maximum.

A Perturbation Analysis to Understand the Mechanism How Migrating Cells Sense and Respond to a Topography in the Extracellular Environment.

Migrating cells in vivo monitor the physiological state of an organism by integrating the physical as well as chemical cues in the extracellular microenvironment, and alter the migration mode, in order to achieve their unique function. The clarification of the mechanism focusing on the topographical cues is important for basic biological research, and for biomedical engineering specifically to establish the design concept of tissue engineering scaffolds. The aim of this study is to understand how cells sense and respond to the complex topographical cues in vivo by exploring in vitro analyses to complex in vivo situations in order to simplify the issue. Since the intracellular mechanical events at subcellular scales and the way of the coordination of these events are supposed to change in the migrating cells, a key to success of the analysis is a mechanical point of view with a particular focus of the subcellular mechanical events. We designed an experimental platform to explore the mechanical requirements in a migrating fibroma cell responding to micro-grooves. The micro-grooved structure is a model of gap structures, typically seen in the microenvironments in vivo. In our experiment, the contributions of actomyosin force generation can be spatially divided and analyzed in the cell center and peripheral regions. The analysis specified that rapid leading edge protrusion, and the cell body translocation coordinated with the leading edge protrusion are required for the turning response at a micro-groove.

Development of a large plano-elliptical neutron-focusing supermirror with metallic substrates.

Results of this study demonstrated that electroless nickel-phosphorus (NiP) plated metal substrate is an excellent material for producing large aspherical neutron-focusing supermirrors. A large plano-elliptical neutron-focusing supermirror comprising two metallic segments was fabricated using single-point diamond cutting, precision polishing and supermirror coating. The average surface roughness of the metallic substrates was approximately 0.3 nm rms. For evaluation, the focusing supermirror was installed at the SOFIA neutron reflectometer, showing high neutron reflectivity and giving minimal beam width of 0.34 mm in FWHM. Because of the large beam divergence accepted by the mirror, the count rate with the focusing mirror was 3.3 times higher than that obtained using conventional two-slit collimation.

Figure correction of a metallic ellipsoidal neutron focusing mirror.

An increasing number of neutron focusing mirrors is being adopted in neutron scattering experiments in order to provide high fluxes at sample positions, reduce measurement time, and/or increase statistical reliability. To realize a small focusing spot and high beam intensity, mirrors with both high form accuracy and low surface roughness are required. To achieve this, we propose a new figure correction technique to fabricate a two-dimensional neutron focusing mirror made with electroless nickel-phosphorus (NiP) by effectively combining ultraprecision shaper cutting and fine polishing. An arc envelope shaper cutting method is introduced to generate high form accuracy, while a fine polishing method, in which the material is removed effectively without losing profile accuracy, is developed to reduce the surface roughness of the mirror. High form accuracy in the minor-axis and the major-axis is obtained through tool profile error compensation and corrective polishing, respectively, and low surface roughness is acquired under a low polishing load. As a result, an ellipsoidal neutron focusing mirror is successfully fabricated with high form accuracy of 0.5 µm peak-to-valley and low surface roughness of 0.2 nm root-mean-square.

New fabrication method for an ellipsoidal neutron focusing mirror with a metal substrate.

We propose an ellipsoidal neutron focusing mirror using a metal substrate made with electroless nickel-phosphorus (NiP) plated material for the first time. Electroless NiP has great advantages for realizing an ellipsoidal neutron mirror because of its amorphous structure, good machinability and relatively large critical angle of total reflection for neutrons. We manufactured the mirror by combining ultrahigh precision cutting and fine polishing to generate high form accuracy and low surface roughness. The form accuracy of the mirror was estimated to be 5.3 µm P-V and 0.8 µm P-V for the minor-axis and major-axis direction respectively, while the surface roughness was reduced to 0.2 nm rms. The effect of form error on focusing spot size was evaluated by using a laser beam and the focusing performance of the mirror was verified by neutron experiments.

Characteristics of motility-based filtering of adherent cells on microgrooved surfaces.

Topographical features are known to physically affect cell behavior and are expected to have great potential for non-invasive control of such behavior. To provide a design concept of a microstructured surface for elaborate non-invasive control of cell migration, we systematically analyzed the effect of microgrooves on cell migration. We fabricated silicon microstructured surfaces covered with SiO(2) with microgrooves of various sizes, and characterized the behavior of cells moving from the flat surface to the grooved surface. The intersecting microgrooves with well-defined groove width absorbed or repelled cells precisely according to the angle of approach of the cell to the boundary with the grooved surface. This filtering process was explained by the difference in the magnitude of the lamellar dragging effect resulting from the number of the grooves interacting with the lamella of the cell. This study provides a framework to tailor the microgrooved surface for non-invasive control of cell migration with label-free detection of a specific property of the target cells. This should offer significant benefits to biomedical research and applications.