A phase I study of high dose camostat mesylate in healthy adults provides a rationale to repurpose the TMPRSS2 inhibitor for the treatment of COVID-19.

Camostat mesylate, an oral serine protease inhibitor, is used to treat chronic pancreatitis and reflux esophagitis. Recently, camostat mesylate and its active metabolite 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA) were reported to inhibit the infection of cells by severe acute respiratory syndrome coronavirus 2 by inhibiting type II transmembrane serine protease. We conducted a phase I study to investigate high-dose camostat mesylate as a treatment for coronavirus disease 2019. Camostat mesylate was orally administered to healthy adults at 600 mg 4 times daily under either of the following conditions: fasted state, after a meal, 30 min before a meal, or 1 h before a meal, and the pharmacokinetics and safety profiles were evaluated. In addition, the time of plasma GBPA concentration exceeding the effective concentration was estimated as the time above half-maximal effective concentration (EC50 ) by using pharmacokinetic/pharmacodynamic modeling and simulation. Camostat mesylate was safe and tolerated at all dosages. Compared with the fasted state, the exposure of GBPA after a meal and 30 min before a meal was significantly lower; however, no significant difference was observed at 1 h before a meal. The time above EC50 was 11.5 h when camostat mesylate 600 mg was administered 4 times daily in the fasted state or 1 h before a meal. Based on the results of this phase I study, we are currently conducting a phase III study.

Perfect Discrimination in Approximate Quantum Theory of General Probabilistic Theories.

As a modern approach for the foundation of quantum theory, existing studies of general probabilistic theories gave various models of states and measurements that are quite different from quantum theory. In this Letter, to seek a more realistic situation, we investigate models approximately close to quantum theory. We define larger measurement classes that are smoothly connected with the class of POVMs via a parameter, and investigate the performance of perfect discrimination. As a result, we give a sufficient condition of perfect discrimination, which shows a significant improvement beyond the class of POVMs.

Ultrafast saturable absorption of large-diameter single-walled carbon nanotubes for passive mode locking in the mid-infrared.

We study the saturable absorption properties of single-walled carbon nanotubes (SWCNTs) with a large diameter of 2.2 nm and the corresponding exciton resonance at a wavelength of 2.4 µm. At resonant excitation, a large modulation depth of approximately 30 % and a small saturation fluence of a few tens of µJ/cm2 are evaluated. The temporal response is characterized by an instantaneous rise and a subpicosecond recovery. We also utilize the SWCNTs to realize sub-50 fs, self-start mode locking in a Cr:ZnS laser, revealing that the film thickness is an important parameter that affects the possible pulse energy and duration. The results prove that semiconductor SWCNTs with tailored diameters exceeding 2 nm are useful for passive mode locking in the mid-infrared range.

Non-catalytic heteroepitaxial growth of aligned, large-sized hexagonal boron nitride single-crystals on graphite.

Although van der Waals heterostructures composed of graphene and hexagonal boron nitride (h-BN) have attracted wide interest, it is still challenging to prepare them with high quality and controllability. Since contamination induced by transfer cannot be avoided in the case of growth on a metal catalyst, the non-catalytic growth of graphene and h-BN is highly desired. However, unlike graphene, few studies have reported the non-catalytic growth of h-BN, and the lack of controllability in terms of crystal orientation and nucleation density, and size of h-BN has hindered the practical applications of the heterostructures. In this work, we demonstrate the heteroepitaxial growth of aligned monolayer h-BN single-crystals on exfoliated graphite by chemical vapour deposition (CVD) without a metal catalyst. Triangular shaped domains were aligned with each other, which suggests the epitaxy between h-BN and the underlying graphite. Characterisation by Raman spectroscopy, Auger electron spectroscopy, and X-ray photoelectron spectroscopy also confirmed that the h-BN/graphite samples were of high quality. A growth kinetics study over different temperatures indicated an increase in the growth rate at high temperature. Control of nucleation density was realised by changing the hydrogen pressure during CVD or by the heating temperature in air before CVD. Under the optimised growth conditions, the edge length of h-BN single-crystals grew to ∼1 µm, which is the largest size to date for non-catalytic growth. These results will help to obtain structure-controlled, large-area, and impurity-free heterostructures based on h-BN and graphene.

One-dimensional van der Waals heterostructures.

We present the experimental synthesis of one-dimensional (1D) van der Waals heterostructures, a class of materials where different atomic layers are coaxially stacked. We demonstrate the growth of single-crystal layers of hexagonal boron nitride (BN) and molybdenum disulfide (MoS2) crystals on single-walled carbon nanotubes (SWCNTs). For the latter, larger-diameter nanotubes that overcome strain effect were more readily synthesized. We also report a 5-nanometer-diameter heterostructure consisting of an inner SWCNT, a middle three-layer BN nanotube, and an outer MoS2 nanotube. Electron diffraction verifies that all shells in the heterostructures are single crystals. This work suggests that all of the materials in the current 2D library could be rolled into their 1D counterparts and a plethora of function-designable 1D heterostructures could be realized.

Self-starting mode-locked Cr:ZnS laser using single-walled carbon nanotubes with resonant absorption at 2.4 µm.

We develop a mode-locked Cr:ZnS polycrystalline laser using single-walled carbon nanotubes (SWCNTs) that have resonant absorption at the wavelength of 2.4 µm. The laser generates ultrashort pulses of 49 fs duration, a 2.4 µm center wavelength, and a 9.2 THz (176 nm) spectral span at a repetition rate of 76 MHz. We also confirm self-starting of the mode-locked operation. SWCNTs, if appropriately controlled in terms of their diameters, prove to be useful as ultrafast saturable absorbers in the mid-infrared region.

Significant Dimension Reduction of 3D Brain MRI using 3D Convolutional Autoencoders.

Content-based image retrieval (CBIR) is a technology designed to retrieve images from a database based on visual features. While the CBIR is highly desired, it has not been applied to clinical neuroradiology, because clinically relevant neuroradiological features are swamped by a huge number of noisy and unrelated voxel information. Thus, effective dimension reduction is the key to successful CBIR. We propose a novel dimensional compression method based on 3D convolutional autoencoders (3D-CAE), which was applied to the ADNI2 3D brain MRI dataset. Our method succeeded in compressing 5 million voxel information to only 150 dimensions, while preserving clinically relevant neuroradiological features. The RMSE per voxel was as low as 8.4%, suggesting a promise of our method toward the application to the CBIR.

Efficacy and safety of tranexamic acid as an emetic in dogs.

OBJECTIVE: To determine dose dependency of tranexamic acid-induced emesis and the time course of the antifibrinolytic potency of tranexamic acid in dogs. ANIMALS: 10 Beagles. PROCEDURES: In a dose-escalating experiment, ascending doses of tranexamic acid (10, 20, and 30 mg/kg, IV) were administered at 5-minute intervals until vomiting was observed. In a separate single-dose experiment, ascending doses of tranexamic acid (20, 30, 40, and 50 mg/kg, IV) were administered at 1-week intervals until vomiting was observed. Time to onset of vomiting and number of vomiting episodes were measured in both experiments. In a coagulation experiment, a single 50 mg/kg bolus of tranexamic acid was administered, and blood was obtained 1 hour before and 20 minutes, 3 hours, and 24 hours after administration. Antifibrinolytic potency of tranexamic acid was evaluated by use of a modified rotational thromboelastography method. RESULTS: Tranexamic acid induced vomiting in a dose-dependent manner. Vomiting frequency was ≤ 2 episodes, and vomiting concluded ≤ 250 seconds after administration. Antifibrinolytic potency of tranexamic acid was significantly higher at 20 minutes following administration, but not different by 24 hours, when compared with the potency measured before administration. No adverse effects were observed in any experiment. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of tranexamic acid induced emesis in a dose-dependent manner. The antifibrinolytic potency of tranexamic acid decreased in a time-dependent manner and was resolved ≤ 24 hours after administration. Further studies are warranted to investigate the emetic and other adverse effects of tranexamic acid in dogs of various breeds and ages.