Swept-Source-Based Chromatic Confocal Microscopy.

Chromatic confocal microscopy (CCM) has been intensively developed because it can exhibit effective focal position scanning based on the axial chromatic aberration of broadband light reflected from a target. To improve the imaging speed of three-dimensional (3D) surface profiling, we have proposed the novel concept of swept-source-based CCM (SS-CCM) and investigated the usefulness of the corresponding imaging system. Compared to conventional CCM based on a broadband light source and a spectrometer, a swept-source in the proposed SS-CCM generates light with a narrower linewidth for higher intensity, and a single photodetector employed in the system exhibits a fast and sensitive response by immediately obtaining spectrally encoded depth from a chromatic dispersive lens array. Results of the experiments conducted to test the proposed SS-CCM system indicate that the system exhibits an axial chromatic focal distance range of approximately 360 µm for the 770-820 nm swept wavelength range. Moreover, high-speed surface profiling images of a cover glass and coin were successfully obtained with a short measurement time of 5 ms at a single position.

Non-destructive characterization of rare-earth-doped optical fiber preforms.

We present a non-destructive optical technique for rare-earth-doped optical fiber preform inspection, which combines luminescence spectroscopy measurements, analyzed through an optical tomography technique, and ray-deflection measurements for calculating the refractive-index profile (RIP) of the sample. We demonstrate the technique on an optical fiber preform sample with a Yb3+-doped aluminosilicate core. The spatial distribution of the photoluminescence signals originating from Yb3+-single ions and from Yb3+-Yb3+ cluster sites were obtained inside the core. By modifying the characterization system, we were able to concurrently evaluate the RIP of the core and, thus, establish with good accuracy the dopant distribution within the core region. This technique will be useful for quality evaluation and optimization of optical fiber preforms.

Crystal Structure Analysis of the First Discovered Stability-Enhanced Solid State of Tenofovir Disoproxil Free Base Using Single Crystal X-ray Diffraction.

Tenofovir disoproxil (TD), an anti-virus drug, is currently marketed under its most stable form, Form-I of Tenofovir disoproxil fumarate (TDF). However, studies regarding the properties of TD free base crystal as a promising drug as well as its crystal structure have not yet been reported. This assumption was made because TD free base is not directly produced in a solid form during the manufacturing process. TD free base is first obtained in an oil form, and is then synthesized into TDF crystal. In this regard, the present study was conducted to investigate both the potentiality of TD free base to be an active pharmaceutical ingredient (API) and its crystal structure. Here, TD free base solid was produced by means of drowning-out crystallization. Next, single crystal X-ray diffraction (SXD) was employed to determine the crystal structure. Powder X-ray diffraction (PXRD) and a differential scanning calorimetry (DSC) analysis were performed to evaluate the crystal's properties. Furthermore, experiments were carried out at 15%, 35%, 55%, 75%, and 95% relative humidity (RH) for 12 h using a hygroscopic tester to determine and to compare the hygroscopicity and stability of TD free base with TDF crystal. Additionally, experiments were conducted under accelerated (40 °C, RH 75%) and stress storage (60 °C, RH 75%) conditions for 30 days to investigate the changes in purity and the formation of dimer. In this work, we report that TD free base possesses lower hygroscopicity, and thus does not generate dimer impurity from hydrolysis. Primarily, this is attributed to the fact that TD free base is not an easily ionized salt but comprises neutral hydrophobic molecules. According to the structural properties, the improved hygroscopic property of the TD free base crystal was due to the decrease of crystal polarity owing to the intermolecular H-bonds present in TD free base rings. In addition, the solubility investigation study carried out in aqueous solution and at gastrointestinal pH revealed a similarity in TDF and TD free base solubility under the mentioned conditions. Accordingly, we could confirm the potentiality of TD free base as an active pharmaceutical ingredient.

Synthesis and biological evaluation of picolinamides as potent inhibitors of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1).

Synthesis of a series of 6-substituted picolinamide derivatives and their inhibitory activities against 11ß-hydroxysteroid dehydrogenase type 1 are described. Optimization of the initial hit compound, N-cyclohexyl-6-(piperidin-1-yl)picolinamide (1) from high throughput screening of in-house library resulted in the discovery of the highly potent and metabolically stable compound 25, which was efficacious in a mouse ex vivo pharmacodynamic model and reduced the fasting blood glucose and insulin levels in a HF/STZ mouse model after oral dosing.

Synthesis and optimization of picolinamide derivatives as a novel class of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors.

The synthesis and structure-activity relationship of a series of 6-substituted picolinamide inhibitors of 11ß-hydroxysteroid dehydrogenase type 1 are described. The optimization of the left-hand side of lead compound 1 resulted in the discovery of the highly potent, selective, and orally available inhibitor 24, which demonstrated an excellent activity in a mouse ex vivo pharmacodynamic model. Moreover, compound 24 reduced the blood glucose and improved the lipid profiles in ob/ob mice after oral administration.

Robust single-mode all-solid multi-trench fiber with large effective mode area.

We experimentally demonstrate all-solid 30 and 90 µm core diameter multi-trench fibers. Measurements ensure an effective single-mode operation over a wide range of bend radius in the case of 30 µm core fiber, making it suitable for applications like beam delivery and compact fiber lasers. On the other hand, a 90 µm core fiber ensures an effective single-mode operation and shows good potential for rod-type fiber laser applications. Both fibers were fabricated by the conventional modified chemical vapor deposition process in conjunction with the rod-in-tube technique, hence making them suitable for mass production.

Scalable Parallel Algorithm for Graph Neural Network Interatomic Potentials in Molecular Dynamics Simulations.

Message-passing graph neural network interatomic potentials (GNN-IPs), particularly those with equivariant representations such as NequIP, are attracting significant attention due to their data efficiency and high accuracy. However, parallelizing GNN-IPs poses challenges because multiple message-passing layers complicate data communication within the spatial decomposition method, which is preferred by many molecular dynamics (MD) packages. In this article, we propose an efficient parallelization scheme compatible with GNN-IPs and develop a package, SevenNet (Scalable EquiVariance-Enabled Neural NETwork), based on the NequIP architecture. For MD simulations, SevenNet interfaces with the LAMMPS package. Through benchmark tests on a 32-GPU cluster with examples of SiO2, SevenNet achieves over 80% parallel efficiency in weak-scaling scenarios and exhibits nearly ideal strong-scaling performance as long as GPUs are fully utilized. However, the strong-scaling performance significantly declines with suboptimal GPU utilization, particularly affecting parallel efficiency in cases involving lightweight models or simulations with small numbers of atoms. We also pretrain SevenNet with a vast data set from the Materials Project (dubbed "SevenNet-0") and assess its performance on generating amorphous Si3N4 containing more than 100,000 atoms. By developing scalable GNN-IPs, this work aims to bridge the gap between advanced machine-learning models and large-scale MD simulations, offering researchers a powerful tool to explore complex material systems with high accuracy and efficiency.

Development of a Customized Endoscopic Dual-Diffusing Optical Fiber Probe for Pancreatic Cancer Therapy: Toward Clinical Use.

Objective: We developed a dual-diffusing optical fiber probe (DDOFP), capable of uniformly illuminating the anatomical structure of pancreatic duct for photodynamic therapy (PDT) of pancreatic cancer in clinical settings. Background: Optical fiber presents a unique route for pancreatic PDT by enabling access to the pancreatic duct. For effective pancreatic PDT, the optical fiber should produce a uniform illumination covering of the pancreatic duct, while maintaining its transmission property under thermomechanical stresses in surgical environments. Methods: The transmission profiles of DDOFP were measured using a charge-coupled device (CCD) camera at two directions: front-spherical and side-cylindrical areas of the optical fiber. We simulated the change in transmission property by curved tube structures using optically transparent phantom. DDOFP was integrated with 19-gauge needle catheter that is commercially used as an optical guide to treat pancreatic cancer. The temperature of DDOFP was measured at the end face using a thermistor probe in the bovine tissue, while delivering laser energy of over 200 and 500 J. Results: DDOFP was customized to secure the inner diameter of the 19-gauge needle catheter of 686 µm to be integrated as a clinical device. The round ball lens fiber tip minimized the back-burn effect caused by blood carbonization during surgery and induced front-spherical diffusion. DDOFP produced uniform light illumination with intensity difference of <10%. When DDOFP was bent with a small curvature <15 mm, the transmission intensity was consistent. Under high-power laser transmission, DDOFP was found to be robust to cracking or deformation. Conclusions: DDOFP was customized for pancreatic PDT with superior thermomechanical property and uniform light illumination at both the front-spherical and side-cylindrical areas. This is the smallest clinically available optical fiber per our knowledge and officially approved by the Korea Food and Drug Administration (item approval number: 17-516). DDOFP can contribute immensely toward the efficient delivery of pancreatic PDT and photothermal therapy.

Anomalous Photocurrent Reversal Due to Hole Traps in AlGaN-Based Deep-Ultraviolet Light-Emitting Diodes.

The trap states and defects near the active region in deep-ultraviolet (DUV) light-emitting diodes (LED) were investigated through wavelength-dependent photocurrent spectroscopy. We observed anomalous photocurrent reversal and its temporal recovery in AlGaN-based DUV LEDs as the wavelength of illuminating light varied from DUV to visible. The wavelength-dependent photocurrent measurements were performed on 265 nm-emitting DUV LEDs under zero-bias conditions. Sharp near-band-edge (~265 nm) absorption was observed in addition to broad (300-800 nm) visible-range absorption peaks in the photocurrent spectrum, while the current direction of these two peaks were opposite to each other. In addition, the current direction of the photocurrent in the visible wavelength range was reversed when a certain forward bias was applied. This bias-induced current reversal displayed a slow recovery time (~6 h) when the applied forward voltage was removed. Furthermore, the recovery time showed strong temperature dependency and was faster as the sample temperature increased. This result can be consistently explained by the presence of hole traps at the electron-blocking layer and the band bending caused by piezoelectric polarization fields. The activation energy of the defect state was calculated to be 279 meV using the temperature dependency of the recovery time.

The reversible fourth-generation EGFR tyrosine kinase inhibitor OBX02-011 overcomes C797S-mediated resistance in lung cancer.

Osimertinib is an irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02-011, a reversible fourth-generation EGFR TKI that overcomes the EGFR C797S mutation. Compared to approved EGFR TKIs, OBX02-011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. Additionally, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02-011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02-011 may be a promising new EGFR TKI to overcome C797S-mediated resistance in NSCLC.