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Ethnopharmacological relevance Yongdamsagan-tang, a traditional herbal formula, is used widely for the treatment of inflammatory and viral diseases. However, the safety of Yongdamsagan-tang has not been established. Aim of the study To evaluate the subacute toxicity of Yongdamsagan-tang water extract (YSTE) in Crl:CD Sprague Dawley rats. Materials and methods We evaluated the subacute toxicity of YSTE in male and female Crl:CD Sprague Dawley rats (n = 5 per group). Rats were treated with YSTE at doses of 0, 1000, 2000 and 5000 mg/kg administered once a day by oral gavage for 4 weeks. Results There were no significant changes in mortality, body weight, food intake, serum biochemistry, or results of hematology and urinalysis after YSTE administration. However, all rats treated with 5000 mg/kg/day YSTE exhibited excessive salivation and discolored urine. Necropsy findings showed discoloration in the liver of both male (n = 1) and female (n = 3) rats treated with 5000 mg/kg/day YSTE, and an increase in the relative weights of kidney and liver was also found in male rats treated with 5000 mg/kg/day. In addition, decreases in serum creatinine, total bilirubin, alanine transaminase, and alkaline phosphatase were observed in male rats treated with 2000 or 5000 mg/kg/day YSTE. Conclusions Abnormalities in some rats are considered to be independent of YSTE toxicity. Therefore, the results suggest that oral administration of YSTE in rats for 4 weeks is safe at doses of up to 5000 mg/kg/day.

Cortisol is a well-known endogenous glucocorticoid that serves as a stress indicator. It is normally released under stressful condition to warn about imminent danger and thus is critical for survival of the species. However, it is unclear how cortisol relates to cognitive process under physiological condition in high-order primates such as non-human primates (NHP). Here, we report that a slight but significant increase in blood cortisol level by mild stress is positively correlated with the cognitive function in cynomolgus monkey. We stimulated 3 groups of monkeys by viewing consecutive series of pictures of monkeys, pictures of humans, or animation still pictures. We first found that the blood cortisol level was significantly higher during the stimulation session and returned to normal after stimulation session. Among the three types of pictures, the monkeys which were stimulated with monkey pictures showed the most significant increase in cortisol level during stimulation. Furthermore, the monkeys showed significantly enhanced manipulation, suggesting that cortisol affected cognitive processes. Overall, our study demonstrates that visual stimulation both increases blood cortisol and enhances manipulating behavior. Therefore, unlike the common notion that cortisol is a stress indicator, our data supports that a mild increase of cortisol enhances cognition in NHP.

Na x Ca y CoO 2 (0.45 ≤ x ≤ 0.64, 0.02 ≤ y ≤ 0.10) is synthesized via a solid-state method and examined as a cathode material to improve the cyclability of sodium ion batteries (SIBs). The substitution of one Ca 2+ for two Na + does not alter the P2-phase of undoped Na 0.73 CoO 2 , accompanying the continuous contraction of the unit cell volume with Ca-doping. The existence of Ca 2+ in the prismatic sites between CoO 6 slabs also affects the phase transition behaviors during charge–discharge (C–D). The suppression of Na + -vacancy ordering, ascribed to the immobility of Ca 2+ in Na x Ca y CoO 2 , leads to continuous changes of the cell voltages with no abrupt voltage drops during C–D. The reduced cell dimension and the mitigation of distinctiveness between biphasic and solid-solution domains during C-D improve the cyclability of Na x Ca y CoO 2 in SIBs. As an example, the negligible capacity fading in Na 0.60 Ca 0.07 CoO 2 during 60 cycles (0.07 mAh g −1 cycle −1 ) is contrasted with a substantial decrease in the reversible capacity of Na 0.73 CoO 2 (0.56 mAh g −1 cycle −1 ). Furthermore, a slower Na + diffusion of Na x Ca y CoO 2 in Na + -vacancy ordering regions, is sufficiently offset by a more rapid diffusion in all the other regions, which results in an improved rate performance. The platform presented here (multi-valent cation substitution for Na + ) could be utilized in other layered cathode materials to improve the electrochemical performance of SIBs.

Here, we propose a novel strategy to prepare dense stacks composed of alternating CoO and graphene layers for an anode in lithium ion batteries (LIBs), which contributes to enhanced stability and relatively large reversible capacity. This is accomplished by spontaneously pre-aligning negatively charged CoO-anchored graphene oxide (CG) and positively charged amine-functionalized graphene (GN) in an acidic medium, followed by thermal reduction. The performance of this product is contrasted with that of CG prepared under the identical conditions without the addition of GN, in which CoO nanoparticles are sandwiched between relatively loose and randomly oriented graphene stacks. For example, the composite delivers a capacity greater than 800 mAh g −1 with a fading rate of 0.04 mAh g −1 cycle −1 during 1000 charge/discharge (C/D) cycles at 1.0 A g −1 , in contrast to ca. 400 mAh g −1 and 0.24 mAh g −1 cycle −1 for thermally reduced CG without the addition of GN. The origin of the superior electrochemical performance in the dense stacks is ascribed to the enhanced reversibility of a conversion reaction, which in turn contributes to a persistent formation/dissolution of gel-like polymer films (i.e., stable pseudo-capacitance). Experimental evidences that substantiate the aforementioned behaviors (improved reversibility for both processes) are presented.

Oligopyrene (OPr, 3–4 pyrene units) is chemically synthesized and used as a high-voltage organic cathode for sodium ion batteries (SIBs). OPr shows anion-dominant transport behaviors during redox-switching in NaClO4 electrolytes, indicating that, when implemented in SIBs, OPr can reversibly incorporate/release perchlorate anions for charge-balance. A composite film, in which OPr maintains a crystalline phase with a layered structure, shows a sloping charge–discharge (C–D) curve (discharge capacity = 42.5 mAh g−1 and average voltage = 2.9 V vs. Na/Na+ at 20 mA g−1), implying a large overpotential due to slow ClO4− diffusion through the crystalline phase. In contrast, a composite film containing amorphous OPr exhibits substantially reduced overpotential with a plateau potential at 3.5 V during discharge. An initial reversible capacity of 121.0 mAh g−1, which is close to one-electron transfer per pyrene unit, is decreased to 95.8 mAh g−1 during the first 10 C–D cycles, but is subsequently stabilized with a decreasing rate of 0.30 mAh g−1 per C–D cycle. The energy density of amorphous OPr (423 Wh kg−1 for the 1st discharge) is so large that it exceeds those of most inorganic-based cathode materials that have been reported thus far.

Ethnopharmacological relevance Gyejibokryeong-hwan is a traditional herbal medicine and is reported to have various pharmacological actions. Despite many reports of previous studies, there is limited scientific evidence concerning its safety and few drug-metabolism profiles to support the continued therapeutic application of Gyejibokryeong-hwan. Aim of the study The purpose of the present study was to investigate the acute and subacute toxicity profile of a Gyejibokryeong-hwan water extract (GBHW) in vivo, and its effects on the activities of drug-metabolizing enzymes in vitro. Materials and methods Acute and subacute toxicity was evaluated by giving GBHW to rats. In a study of acute toxicity, the rats were given GBHW by single oral gavage administration at 0 and 5000 mg/kg. In a study of subacute toxicity, rats were given GBHW by oral gavage at 0, 1000, 2000, and 5000 mg/kg/day daily for 28 days. The activities of the major human microsomal cytochrome P450 (CYP450) and UDP-glucuronosyltransferase (UGT) isozymes were investigated using fluorescence- and luminescence-based enzyme assays in vitro, respectively. Results GBHW did not cause any mortality in the study of acute toxicity. In the study of subacute toxicity, GBHW at more than 2000 mg/kg/day was observed with minor changes in the absolute and relative organ weight, hematology, serum biochemistry and urinalysis parameters in rats of either sex. However, these changes were not considered to be important toxicologically. GBHW moderately inhibited the activities of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2E1, CYP3A4, and UGT1A1. Conclusions Our present data suggest that GBHW does not cause toxicologically important adverse events at doses up to 2000 mg/kg/day in the 4-week repeated dose toxicity study and provide valuable information concerning its potential to interact with conventional medicine.

ISIS 388626, a 2'-methoxyethyl (MOE)-modified antisense oligonucleotide (ASO) that targets human sodium glucose cotransporter 2 (SGLT2) mRNA, is in clinical trials for the management of diabetes. SGLT2 plays a pivotal role in renal glucose reabsorption, and inhibition of SGLT2 is anticipated to reduce hyperglycemia in diabetic subjects by increasing urinary glucose elimination. To selectively inhibit SGLT2 in the kidney, ISIS 388626 was designed as a "shortmer" ASO, consisting of only 12 nucleotides with two 2'-MOE-modified nucleotides at the termini. Mice and monkeys received up to 30 mg/kg/week ISIS 388626 via subcutaneous injection for 6 or 13 weeks. Dose-dependent decreases in renal SGLT2 mRNA expression were observed, which correlated with dose-related increases in glucosuria without concomitant hypoglycemia. There were no histologic changes in the kidney attributed to SGLT2 inhibition after 6 or 13 weeks of treatment. The remaining changes observed in these studies were typical of those produced in these species by the administration of oligonucleotides, correlated with high doses of ISIS 388626, and were unrelated to the inhibition of SGLT2 expression. The kidney contained the highest concentration of ISIS 388626, and dose-dependent basophilic granule accumulation in tubular epithelial cells of the kidney, which is evidence of oligonucleotide accumulation in these cells, was the only histologic change identified. No changes in kidney function were observed. These results revealed only readily reversible changes after the administration of ISIS 388626 and support the continued investigation of the safety and efficacy of ISIS 388626 in human trials.

W-doped LiW x Ni 0.5 Mn 1.5− x O 4 ( x = 0.00–0.10) are synthesized via a sol–gel method, and their electrochemical properties are investigated. During synthesis, W 4+ is converted to W 6+ , the amount of which significantly affects the charge–discharge behaviors of LiW x Ni 0.5 Mn 1.5− x O 4 . When limited to x ≤ 0.005, W-doping enhances the electrochemical activity of cathodes, leading to a greater discharge capacity and less capacity fading than LiNi 0.5 Mn 1.5 O 4 at high C -rates. This is interesting since lowering the average valence state of Mn ions by incorporating W 6+ can introduce structural instability, extending a 4 V plateau (Mn 3+/4+ ). The reasons for such behavior associated with W-doping are examined by electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and impedance spectroscopy. It is disclosed that the simultaneous increase in Li O bond length and decrease in transition metal-oxide bond length, while the unit cell volume is maintained almost invariant, provides LiW 0.005 Ni 0.5 Mn 1.495 O 4 with optimal high rate performance. When W-doping exceeds x = 0.01, 3 factors (intrinsically low electronic conductivity of W 6+ , the presence of tungsten oxide impurities, and an increase in the inter-metallic distance) aggravates electrochemical performance of LiW x Ni 0.5 Mn 1.5− x O 4 . The last factor also induces structural instability during repeated cycling because of the expansion of a unit cell volume.

KCrS2 is presented as a stable and high-rate layered material that can be used as a cathode in potassium-ion batteries. As far as it is known, KCrS2 is the only layered material with stoichiometric amounts of K+ , which enables coupling with a graphite anode for full-cell construction. Cr(III)/Cr(IV) redox in KCrS2 is also unique, because LiCrS2 and NaCrS2 are known to experience S2- /S22- redox. O3-KCrS2 is first charged to P3-K0.39 CrS2 and subsequently discharged to O'3-K0.8 CrS2 , delivering an initial discharge capacity of 71 mAh g-1 . The following charge/discharge (C/D) shows excellent reversibility between O'3-K0.8 CrS2 and P3-K0.39 CrS2 , retaining ≈90% of the initial capacity during 1000 continuous cycles. The rate performance is also noteworthy. A C/D rate increase of 100-fold (0.05 to 5 C) reduces the reversible capacity only by 39% (71 to 43 mAh g-1 ). The excellent cyclic stability and high rate performance are ascribed to the soft sulfide framework, which can effectively buffer the stress caused by K+ deinsertion/insertion. During the transformation between P3-K0.39 CrS2 and O'3-K0.8 CrS2 , the material resides mostly in the P3 phase, which minimizes the abrupt dimension change and allows facile K+ diffusion through spacious prismatic sites. Structural analysis and density functional theory calculations firmly support this reasoning.

C57BL/6N mice are inbred strains widely used in biomedical research. Hence, a large amount of basic data has been accumulated. However, in the field of histopathology, spontaneous data for relatively younger mice that are used more frequently are not yet abundant, in contrast to data for older mice and their neoplastic lesions. To acquire the essential background data required by various research and toxicological assessments, 120 mice of the C57BL/6N strain (10 and 13 weeks of age) were collected from two institutions (From Korea and Japan) and subjected to histopathological analyses of the major organs (liver, spleen, kidney, thymus, heart, testis, epididymis). The results showed significantly higher incidence of sperm granulomas in the epididymides (10–56%) of these mice, compared with that in other strains or species of lab animals. Upon closer inspection, oligospermia/clear cell hyperplasia, cellular debris, and tubular vacuolation were also observed in the epididymides with sperm granulomas. Moreover, diseased organs were significantly heavier than healthy ones. Immunohistochemical staining showed a significant increase in the chromatic figures of cysteine-dependent aspartate-directed proteases-3 (caspase-3) and cleaved-poly(ADP-ribose) polymerase (c-PARP), and damages to the tubule due to spontaneous apoptosis, which may have led to the sperms leaking out of the tubule, causing the granuloma. To conclude, spontaneous sperm granuloma can occur in 10- and 13-week-old C57BL/6N mice and may thus affect the results of various studies using these mice. Therefore, sperm granuloma in epididymis needs to be carefully considered as an important factor when design the study using C57BL/6N.

A collision avoidance algorithm for unmanned aerial vehicles (UAVs) based on the conventional proportional navigation (PN) guidance law is investigated. The proportional navigation guidance law being applied to a wide range of missile guidance problems is tailored to the collision avoidance of UAVs. This can be accomplished by guiding the relative velocity vector of the aircraft to a vector connecting the current aircraft position to the safety boundary of the target aircraft. Stability of the proposed algorithm is also studied using the circle criterion. The stability condition can be established by choosing the navigation coefficient within a certain bound. The guidance law is extended to 3-dimensional maneuver problems. Inherent simplicity and robustness of the PN guidance law provides satisfactory collision avoidance performance with different initial conditions.

Active real-time THz imaging system (ARTIS) for non-destructive inspection (NDI), requires a powerful T-ray source capable of illuminating large inspection area at a time. A sub-THz gyrotron satisfying such a unique requirement is proven to be effective not only for NDI but also for bio-medical application such as enhanced regeneration of cells.

Collision avoidance for multiple aircraft can be stated as a problem of maintaining safe distance between aircraft in conflict. Optimal collision avoidance problem seeks to minimize the given cost function while simultaneously satisfying constraints. The cost function could be a function of time or control input. This paper addresses the trajectory time-optimization problem for collision avoidance of unmanned aerial vehicles(UAVs). The problem is difficult to handle in general due to the two-point boundary value problem subject to dynamic environments. Some simplifying algorithms are used for potential applications in on-line operation. Although under possibility of more complicated problems, a dynamic problem is transformed into a static one by prediction of the conflict time and some appropriate assumptions.

In this paper, we make a design study for a local oscillator system of the 100 GHz band cosmic radio receiving system. We use the YIG oscillator with digital driver which is the main oscillator. This oscillator has a good frequency and phase stability at some temperature variation, and the easy computer aided control characteristics. This total system designed to two subsystem, first is the oscillator system include YIG oscillator, tripler, harmonic mixer and triplexer etc., second is the PLL system to supply the precise and stable local oscillator frequency to mixer. The proposed local oscillator system in this paper can be used in a single or multi pixel receiver because this system can be lock the local oscillator frequency automatically using PC.

Up to date, a devotion to high energy density (ED) Li ion batteries (LIBs) has been carried out via rather one-by-one confirmation of a relationship between electrochemical properties and materials traits without a general, reliable, and comprehensive model. Therefore, although such a scrutinized investigation on a specific cathode material has elicited significant scientific findings, the sensitive dependence of electrochemical properties on crystallographic and elemental properties made the generalization of such findings difficult. Density functional theory (DFT) calculation could compensate for these shortcomings to some extent. However, DFT is also far from complete in understanding the overall trend of reported experimental data, indicating a necessity of a new systematic approach that can prospect a whole experimental data a quantum-leap innovation in material designs. In this work, we data-mine the cathode materials of LIBs through confirmatory factor analysis (CFA). Both layered and spinel structures are data-mined separately. By collecting accurate structural and electrochemical data of the both types, we prepared a systematic data set and utilized it in the CFA through principal component analysis (PCA) and a simple linear regression. The data sets that we adopt for CFA are huge in size, i.e., 19 X 40 for layered structure and 16 X 33 for spinel. The CFA reveals that, while the control of a few crystallographic parameters is critical for layered cathodes of high ED, some of intrinsic properties of constituent elements govern the ED in spinel structures. The CFA also disclose that the cyclability of the both is irrelevant to the parameters we selected, implying that the electrochemical conditions during C-D are crucial factors for the least capacity (Q) fading. The acquisition of these conceptual understandings with human cognition capability is practically impossible without a smart statistical approach like CFA.

This research is to estimate the toxicity of Atractylodis Rhizoma Alba (ARA) in F344 rats and to find a dose level for the 13 weeks toxicity study. A hot water extract of ARA (ARWE) was administered orally to F344 rats at dose levels of 0 (vehicle control), 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed to five male and five female F344 rats. According to the result, there were no ARWErelated adverse changes in mortality, body weights, food consumption, urinalysis, hematology, clinical chemistry, gross finding at necropsy, and organ weight examination. Salivation was observed in 3500 and 5000 mg/kg/day in male and female rats but it could not have found any relationship with ARWE administration. Based on our findings, ARWE may not cause toxicity in rats under the experimental conditions. Therefore, dose level of 5000 mg/kg/day as a highest treatment group in 13-week exposure study is recommended for further toxicity assessment.

Nonhuman primates are increasingly used in biomedical research since they are highly homologous to humans compared to other rodent animals. However, there is limited reliable reference data of the clinical pathology parameters in cynomolgus monkeys, and in particular, only some coagulation and urinalysis parameters have been reported. Here, we reported the reference data of clinical chemical, hematological, blood coagulation, and urinalysis parameters in cynomolgus monkeys. The role of sex differences was analyzed and several parameters (including hematocrit, hemoglobin, red blood cell, blood urea nitrogen, total bilirubin, alkaline phosphatase, creatinine kinase, gamma-glutamyl tranferase, and lactate dehydrogenase) significantly differed between male and female subjects. In addition, compared to previous study results, lactate dehydrogenase, creatinine kinase, and aspartate aminotransferase showed significant variation. Interstudy differences could be affected by several factors, including age, sex, geographic origin, presence/absence of anesthetics, fasting state, and the analytical methods used. Therefore, it is important to deliberate with the overall reference indices. In conclusion, the current study provides a comprehensive and updated reference data of the clinical pathology parameters in cynomolgus monkeys and provides improved assessment criteria for evaluating preclinical studies or biomedical research.

The effects of ketamine anesthesia on both hematological and serum biochemical variables were investigated in 19 male and 15 female cynomolgus monkeys. Blood samples were obtained from the cephalic vein within 30 minutes of an intramuscular injection of ketamine hydrochloride (10 mg/kg). Ketamine anesthesia caused a reduction in leukocyte counts and a significant reduction in lymphocytes percentages. Ketamine anesthesia also increased the serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine phosphokinase (CPK), but reduced the serum concentrations of glucose, inorganic phosphate, sodium and potassium. The alterations of hematological and serum biochemical values will be discussed. These alterations should be considered when designing studies for and interpreting data from cynomolgus monkeys.

NaNi0.5Mn0.5O2 (NNMO), which has a layered structure, is a promising cathode material for sodium ion batteries. The stack of Mn(Ni)O2 slabs in a layered structure of NaiNi0.5Mn0.5O2, are composed of edge-shared Mn(Ni)O6 octahedra, forming metal-occupied octahedral sites and empty tetrahedral sites. The octahedral sites in Na slabs are also occupied by Na+ ions, which are sandwiched by edge-sharing with Mn(Ni)O2 slabs. In this work, O3-CaxNa1-2x[Ni0.5Mn0.5]O2 (0 < x ≤ 0.1) was synthesized by incorporating Ca2+ into NaO6 layer of Na[Ni0.5Mn0.5]O2. Both the significant difference in ionic radii between Ca2+ (1.12Å) and Ni2+ (0.69Å) or Mn4+ (0.53 Å) and the reduction of Na+ content allowed the preparation of phase-pure and cation-mixing-free (i.e., absence of Ca2+ in transition metal oxide layers) CaxNa1-2x[Ni0.5Mn0.5]O2 up to x = 0.05. It was expected that, while no noticeable change was observed in a dimension of MnO6 octahedron, NaO6 octahedron continuously shrank as the increase of Ca2+ content. The latter effect was expected to prevent the structural degradation during repeated charge-discharge, eventually contributing to the improvement of capacity retention. Preliminary study indicated that, while pristine Na[Ni0.5Mn0.5]O2 showed a continuous decrease in discharge capacity, Ca0.05Na0.90[Ni0.5Mn0.5]O2 maintained a significant fraction of an initial capacity with a small capacity fading during 50 cycles. The excellent capacity retention of Ca2+-doped one is believed because the strong interaction of immobile Ca2+ with O2- helps restore of the initial O3 structure, which leads to the maintenance of distinctive phase transition steps on discharge profiles after repeated cycles in contrast to pristine one.

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Department of Radiation Oncology, *Asan Medical Center, University of Ulsan College of Medicine, Seoul Inha Univeristy Hospital, Incheon, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, College of Medicine, Gachon University Gil Hospital, Incheon,Hanyang University Hospital, Seoul, ¶ Soonchunhyang University Hospital, College of Medicine, Asan, **Department of Radiological Science, College of Health Science, Eulji University, Seongnam, Department of Radiation Oncology, College of Medicine, Kyung Hee University Medical Center, Suwon, Cheil General Hospital & Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Inje University Hospital, Seoul, Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul, Korea