Development of a Novel System for Mass Spectrometric Analysis of Cancer-Associated Fucosylation in Plasma α1-Acid Glycoprotein

Human plasma α1-acid glycoprotein (AGP) from cancer patients and healthy volunteers was purified by sequential application of ion-exchange columns, and N-linked glycans enzymatically released from AGP were labeled and applied to a mass spectrometer. Additionally, a novel software system for use in combination with a mass spectrometer to determine N-linked glycans in AGP was developed. A database with 607 glycans including 453 different glycan structures that were theoretically predicted to be present in AGP was prepared for designing the software called AGPAS. This AGPAS was applied to determine relative abundance of each glycan in the AGP molecules based on mass spectra. It was found that the relative abundance of fucosylated glycans in tri- and tetra-antennary structures (FUCAGP) was significantly higher in cancer patients as compared with the healthy group (P<0.001). Furthermore, extremely elevated levels of FUCAGP were found specifically in patients with a poor prognosis but not in patients with a good prognosis. In conclusion, the present software system allowed rapid determination of the primary structures of AGP glycans. The fucosylated glycans as novel tumor markers have clinical relevance in the diagnosis and assessment of cancer progression as well as patient prognosis

A diamond 14 MeV neutron energy spectrometer with high energy resolution

A self-standing single-crystal chemical vapor deposited diamond was obtained using lift-off method. It was fabricated into a radiation detector and response function measurements for 14 MeV neutrons were taken at the fusion neutronics source. 1.5% of high energy resolution was obtained by using the C-12(n, alpha)Be-9 reaction at an angle of 100 degrees with the deuteron beam line. The intrinsic energy resolution, excluding energy spreading caused by neutron scattering, slowing in the target and circuit noises was 0.79%, which was also the best resolution of the diamond detector ever reported

High-performance diamond radiation detectors produced by lift-off method

For stable semiconductor detector operation under harsh environments, an ideal single-crystal diamond without a charge trapping centre is required. For this study, a self-standing single-crystal CVD diamond was fabricated using a lift-off method. The reduction of charge trapping factors such as structural defects, point defects, and nitrogen impurities, was attempted using 0.2% of low-methane concentration growth and using a full metal seal chamber. A high-quality self-standing diamond with strong free-exciton recombination emission was obtained. Charge collection efficiencies were 100.1% for holes and 99.8% for electrons, provided that $\varepsilon_{\mathrm{diamond}}= 13.1\ \text{eV}$ and $\varepsilon_{\mathrm{Si}}=3.62\ \text{eV}$ . Energy resolutions were 0.38% for both holes and electrons. We produced a high-performance diamond radiation detector using the productive lift-off method

Biomechanical profiles of tracheal intubation: a mannequin-based study to make an objective assessment of clinical skills by expert anesthesiologists and novice residents

Abstract Background Tracheal intubation (TI) is a key medical skill used by anesthesiologists and critical care physicians in airway management in operating rooms and critical care units. An objective assessment of dexterity in TI procedures would greatly enhance the quality of medical training. This study aims to investigate whether any biomechanical parameters obtained by 3D-motion analysis of body movements during TI procedures can objectively distinguish expert anesthesiologists from novice residents. Methods Thirteen expert anesthesiologists and thirteen residents attempted TI procedures on an airway mannequin using a Macintosh laryngoscope. Motion capturing technology was utilized to digitally record movements during TI procedures. The skill with which experts and novices measured biomechanical parameters of body motions were comparatively examined. Results The two groups showed similar outcomes (success rates and mean time needed to complete the TI procedures) as well as similar mean absolute velocity values in all 21 body parts examined. However, the experts exhibited significantly lower mean absolute acceleration values at the head and the left hand than the residents. In addition, the mean-absolute-jerk measurement revealed that the experts commanded potentially smoother motions at the head and the left hand. The Receiver Operating Characteristic (ROC) curves analysis demonstrated that mean-absolute-acceleration and -jerk measurements provide excellent measures for discriminating between experts and novices. Conclusions Biomechanical parameter measurements could be used as a means to objectively assess dexterity in TI procedures. Compared with novice residents, expert anesthesiologists possess a better ability to control their body movements during TI procedures, displaying smoother motions at the selected body parts

α‑1‑<i>C</i>‑Butyl-1,4-dideoxy-1,4-imino‑l‑arabinitol as a Second-Generation Iminosugar-Based Oral α‑Glucosidase Inhibitor for Improving Postprandial Hyperglycemia

We report on the synthesis and the biological evaluation of a series of α-1-<i>C</i>-alkylated 1,4-dideoxy-1,4-imino-l-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross-coupling as key reactions. α-1-<i>C</i>-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC₅₀ values of 0.13, 4.7, and 0.032 μM, respectively. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis revealed that this compound differs from miglitol in that it does not influence oligosaccharide processing and the maturation of glycoproteins. A molecular docking study of maltase-glucoamylase suggested that the interaction modes and the orientations of α-1-<i>C</i>-butyl-LAB and miglitol are clearly different. Furthermore, α-1-<i>C</i>-butyl-LAB strongly suppressed postprandial hyperglycemia at an early phase, similar to miglitol in vivo. It is noteworthy that the effective dose was about 10-fold lower than that for miglitol. α-1-<i>C</i>-Butyl-LAB therefore represents a new class of promising compounds that can improve postprandial hyperglycemia