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An optimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during atrial fibrillation (AF) ablation. Limited data are available on the uninterrupted use of apixaban in patients with AF undergoing catheter ablation. This study aimed to evaluate the safety and efficacy of uninterrupted apixaban in patients undergoing radiofrequency ablation for AF. In particular, we evaluated silent cerebral infarction (CI) during radiofrequency catheter ablation of AF. This was a prospective and nonrandomized cohort study. A total of 259 consecutive patients who underwent AF ablation were evaluated; 157 patients received apixaban (Api group), and 102 patients received dose-adjusted (PT-INR 2.0-3.0) warfarin (Wf group). All oral anticoagulants were continued throughout the periprocedural period, including the morning of the procedure. Intravenous heparin was administered during the procedure and neutralized by protamine at the end of the procedure. Sixty-one patients underwent magnetic resonance imaging (MRI) after the procedure to evaluate for silent CI. Mean age was 66 ± 11 years; there were 91 men (73.7%) and 148 cases of paroxysmal AF (57.1%). No symptomatic CI was observed. Silent CI occurred in 6/61 patients (9.8%). No significant difference was observed between the Api group (4/30 patients, 13.3%) and the Wf group (2/31 patients, 6.5%). There was no significant difference regarding major bleeding events between the Api group (1/157 patients, 0.6%) and the Wf group (2/102 patients, 2.0%). The safety and efficacy of uninterrupted apixaban for patients undergoing AF ablation were equivalent to warfarin for preventing bleeding and thromboembolic complications.

We developed a transportable Linnik-type full-field low-coherent quantitative phase microscope that is able to compensate for optical path length (OPL) disturbance due to environmental mechanical noises. Though two-beam interferometers such as Linnik ones suffer from unstable OPL difference, we overcame this problem with a mechanical feedback system based on digital signal-processing that controls the OPL difference in sub-nanometer resolution precisely with a feedback bandwidth of 4 kHz. The developed setup has a footprint of 200 mm by 200 mm, a height of 500 mm, and a weight of 4.5 kilograms. In the transmission imaging mode, cells were cultured on a reflection-enhanced glass-bottom dish, and we obtained interference images sequentially while performing stepwise quarter-wavelength phase-shifting. Real-time image processing, including retrieval of the unwrapped phase from interference images and its background correction, along with the acquisition of interference images, was performed on a laptop computer. Emulation of the phase contrast (PhC) images and the differential interference contrast (DIC) images was also performed in real time. Moreover, our setup was applied for full-field cell membrane imaging in the reflection mode, where the cells were cultured on an anti-reflection (AR)-coated glass-bottom dish. The phase and intensity of the light reflected by the membrane revealed the outer shape of the cells independent of the refractive index. In this paper, we show imaging results on cultured cells in both transmission and reflection modes.

We propose a new 1π sr Wide Acceptance Angle Electrostatic Lens (WAAEL), which works as a photoemission electron microscope (PEEM), a highly sensitive display-type electron energy and two-dimensional angular distribution analyzer. It can display two-dimensional angular distributions of charged particles within the acceptance angle of ±60° that is much larger than the largest acceptance angle range so far and comparable to the display-type spherical mirror analyzer developed by Daimon et al. [1] . It has good focusing capabilities with 5-times magnification and 27(4) μm lateral-resolution. The relative energy resolution is typically from 2 to 5×10–3 depending on the diameter of energy aperture and the emission area on the sample. Although, the lateral resolution of the presented lens is far from those are available nowadays, but this is the first working model that can form images using charged particles collected from 1π sr wide acceptance angle. The realization of such lens system is one of the first possible steps towards reaching the field of imaging type atomic resolution electron microscopy Feynman et al. [2] . Here some preliminary results are shown.

We developed a portable and user-friendly prototype of low-coherent reflection-type quantitative phase microscope (QPM). Our setup is based on the full-field Linnik type phase-shifting interference microscope and is optimized for surface profiling of living cell’s membrane. Unlike commonly available transmission-type quantitative phase microscopes which reveal the optical thickness, our reflection-type setup can obtain the geometrical thickness (real shape) of the sample, decoupled with the refractive index. The coherence length of our imaging light source (halogen lamp) was approximately 1 micrometer so that we can selectively obtain the interference of the light reflected from the cell membranes whose reflectivity in culture medium is only on the order of 0.1%. Moreover our setup has a feedback controlled path-length stabilization circuit so that users can implement accurate phase shifting interferometry with one nanometer of reproducibility. The stabilization circuit allows installing our setup even in noisy environments such as biology labs without an optical bench. In this paper, we will also show our studies of recent biomedical applications, including imaging of cell plasma membrane and phase-resolved 3D tomography of living cells.

A prototype of a pneumatic injector of hydrogen cryogenic pellets with controlled length is under development at Kyushu University. The major element of the prototype is a remote cylindrical freezing cavity with controllable length which allows the length of a frozen hydrogen pellet formed in situ to be adjusted precisely and continuously from sub-millimeter to a few millimeters. The design and operation of the prototype are described. The initial results of experimental adjustment of the pellet length are also reported. The length of 1.4 mm diameter hydrogen ice pellets has been varied continuously from 0.5 to 3.0 mm at a temperature range of 6–9 K. The prototype has launched single solid pellet with controlled length through room temperature helium gas at a pressure of 0.5–2 MPa.

We have developed a new method, “stereo-atomscope”, to obtain a stereophotograph of the three-dimensional atomic arrangement around a specific atom at the surface, with which one can view the three-dimensional atomic arrangement directly by naked eyes. The azimuthal shifts of forward focusing peaks in the photoelectron angular distribution pattern obtained with left and right helicity lights are the same as the parallax in a stereo-view. Taking advantage of this phenomenon of circular dichroism in the photoelectron angular distribution, one can realize a stereoscope of atomic arrangement. A display-type spherical-mirror analyzer has been used to obtain stereoscopic photographs directly on the screen without any computer-aided conversion process.

There is an increasing need for non-invasive imaging techniques in the field of stem cell research. Label-free techniques are the best choice for assessment of stem cells because the cells remain intact after imaging and can be used for further studies such as differentiation induction. To develop a high-resolution label-free imaging system, we have been working on a low-coherence quantitative phase microscope (LC-QPM). LC-QPM is a Linnik-type interference microscope equipped with nanometer-resolution optical-path-length control and capable of obtaining three-dimensional volumetric images. The lateral and vertical resolutions of our system are respectively 0.5 and 0.93 μm and this performance allows capturing sub-cellular morphological features of live cells without labeling. Utilizing LC-QPM, we reported on three-dimensional imaging of membrane fluctuations, dynamics of filopodia, and motions of intracellular organelles. In this presentation, we report three-dimensional morphological imaging of human induced pluripotent stem cells (hiPS cells). Two groups of monolayer hiPS cell cultures were prepared so that one group was cultured in a suitable culture medium that kept the cells undifferentiated, and the other group was cultured in a medium supplemented with retinoic acid, which forces the stem cells to differentiate. The volumetric images of the 2 groups show distinctive differences, especially in surface roughness. We believe that our LC-QPM system will prove useful in assessing many other stem cell conditions.

N -Oxyl-mediated electrooxidation of alcohols was performed in an aqueous silica gel disperse system. The newly devised electrolysis system offers an organic solvent-free and operationally simple procedure for oxidation of alcohols and could be successfully applied to kinetic resolution of sec -alcohol as well as enantioselective oxidation of meso -1,4-diol affording optically active γ-lactone.

Background: Recent technological advances have enabled the reliable detection and characterization of circulating tumor cells (CTCs) in the blood of cancer patients. To quantify the amount of CTCs, various assays have been developed to facilitate the detection of epithelial cells in the blood by using cellular surface markers such as EpCAM and cytokeratins. However, recent studies have revealed the importance of CTCs undergoing epithelial-mesenchymal transition (EMT), which are difficult to detect by the conventional surface marker-based methods because those CTCs express low expression of epithelial markers. We previously reported a novel method for the identification of CTCs by removing WBCs from mononuclear cells in the blood, based on the features of Quantitative Phase Microscope Images (QPIs) of the cells obtained from machine-learning (AACR Annual Meeting 2015). Here, we report some progress of our study. Methods: We analyzed WBCs and cancer cell lines using Quantitative Phase Microscope (QPM) that can image optical path-length of living cells with a high resolution of 1nm without staining in non-cytotoxic way. At this time, QPIs were reconstructed from line scanned images of the cells flowing in a chamber. Obtained QPIs were analyzed by a computer vision application which automatically identifies an object in digital images based on the features extracted from the dataset we had developed by machine learning. Results: We imaged 325 WBCs obtained from healthy donors and 325 cell-line cells (from 5 cancer cell lines) with QPM. Then, we extracted certain features from the QPIs and used them as training images for machine learning. We employed 5-fold cross validation to create an algorithm to detect WBCs circulating in the blood. The algorithm successfully recognized WBCs among QPIs mixed in with WBCs and cancer cell lines. The ROC AUC value was 0.98, indicating that the algorithm was not a random selection. Furthermore, we successfully captured QPIs of the flowing cells, which makes it possible to sort living cells based on the algorithm we developed. Conclusions: We successfully differentiated WBCs from cancer cell lines based on the features of QPIs. The object recognition method applying to QPIs of the cell is expected as a useful, non-cytotoxic, marker-free isolation of CTCs. Citation Format: Yusuke Ozaki, Hidenao Yamada, Hirotoshi Kikuchi, Tomohiro Murakami, Tomhiro Matsumoto, Toshiki Kawabata, Yoshihiro Hiramatsu, Manabu Ohta, Kinji Kamiya, Megumi Baba, Toyohiko Yamauchi, Kentaro Goto, Yukio Ueda, Shigetoshi Okazaki, Hiroyuki Konno. Label-free imaging identification of WBCs based on the features of quantitative phase microscope images for negative selection of CTCs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3952.

Semiconductor manufacturing technology is currently undergoing a transformation from immersion photolithography to double patterning or EUV technology. The resultant resist dimensional size and height shrinks will require improved pattern transfer techniques and materials. Underlayer (UL) processes which include chemical vapor deposition (CVD) and spin-on application play a very important role in various chip manufacturing integration schemes. A pattern wiggling problem during substrate etch has arisen as a critical issue when pattern dimensions shrink. CVD processes have shown better pattern transfer performance than spin-on processes but at higher cost and process complexity along with difficulty in obtaining planarization and good gap fill. Thus spin-on process development has received increased attention recently as an attractive alternative to CVD processing. In this work we focus on elucidating the mechanism of UL wiggling and have synthesized materials that address several hypothesized mechanisms of failure: hydrogen content, modulus, film density, charge control unit type and thermal resistance. UL materials with high thermal resistance additionally provide the ability to expand the applicability of spin-on approaches. Material properties and wiggle failure test results will be discussed.

Extreme ultraviolet (EUV) lithography is one of the most promising technologies for achieving 22nm HP lithography and beyond. EUV resist is required to improve resolution limit down to less than 20nm hp. To achieve such a performance, innovative materials' development is necessary under ultra-thin resist film condition for preventing line collapse. In addition, more refined etching processes compatible with ultra-thin resist film are needed. In this study, we will report our several approaches for both materials and processes towards forming less than 20nm HP pattern under ultra-thin film condition. We will also introduce our tri-layer system formed with combination of Si-ARC stack and organic hard mask (OHM) stack for refined etching process.

In order to achieve targeted resist performance for EUV in practical applications, we have developed new materials such as molecular glass (MG), PAG, and acid amplifiers (AA). Protected NORIA, a molecular glass, was examined for extending resolution limits. The resist with protected NORIA showed 22 nm hp resolutions under EUV exposure. PAG acid diffusion effect on LWR was also investigated. It was found that acid diffusion control was one of the most important factors for LWR improvement. To improve sensitivity, application of AA (acid amplifier) was investigated. The resist with AA gained 25% sensitivity improvement over the original formulation. Elemental technologies for major progress of EUV resist were made.

It has been found that 193nm immersion lithography technology can achieve smaller patterns without any modification to the technology infrastructure of existing state-of-the-art 193nm dry lithography. This has made 193nm immersion lithography a promising technology for mass production processes. Recently, scanning speed of the exposure stage has been increasing in order to achieve high throughput for mass production. At present, the adoption of a topcoat is one of the promising candidates for this high speed scanning process. On the other hand, the demand for a non-topcoat process is being pursued from a C.O.O. (cost of ownership) point of view but there are still issues being revealed and concerns to be solved. In this report, feasibility of a comprehensive process for high scanning ArF immersion lithography was discussed. As for the topcoat process, a high receding contact angle topcoat, such as TC-A (JSR), is proving to be a good candidate for mass production using high scanning speed immersion lithography. TC-A has a similar defectivity and lithographic performance to TCX041 (JSR). On the other hand, the feasibility of a non-topcoat process was also investigated. CD uniformity, defectivity and lithography performance of AIM5120JN and AIM5570JN (JSR) data indicate that the non-topcoat process can be adopted for mass production process. An immersion cluster comprised of a high volume production immersion exposure tool, S610C (NIKON) having 1.3 NA and CLEAN TRACK TM LITHIUS TM i+ (TEL) track system were used in this study.

N -Oxyl-mediated electrooxidation of alcohols was performed in an aqueous silica gel disperse system. The newly devised electrolysis system offers an organic solvent-free and operationally simple procedure for oxidation of alcohols and could be successfully applied to kinetic resolution of sec -alcohol as well as enantioselective oxidation of meso -1,4-diol affording optically active γ-lactone.

Photoelectron holography has been expected to be a powerful tool for visualizing three-dimensional (3D) local atomic structures around a photoelectron emitter atom. Photoelectron emitter atom sites with different elements can be distinguished by photoelectron kinetic energy. The elements of atoms reconstructed in atomic images, however, could not be assigned. We developed a method for the elemental characterization of the reconstructed atoms using a small difference of the scattered electron waves and demonstrated it using a measured InP(001) photoelectron hologram. Element assignment for both the emitter atom and the reconstructed atoms in 3D atomic images became possible.

A large diameter diaphragmless shock tube has been recently developed and designed to perform detailed studies of CO2-N2 gas-dynamic laser (GDL). This large diameter diaphragmless shock tube offers various advantages over the conventional shock tubes (diaphragm-type) as longer test times, higher degree of reproducibility of shock-tube data, and especially low-impurity operation condition. The latter advantage is experimentally demonstrated herein, which is very critical issue in the CO2-N2 GDL studies. A supersonic nozzle section was mounted at the end wall of the shock tube and instrumented for simultaneous measurement of laser output power and energy. The GDL action in a CO2-N2 mixture under low impurity condition has been obtained by using the large diameter diaphragmless shock tube for the first time.