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Astroviruses (AstVs) have been detected in a wide range of animal species, including mammals and birds. Recently, a novel AstV associated with neurological symptoms has been detected in the brains of some mammals. Raccoon dog AstV has been reported recently in China. However, there have been no reports in South Korea. Therefore, the present study aimed to detect and genetically characterize AstVs in the intestine and brain tissues of 133 wild raccoon dogs collected in Korea between 2017 and 2019. Of the seven raccoon dogs, AstVs were detected in six intestinal tissues and four brain tissues. Analysis of the capsid protein amino acid sequences of raccoon dog AstVs detected in Korea revealed a high similarity to canine AstVs, suggesting possible interspecies transmission between raccoon dogs and dogs. Phylogenetic and capsid protein amino acid sequence analysis of raccoon dog AstVs detected in the brain the 17-148B strain belonging to the HMO clade and exhibiting conserved sequences found in neurotropic AstVs (NT-AstVs), indicating their potential as NT-AstVs. However, the pathogenicity and transmission routes of the raccoon dog AstV detected in Korea have not yet been elucidated, so further research and continued surveillance for AstV in wild raccoon dogs are needed.

Jun Soo Park,1 Min Seop Kim,1 Min Yeong Joung,1 Hyun Jin Park,1 Myoung-Jin Ho,1 Jun Hyuk Choi,1 Jae Hee Seo,1 Woo Heon Song,1 Young Wook Choi,2 Sangkil Lee,3 Yong Seok Choi,1 Myung Joo Kang1 1College of Pharmacy, Dankook University, Cheonan, Republic of Korea; 2College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 3College of Pharmacy, Keimyung University, Daegu, Republic of KoreaCorrespondence: Myung Joo Kang, College of Pharmacy, Dankook University, Dongnam-gu, Cheonan, 31116, Republic of Korea, Tel +82 41 550 1446, Fax +82 41 550 7899, Email kangmj@dankook.ac.krBackground: Montelukast (MTK), a representative leukotriene receptor antagonist, is currently being investigated as a potential candidate for treating Alzheimer’s disease. For potent and effective dosing in elderly patients, a parenteral prolonged delivery system is favored, with improved medication adherence with reduced dosage frequency.Purpose: This study aimed to design a nanocrystalline suspension (NS)-based MTK prolonged delivery system and evaluate its pharmacokinetics profile and local tolerability following subcutaneous administration.Methods: To decelerate the dissolution rate, the amorphous MTK raw material was transformed into a crystalline state using a solvent-mediated transformation method and subsequently formulated into NS using a bead-milling technique. The MTK NSs were characterized by morphology, particle size, crystallinity, and in vitro dissolution profiles. The pharmacokinetic profile and local tolerability at the injection site following subcutaneous injection of MTK suspension were evaluated in rats.Results: Microscopic and physical characterization revealed that the amorphous MTK powder was lucratively transformed into a crystalline form in acidic media (pH 4). MTK crystalline suspensions with different diameters (200 nm, 500 nm, and 3 μm) were uniformly prepared using bead-milling technology, employing polysorbate 80 as suspending agent. Prepared crystalline suspensions exhibited analogous crystallinity (melting point, 150°C) and size-dependent in vitro dissolution profiles. MTK NSs with particle sizes of 200 nm and 500 nm provided a protracted pharmacokinetic profile for up to 4 weeks in rats, with a higher maximum drug concentration in plasma than the 3 μm-sized injectable suspensions. Histopathological examination revealed that MTK NS caused chronic granulomatous inflammation at the injection site, which resolved after 4 weeks.Conclusion: The MTK parenteral NS delivery system is expected to be a valuable tool for treating Alzheimer’s disease with extended dose intervals.Graphical Abstract: Keywords: montelukast, parenteral prolonged release delivery, crystallinity, nanocrystalline suspension, bead-milling, pharmacokinetics, local tolerability

Eun A Kim, Jun Soo Park, Min Seop Kim, Min Young Jeong, Hyun Jin Park, Jun Hyuk Choi, Jae Hee Seo, Yong Seok Choi, Myung Joo Kang College of Pharmacy, Dankook University, Cheonan, Chungnam, 330-714, KoreaCorrespondence: Myung Joo KangCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, 330-714, KoreaTel +82 41 550 1446Fax +82 41 550 7899. Email kangmj@dankook.ac.krBackground: The titrated extract of Centella asiatica (CA) has received much attention as a cosmeceutical ingredient owing to its anti-wrinkle effect. However, due to the low solubility and high molecular weight of pharmacologically active constituents, including asiatic acid (AA), madecassic acid (MA), and asiaticoside (AS), it is challenging to fabricate high-payload topical preparations of CA with satisfactory skin absorption profiles.Purpose: This study aimed to design a high-payload topical preparation of CA using nanocrystallization technique and to evaluate its skin absorption profile and local tolerability.Methods: High-payload nanocrystal suspensions (NSs) were prepared using lab-scale bead-milling technology, by adjusting the type and amount of suspending agent, CA content, type of vehicle, and milling speed. CA-loaded NSs were characterized in terms of morphology, particle size, crystallinity, and in vitro dissolution pattern. Skin absorption of CA nanocrystals was evaluated using a vertical Franz diffusion cell mounted with porcine skin. In vivo skin irritation following topical application of high-payload NS was assessed in normal rats.Results: The optimized NS system, composed of 10% (w/v) CA, 0.5% polyvinylpyrrolidone (PVP) K30 as steric stabilizer, and 89.5% of distilled water, was characterized as follows: spherical or elliptical in shape, 200 nm in size, with low crystallinity. The in vitro dissolution of AA or MA from NSs was markedly faster compared to raw material, under sink condition. Penetration of AA, MA, and AS in the porcine skin was markedly elevated using the high-payload NS formula, providing 5-, 4-, and 4.5-fold higher accumulation in skin layer, compared to that of the marketed cream formula (CA 1%, Madeca cream). Moreover, topical application of high-payload NS was tolerable, showing neither erythema nor oedema in normal rats.Conclusion: The novel NS system is expected to be a virtuous approach for offering a better skin absorption of CA, without using an excess quantity of solubilizers.Keywords: Centella asiatica, asiatic acid, madecassic acid, asiaticoside, nanocrystal suspension, bead-milling, dissolution, skin absorption, skin irritation

Bats are natural reservoirs for potential zoonotic viruses. In this study, next-generation sequencing was performed to obtain entire genome sequences of picornavirus from a picornavirus-positive bat feces sample (16BF77) and to explore novel viruses in a pooled bat sample (16BP) from samples collected in South Korea, 2016. Fourteen mammalian viral sequences were identified from 16BF77 and 29 from 16BP, and verified by RT-PCR. The most abundant virus in 16BF77 was picornavirus. Highly variable picornavirus sequences encoding 3Dpol were classified into genera Kobuvirus, Shanbavirus, and an unassigned group within the family Picornaviridae. Amino acid differences between these partial 3Dpol sequences were ≥ 65.7%. Results showed that one bat was co-infected by picornaviruses of more than two genera. Retrovirus, coronavirus, and rotavirus A sequences also were found in the BP sample. The retrovirus and coronavirus genomes were identified in nine and eight bats, respectively. Korean bat retroviruses and coronavirus demonstrated strong genetic relationships with a Chinese bat retrovirus (RfRV) and coronavirus (HKU5-1), respectively. A co-infection was identified in one bat with a retrovirus and a coronavirus. Our results indicate that Korean bats were multiply infected by several mammal viruses.

Background Cordyceps militaris (L.) Fr. (C. militaris) exhibits pharmacological activities, including antitumor properties, through the regulation of the nuclear factor kappa B (NF-κB) signaling. Tumor Necrosis Factor (TNF) and TNF-α modulates cell survival and apoptosis through NF- κB signaling. However, the mechanism underlying its mode of action on the NF-κB pathway is unclear. Methods Here, we analyzed the effect of C. militaris extract (CME) on the proliferation of ovarian cancer cells by confirming viability, morphological changes, migration assay. Additionally, CME induced apoptosis was determined by apoptosis assay and apoptotic body formation under TEM. The mechanisms of CME were determined through microarray, immunoblotting and immunocytochemistry. Results CME reduced the viability of cells in a dose-dependent manner and induced morphological changes. We confirmed the decrease in the migration activity of SKOV-3 cells after treatment with CME and the consequent induction of apoptosis. Immunoblotting results showed that the CME-mediated upregulation of tumor necrosis factor receptor 1 (TNFR1) expression induced apoptosis of SKOV-3 cells via the serial activation of caspases. Moreover, CME negatively modulated NF-κB activation via TNFR expression, suggestive of the activation of the extrinsic apoptotic pathway. The binding of TNF-α to TNFR results in the disassociation of IκB from NF-κB and the subsequent translocation of the active NF-κB to the nucleus. CME clearly suppressed NF-κB translocation induced by interleukin (IL-1β) from the cytosol into the nucleus. The decrease in the expression levels of B cell lymphoma (Bcl)-xL and Bcl-2 led to a marked increase in cell apoptosis. Conclusion These results suggest that C. militaris inhibited ovarian cancer cell proliferation, survival, and migration, possibly through the coordination between TNF-α/TNFR1 signaling and NF-κB activation. Taken together, our findings provide a new insight into a novel treatment strategy for ovarian cancer using C. militaris.

H7 low pathogenic avian influenza viruses (LPAIVs) can mutate into highly pathogenic avian influenza viruses (HPAIVs). In addition to avian species, H7 avian influenza viruses (AIVs) also infect humans. In this study, two AIVs, H7N9 (20X-20) and H7N7 (34X-2), isolated from the feces of wild birds in South Korea in 2021, were genetically analyzed. The HA cleavage site of the two H7 Korean viruses was confirmed to be ELPKGR/GLF, indicating they are LPAIVs. There were no amino acid substitutions at the receptor-binding site of the HA gene of two H7 Korean viruses compared to that of A/Anhui/1/2013 (H7N9), which prefer human receptors. In the phylogenetic tree analysis, the HA gene of the two H7 Korean viruses shared the highest nucleotide similarity with the Korean H7 subtype AIVs. In addition, the HA gene of the two H7 Korean viruses showed high nucleotide similarity to that of the A/Jiangsu/1/2018(H7N4) virus, which is a human influenza virus originating from avian influenza virus. Most internal genes (PB2, PB1, PA, NP, NA, M, and NS) of the two H7 Korean viruses belonged to the Eurasian lineage, except for the M gene of 34X-2. This result suggests that active reassortment occurred among AIVs. In pathogenicity studies of mice, the two H7 Korean viruses replicated in the lungs of mice. In addition, the body weight of mice infected with 34X-2 decreased 7 days post-infection (dpi) and inflammation was observed in the peribronchiolar and perivascular regions of the lungs of mice. These results suggest that mammals can be infected with the two H7 Korean AIVs. Our data showed that even low pathogenic H7 AIVs may infect mammals, including humans, as confirmed by the A/Jiangsu/1/2018(H7N4) virus. Therefore, continuous monitoring and pathogenicity assessment of AIVs, even of LPAIVs, are required.

Bats have been identified as a natural reservoir of several potentially zoonotic viruses, including Lyssavirus, Ebola virus, Marburg virus, Hendra virus, Nipah virus, as well as severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus (CoV). Here, we performed a molecular epidemiological investigation of South Korean bat viruses. Genetic comparative analysis was performed on the spike glycoprotein gene of the detected MERS-related CoVs. Among 1640 samples (348 oral swabs, 1199 faecal samples, 83 urine samples and 10 bat carcass) collected across 24 South Korean provinces during 2017-2019, CoV was detected in 82 samples (75 faeces and seven oral swab samples) from 11 provinces. Surveillance over the 3 years during which samples were collected revealed significantly higher CoV detection rates between spring and autumn, and a high detection rate in Vespertillionidae and Rhinolophidae bats. Our phylogenetic analysis shows that Korean bat CoVs are genetically diverse regardless of their spatiotemporal distribution and their host species, and that the discovered bat CoVs belong to various subgenera within the Alpha- and Betacoronavirus genera. Twenty detected MERS-related CoVs belonging to the genus Betacoronavirus were similar to the Ia io bat CoV NL140422 and NL13845 strains. A comprehensive genetic analysis of two Korean bat MERS-related CoV spike receptor binding domain (RBDs) (176 and 267 strains) showed that the 18 critical residues that are involved in interactions with the human DPP4 receptor are most similar to the NL13845 strain, which is known to not bind with hDPP4. A deeper analysis of the interfacing residues in the Korean bat MERS-related CoVs RBD-hDPP4 complexes showed that the Korean bat CoVs has fewer polar contacts than the NL13845 strain. Although further study will be needed, these results suggest that Korean bat MERS-related CoVs are unlikely to bind with hDPP4. Nevertheless, these findings highlight the need for continuous monitoring to identifying the origin of new infectious diseases, specifically mutant CoV.

Background The titrated extract of Centella asiatica (CA) has received much attention as a cosmeceutical ingredient owing to its anti-wrinkle effect. However, due to the low solubility and high molecular weight of pharmacologically active constituents, including asiatic acid (AA), madecassic acid (MA), and asiaticoside (AS), it is challenging to fabricate high-payload topical preparations of CA with satisfactory skin absorption profiles. Purpose This study aimed to design a high-payload topical preparation of CA using nanocrystallization technique and to evaluate its skin absorption profile and local tolerability. Methods High-payload nanocrystal suspensions (NSs) were prepared using lab-scale bead-milling technology, by adjusting the type and amount of suspending agent, CA content, type of vehicle, and milling speed. CA-loaded NSs were characterized in terms of morphology, particle size, crystallinity, and in vitro dissolution pattern. Skin absorption of CA nanocrystals was evaluated using a vertical Franz diffusion cell mounted with porcine skin. In vivo skin irritation following topical application of high-payload NS was assessed in normal rats. Results The optimized NS system, composed of 10% (w/v) CA, 0.5% polyvinylpyrrolidone (PVP) K30 as steric stabilizer, and 89.5% of distilled water, was characterized as follows: spherical or elliptical in shape, 200 nm in size, with low crystallinity. The in vitro dissolution of AA or MA from NSs was markedly faster compared to raw material, under sink condition. Penetration of AA, MA, and AS in the porcine skin was markedly elevated using the high-payload NS formula, providing 5-, 4-, and 4.5-fold higher accumulation in skin layer, compared to that of the marketed cream formula (CA 1%, Madeca cream). Moreover, topical application of high-payload NS was tolerable, showing neither erythema nor oedema in normal rats. Conclusion The novel NS system is expected to be a virtuous approach for offering a better skin absorption of CA, without using an excess quantity of solubilizers.

Oral montelukast (MTK) is prescribed to treat asthma or rhinitis, and is clinically investigated as new medication in the treatment of Alzheimer's dementia. Herein, in order to better patient's compliance, microsuspensions (MSs)-based oral liquid preparations of montelukast (MTK) were formulated with polymeric suspending agents including hypromellose (HPMC), and those drug-polymer interaction, physicochemical stability, dissolution, and in vivo pharmacokinetic profile was evaluated. When amorphous MTK particle was suspended in aqueous vehicle, it was readily converted into crystalline form and grown into aggregates, drastically lowering dissolution rate. However, the addition of HPMC polymer markedly suppressed the crystal growth, providing both improved drug stability and profound dissolution profile. Raman spectrometry denoted the inter-molecular hydrogen boding between MTK particle and HPMC polymer. The crystal growth or dissolution profile of MSs was markedly affected by pharmaceutical additives (sucrose or simethicone) in the preparations or storage temperature. The optimized HPMC-based MS exhibited over 80% higher bioavailability, compared to marketed granule (Singulair®) in rats. Therefore, novel MTK-loaded MS can be a promising liquid preparation, bettering oral absorption and patient's compliance.

In a sample of 442 births from the Child Health and Development Studies cohort, we examined associations between maternal prenatal exposure to hydroxylated polychlorinated biphenyl metabolites (OH-PCBs) and pregnancy outcomes, and whether associations were mediated by maternal thyroid hormone levels and/or modified by maternal smoking. Compared to nonsmokers, smokers had twice the mean concentration of 4-OH-CB107 (p

A novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA) in a crystalline state was structured to provide extended drug retention in joints after intra-articular (IA) injection. Microcrystals with a median diameter of 1.7 &mu, m were prepared by ultra-sonication method, and incorporated into poly(lactic-co-glycolic acid)/poly(lactic acid) (PLGA/PLA) MSs using spray-drying technique. Cross-sectional observation and X-ray diffraction analysis showed that drug microcrystals were evenly embedded in the MSs, with a distinctive crystalline nature of TA. In vitro drug release from the novel MSs was markedly decelerated compared to those from the marketed crystalline suspension (Triam inj.&reg, ), or even 7.2 &mu, m-sized TA crystals-loaded MSs. The novel system offered prolonged drug retention in rat joints, providing quantifiable TA remains over 28 days. Whereas, over 95% of IA TA was removed from joints within seven days, after injection of the marketed product. Systemic exposure of the steroidal compound was drastically decreased with the MSs, with &lt, 50% systemic exposure compared to that with the marketed product. The novel MS was physicochemically stable, with no changes in drug crystallinity and release profile over 12 months. Therefore, the TA microcrystals-loaded MS is expected to be beneficial in patients especially with osteoarthritis, with reduced IA dosing frequency.

The incorporation of permeation enhancers in topical preparations has been recognized as a simple and valuable approach to improve the penetration of antifungal agents into toenails. In this study, to improve the toenail delivery of efinaconazole (EFN), a triazole derivative for onychomycosis treatment, topical solutions containing different penetration enhancers were designed, and the permeation profiles were evaluated using bovine hoof models. In an in vitro permeation study in a Franz diffusion cell, hydroalcoholic solutions (HSs) containing lipophilic enhancers, particularly prepared with propylene glycol dicaprylocaprate (Labrafac PG), had 41% higher penetration than the HS base. Moreover, the combination of hydroxypropyl-β-cyclodextrin with Labrafac PG further facilitated the penetration of EFN across the hoof membrane. In addition, this novel topical solution prepared with both lipophilic and hydrophilic enhancers was physicochemically stable, with no drug degradation under ambient conditions (25 °C, for 10 months). Therefore, this HS system can be a promising tool for enhancing the toenail permeability and therapeutic efficacy of EFN.

Wild aquatic birds, a natural reservoir of avian influenza viruses (AIVs), transmit AIVs to poultry farms, causing huge economic losses. Therefore, the prevalence and genetic characteristics of AIVs isolated from wild birds in South Korea from October 2019 to March 2020 were investigated and analyzed. Fresh avian fecal samples (3256) were collected by active monitoring of 11 wild bird habitats. Twenty-eight AIVs were isolated. Seven HA and eight NA subtypes were identified. All AIV hosts were Anseriformes species. The HA cleavage site of 20 representative AIVs was encoded by non-multi-basic amino acid sequences. Phylogenetic analysis of the eight segment genes of the AIVs showed that most genes clustered within the Eurasian lineage. However, the HA gene of H10 viruses and NS gene of four viruses clustered within the American lineage, indicating intercontinental reassortment of AIVs. Representative viruses likely to infect mammals were selected and evaluated for pathogenicity in mice. JB21-58 (H5N3), JB42-93 (H9N2), and JB32-81 (H11N2) were isolated from the lungs, but JB31-69 (H11N9) was not isolated from the lungs until the end of the experiment at 14 dpi. None of infected mice showed clinical sign and histopathological change in the lung. In addition, viral antigens were not detected in lungs of all mice at 14 dpi. These data suggest that LPAIVs derived from wild birds are unlikely to be transmitted to mammals. However, because LPAIVs can reportedly infect mammals, including humans, continuous surveillance and monitoring of AIVs are necessary, despite their low pathogenicity.

A modular multichannel reaction module with microchannel-based coolant channels was considered, and a computational fluid dynamics (CFD) model was developed to describe the hydrodynamic behavior of the module. Reaction rates for the lumped chain length distribution of hydrocarbon products generated by the Fischer–Tropsch synthesis reaction were proposed, and the developed kinetic and CFD models were shown to satisfactorily fit the experimental data under different production rates. High heat transfer rates resulting from the use of microchannel-based cooling channel maintained the temperature peak below 10 °C, and simulation results with increased size of the catalytic bed and absence of inert materials showed that the high heat of reactions could be efficiently removed over entire catalytic beds, preventing the creation of local hot spots, which are usually observed in conventional fixed bed reactors. In addition, the efficient use of thermal energy could guarantee that methane selectivity, which needs t...

Carbon capture and storage (CCS) technologies are a cornerstone for reducing CO2 emissions from energy and energy-intensive industries. Among the various CCS technologies, solid sorbent looping systems are considered to be potentially promising solutions for reducing CO2 capture energy penalty. We present an evaluation module for a carbonator with sorbent looping cycle to calculate the carbonation efficiency. The module incorporates a simple sorbent activity model, and the solid/gas balances are constructed by assuming simple reactor mixing quality. By conducting simulations, we examine the variation in the carbonation efficiencies as a function of the sorbent looping operation factors and discuss an optimum operating strategy.

This paper presents a comparative study of wave height estimation method that was used for signal to noise ratio and shadowing ratio based on X-band marine radar. If the signal to noise ratio, and is widely used as a method for estimating an wave height, a new method is presented for shadowing ratio. In the case of radar images used in this study it is measuring the data from the coast of Ulsan Jujeon, compared with marine meteorological information from the Meteorological Agency measured a light beacon. We compared the measured data for about 34 days, the typhoon was measured, incluidng a period in the East Sea, and verify the results for various distribution of wave height. For estimate wave height using a shadowing ratio analysis, it does not require calibration and real-time advantages of this part, coming confirmed the possibility of the measurement, the cause detection error for radar image was caused due to determine.

Previously, we reported the potential of a novel Cdk inhibitor, 2-[1,1'-biphenyl]-4-yl-N-[5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-1H-indazol-3-yl]acetamide (BAI) as a cancer chemotherapeutic agent. In this study, we investigated mechanisms by which BAI modulates FTI-mediated apoptosis in human renal carcinoma Caki cells. BAI synergizes with FTI to activate DEVDase, cleavage of poly ADP-ribose polymerase (PARP), and degradation of various anti-apoptotic proteins in Caki cells. BAI plus LB42708-induced apoptosis was inhibited by pretreatment with pan-caspase inhibitor, z-VAD-fmk, but not by overexpression of CrmA. The ROS scavenger, N-acetylcysteine (NAC) did not reduce BAI plus LB4270-induced apoptosis. Co-treatment of BAI and LB42708 reduced the mitochondrial membrane potential (MMP, ∆Ψm) in a time-dependent manner, and induced release of AIF and cytochrome c from mitochondria in Caki cells. Furthermore, BAL plus LB42708 induced downregulation of anti-apoptotic proteins [c-FLIP (L), c-FLIP (s), Bcl-2, XIAP, and Mcl-1 (L)]. Especially, we found that BAI plus LB42708-induced apoptosis was significantly attenuated by overexpression of Bcl-2 and partially blocked by overexpression of c-FLIP (L). Taken together, our results show that the activity of BAI plus LB42708 modulate multiple components in apoptotic response of human renal Caki cells, and indicate a potential as combinational therapeutic agents for preventing cancer such as renal carcinoma.

This paper presents a sea surface reconstruction method that uses measured radar images by applying filtering techniques and identifying wave characteristics of the surrounding the Ieodo ocean research station using WaveFinder (X-band wave measurement radar), which is installed in the station. In addition, the results obtained from real radar images are used to verify the reconstructed sea surface. WaveFinder is a marine system that was developed to measure wave information in real time. The WaveFinder installed in the station could acquire sequent images for the sea surface at constant time intervals to obtain real time information (Wave height, mean wave period, wave directiona lity, etc.) for the wave by getting a three-dimensional spectrum by applying an FFT algorithm to the acquired sequent images and wave dispersion relation. In particular, we found the wave height using the SNR (Signal to noise ratio) of the acquired images. The wave information measured by WaveFinder could be verified by comparing and analyzing the results measured using the wave measurement instrument (Sea level monitor) in the station. Additionally, the wave field around the station could be reconstructed through the three-dimensional spectrum and the inverse FFT filtering from the analyzed results for the measured radar images. We verified the applicability of the sea surface reconstruction method by comparing the measured and simulated sea surfaces.

Production simulation technology is beneficial to solve the complicated and fluctuated problems in a shipyard. It takes too much time and effort to build simulation models in the field, though. This research proposes a feasible method to reduce the difficulties related to simulation modeling for the factory or shop capacity analysis. In addition, a proposed neutral data format for production information is efficient to manage information acquisition for simulation modeling automation. A panel block shop model is contributed to comparison between the conventional technique and the automated one. The automation technique is highly recommended to run a rapid simulation in the shipyard problem.

Introduction Numerous studies on cam femoroacetabular impingement (FAI) causing osteoarthritis have been conducted in Western populations, but not in Asian populations. The alpha angle in cam type FAI can be measured by routine hip AP and axial radiographs. The purpose of this study was to determine the range of alpha angles in an asymptomatic Asian cohort. Materials and Methods We performed a retrospective examination on 500 asymptomatic Asian adults (1000 hips) who underwent simultaneous spine MRI and hip coronal survey MRI for evaluation of back pain from December 2009 to March 2010. The alpha angle was measured on anteroposterior (AP) pelvic survey images. According to inclusion criteria, 372 hips of 186 men and 622 hips of 311 women were analysed. Results The mean alpha angles for men and women were 50.61° ± 7.61° and 49.82° ± 4.14°, respectively with no statistically significant differences (p = 0.063). Alpha angles of the two age groups (≥50 years old and Conclusions After review of 994 asymptomatic adult hips, we found neither gender-specific nor age-specific differences in the alpha angle. The frequency of the pathological range of the alpha angle was notably rare, as compared to those of Western countries. We assume that these findings could be related to a low prevalence of FAI and idiopathic osteoarthritis of the hip in the Asian population.

Small area LDO (Low drop-out) regulator with pass transistor using body-driven technique is presented in this paper. The body-driven technique can decrease threshold voltage (Vth) and increase the current ID flowing from drain to source in current. The technique is applied to the pass transistor to reduce size of area and maintain the same performance as conventional LDO regulator. A pass transistor using the technique can reduce its size by 5.5 %. The proposed LDO regulator works under the input voltage of 2.7 V ~ 4.5 V and provides up to 150mA load current for an output voltage range of 1.2 V ~ 3.3 V.

We demonstrate the effects of reduced cation ordering on the electrochemical properties of LiNi 0.5 Mn 1.5 O 4 . LiNi 0.5 Mn 1.5 O 4 is treated with nitric acid to reduce the degree of cation ordering. Nitric acid treatment induces partial oxidation of Ni 2+ to Ni 3+ as confirmed by X-ray photoelectron spectroscopy (XPS). Thanks to this oxidation, the 16d octahedral site in LiNi 0.5 Mn 1.5 O 4 is quite void of cation ordering and its structure is partially changed to more disordered spinel engaged in Fd3m . This structural change is accompanied by significantly enhanced electrochemical performances in rate capability as well as cyclic retention. Actually, nitric acid treated LiNi 0.5 Mn 1.5 O 4 can deliver about 87% of the initial capacity (129 mAh g −1 ) even after 100 cycles even at 55 °C.

In this paper, dc-dc buck converter controled by the peak current-mode pulse-width-modulation (PWM) presented. Based on the small-signal model, we propose the novel methods of the power stage and the systematic stability designs. To improve the reliability and performance, over-temperature and over-current protection circuits have been designed in the dc-dc converter systems. To prevent electrostatic An electrostatic discharge (ESD) protection circuit is proposed. The proposed dc-dc converter circuit exhibits low triggering voltage by using the gate-substrate biasing techniques. Throughout the circuit simulation, it confirms that the proposed ESD protection circuit has lower triggering voltage(4.1V) than that of conventional ggNMOS (8.2V). The circuit simulation is performed by Mathlab and HSPICE programs utilizing the 0.35um BCD (Bipolar-CMOS-DMOS) process parameters.

ObjectiveThe aim of this study was to assess the expression of DKK3 protein and its target, beta-catenin, in uterine cervical squamous cell carcinoma and to determine potential clinical correlations.Materials and MethodsSix carcinoma in-situ (CIS) tissues and 88 invasive cervical cancer tissues were included in the study. Twenty-two normal cervical tissues and one gastric cancer tissue were used as controls. The expression of DKK3 and beta-catenin proteins was evaluated by immunohistochemical analysis. Clinical and pathological parameters were obtained from medical records. Survival data were estimated using Kaplan-Meier estimates and compared with a log-rank test. Multivariate analysis was performed using the Cox regression method.ResultsDKK3 was predominantly present in the cytoplasm. Beta-catenin was observed only on the cellular membrane of both normal and cancer cells in contrast to earlier reports, in which beta-catenin was localized to the cytoplasm and nucleus of cancer cells. The expressions of beta-catenin and DKK3 were not correlated. Three of 6 CIS (50%) and 57 of 88 invasive cancer specimens (64.8%) had lower DKK3 expression than normal controls. DKK3 expression was decreased in a stage-dependent manner (P = 0.021). The patients with low expression of DKK3 were older than those with high expression of DKK3 (P < 0.01). Moreover, the patients with low DKK3 expression had a significantly lower 5-year disease-free survival rate than those with high DKK3 expression (P = 0.026). A multivariate analysis showed that International Federation of Gynecology and Obstetrics clinical stage and parametrial involvement were independent prognostic factors.ConclusionDecreased DKK3 expression was associated with advanced International Federation of Gynecology and Obstetrics clinical stages and was predictive of lower disease-free survival in patients with cervical squamous cell carcinoma. DKK3 may be implicated in cervical carcinogenesis through a beta-catenin–independent mechanism.

Brain aging is one of the most crucial biological processes that affect the physiological balance between health and disease. Age-associated dysfunction of brain leads to severe health problems in current aging society. MicroRNAs (miRNAs) have emerged as important regulators in most physiological processes including fine-tuning of the short-term, cellular regulatory functions as well as modulation of long-term organismal lifespan. In this review, we discuss critical roles of miRNAs in the progression of normal and pathological brain aging. 50% of all known miRNAs are found in brain including cortex and hippocampus. A significant number of expressed miRNAs were differentially regulated during aging, implicating miRNAs as regulators of brain aging. The ability of miRNAs to regulate multiple targets within a pathway or even multiple pathways allows for coordinated regulation of brain functions. miRNA-mediated, brain functional changes are evident in cognition, inflammation, neuroprotection, lipid metabolism, mitochondrial function and lifespan. Dysregulation of brain miRNAs contributes to accelerated cognitive decline and increased neurological disorders. Elucidating mechanisms by which miRNAs and their multiple targets are temporally and spatially regulated in normal and pathological brain aging will provide a deeper understanding on the process of interrelated pathways of brain aging, and a new insight into therapeutic interventions.

The proposed method for ocean surface wave is carried out by a statistical analysis of the x-band marine radar image. In particular, by using the Fast Fourier Transform in 3-dimensional method and the linear dispersion relation derives a parameter of the ocean wave such as significant wave height and peak wave period. For the ocean surface wind measurements using radar cross section, and the image superposition method is used. Signal to Noise Ratio is used to measure wave height and wind velocity. Wave height, wave period, wind velocity, and wind direction were used for a long period of time, measuring the data from the IEODO ocean research station in Republic of Korea to the validation. In addition, compared with the measurement results of the light beacon in the radar image boundary and radar system located on the coast. The results were in good agreement with the quantitative analysis, the possibility of commercialization could be founded. Comparison data were obtained through the cooperation of the Republic of Korea Meteorological Administration and the National Oceanographic Research Institute. It is possible to use the measurement of wind and wave radar mounted on ships and offshore plants. This system benefits the efficiency of the plant operation.

점진성형(Incremental forming)의 시초는 농기구 등을 생산하기 위해서 해머를 이용하여 소재를 조금씩 두들겨서 소재의 형상을 구현한 공정이라고 Key Words: Incremental Forming(점진성형), Description Scheme(묘사 기법), Finite Element Analysis(유한요소해석), Lagrangian Description(라그랑지언 묘사), ALE Description(에이엘이 묘사) 초록: 점진성형은 공구 운동으로 소재의 국부 소성변형 영역을 전체 소재에 확장시켜 목표 형상으로 변형시키는 냉간 성형공정이다. 본 논문에서는 점진성형의 유한요소해석 시 묘사기법에 관한 연구를 수행하였다. 고찰할 묘사기법으로 라그랑지언 묘사법과 ALE 묘사법을 선택하였다. 미끄럼 경계기법도 공구와 접촉표면에서 요소의 찌그러짐을 극복하기 위한 방법중의 한가지 경우로 고찰하였다. 묘사기법과 경계기법의 다양한 조합 중에 ALE 묘사법과 연계한 미끄럼 경계기법의 경우가 요소의 찌그러짐을 가장 완화 시켰다. 이 방법이 최종 단계 변형까지 점진성형 해석을 지속할 수 있도록 해주는 유일한 조합인 것으로 나타났다. 이에 반해, 라그랑지언 묘사법 및 순수 ALE 묘사법은 점진성형 해석 중에 요소의 찌그러짐이 극심하여 최종 변형 형상에 도달하기 오래 전에 해석이 중단되는 상태를 보였다. Abstract: Incremental forming is a cold working process in which a small part of the material is being deformed and the area of local deformation is moving over the entire material. In this paper, we study description schemes to perform finite element analysis for the incremental forming. The selected description schemes to examine are the Lagrangian description and the arbitrary Lagrangian-Eulerian (ALE) description. The sliding boundary scheme coupled with ALE is also examined to overcome the distortion problems of elements on the contact surface. Results show that the ALE description with the sliding boundary scheme is most favorable in overcoming the distortion of elements. This description leads to make the simulation continued to the final stage of the incremental forming. On the other hand, the Lagrangian description as well as the original ALE description makes the elements much distorted and the analysis is stopped long before arriving at the final shape of deformation.

Obesity has recently been defined as a chronic inflammatory disease and is considered as a major cause of adult health problems including incurable diseases like diabetes and cancer. In this study, the systemic immunity, including the innate and adaptive immunity parameters, of naturally occurring (leptin receptor mutation) obesity-diabetes mice (db/db) was examined to increase our knowledge of these mice for obesity-related studies. Severe fatty liver with blood engorgement was observed in the db/db mice. Compared to background C57BL/6J mice, the adaptive immunity, as measured by mitogen-induced T and B cell proliferation and cytokine release, was significantly suppressed in db/db mice. However, significant upregulation of innate immune-inflammatory parameters including macrophage function and NK cell activity was observed in db/db mice without external stimulation. These data conclusively confirm the systemic immune-inflammatory micro-environment with suppressed adaptive immunity of db/db mice, which may cause the secondary obesity-related life-threatening diseases like diabetes or cancer.

In this study, we demonstrate for the first time that cystamine, an inhibitor of transglutaminase 2 (TG2), enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in Caki cells, but not in normal human mesangial cells. Cystamine plus TRAIL-induced down-regulation of c-FLIP was recovered to basal levels by addition of the pancaspase inhibitor, z-VAD. The forced expression of c-FLIP attenuated cystamine plus TRAIL-mediated apoptosis in Caki cells. Although, cells expressing high levels of TG2 were more sensitive to cystamine plus TRAIL-mediated apoptosis than were cells expressing low levels of TG2, cystamine plus TRAIL-mediated apoptosis in the cell line expressing high levels of TG2 was reduced when TG2 levels were knocked down with siRNA. These results indicate that the level of TG2 modulates cystamine plus TRAIL-induced apoptosis. Taken together, the present findings suggest that cystamine may be an effective sensitizer of TRAIL-induced apoptosis in cancer cells expressing high levels of TG2.

Replication Protein A (RPA) is a single stranded DNA-binding protein involved in DNA metabolic activities such as replication, repair, and recombination. RPA-Interacting Protein alpha (RIPalpha) was originally identified as a nuclear transporter of RPA in Xenopus. The human RIPalpha gene encodes several splice isoforms, of which hRIPalpha and hRIPbeta are the major translation products in vivo. However, limited information is available about the alternative splicing of RIPalpha in eukaryotes, apart from that in humans. In this study, we examined the alternative splicing of RIPalpha in the Drosophila, Xenopus, and mouse system. We showed that the number of splice isoforms of RIPalpha was species-specific, and displayed a tendency to increase in higher eukaryotes. Moreover, a mouse ortholog of hRIPbeta, mRIPbeta2, was not SUMOylated, in contrast to hRIPbeta. Based on these results, we suggest that the RIPalpha gene gains more splice isoforms and additional modifications after molecular evolution. [BMB reports 2009; 42(1): 22-27].

The inhibition of topoisomerase can suppress the growth of cancer cells and induce apoptosis. The aim of this study was to evaluate the anticancer effects and mechanisms of action of a novel topoisomerase inhibitor, 4-(furan-2-yl)-2-(pyridin-2-yl)-5,6-dihydro-1,10-phenanthroline (FPDHP). FPDHP suppressed the growth of Caki, A549, HT29 and MDA-MB-231 cells, and induced caspase-dependent apoptosis in the Caki cells. In particular, FPDHP also induced caspase-dependent apoptosis and the downregulation of the protein expression levels of cellular FLICE-like inhibitory protein (cFLIP) and the phosphorylation of Akt in Caki cells. Notably, the overexpression of cFLIP, but not that of Akt, in part, blocked the FPDHP-mediated apoptosis in Caki cells. In addition, FPDHP was further shown to induce the caspase-independent detachment of Caki cells from the culture dish; higher populations of apoptotic cells were observed in the detached cells than in the attached cells. To the best of our knoweledge, these results collectively demonstrate for the first time that FPDHP has a killing effect on Caki cells, which is mediated through both caspase-dependent apoptosis and caspase-independent cell detachment.

In this study, changes in fluid impact loads inside a tank were examined according to a two-row tank arrangement in an LNG-FPSO (Liquefied Natural Gas-Floating Production Storage Offloading) vessel. The motion RAO (Response Amplitude Operator) of the LNG-FPSO, coupled with the sloshing phenomenon inside the tank, was calculated by using HydroStar by Bureau Veritas. The motion simulation in the tank was conducted under filling ratios of 30%H, 60%H, and 80%H. The RAO in each condition was calculated according to the one-row and the two-row tank arrangement. The motion response spectrum using the calculated RAO and the JONSWAP (Joint North Sea Wave Analysis Project) spectrum were computed by implementing irregular motion according to each filling ratio and tank arrangement. The sloshing phenomenon inside the tank was implemented by using a 6-DOF (Degree Of Freedom) sloshing motion platform; impact pressure on the walls of the tank was measured with pressure sensors installed inside the tank. The sloshing experiment was conducted under the three filling ratios in the one-row and the two-row tank arrangement and impact loads were compared under each filling ratio according to the one-row and the two-row tank arrangement.

This paper presents the results of a study investigating methods of wave directionality based on wavelet transform. In part 1 of this paper, the theoretical background and characteristics of directional wavelet were discussed. Morlet wavelet and Cauchy wavelet were examined to test their efficiency in detection of directionality in signals. These wavelets were tested on numerical images which were considered to describe the basic characteristics of directionality of ocean waves.

This paper presents the results of a study investigating methods of interpretation of wave directionality based on wavelet transform. In part 1 of this paper, the tools to be used in detection of wave directionality, i. e., the Morlet and Cauchy wavelets, were described. This paper presents the application results of the directional wavelet to numerically generated images and video images taken in laboratory wave flume, river, and sea. The results showed that directional wavelet transform can be an efficient tool in detecting wave directionality with extremely low effort and cost when it is compared to traditional practices in use.

Small size and high performance LDO regulator using body driven technique is presented in this paper. The body driven technique can decrease threshold voltage (Vth) and increase the current I D flowing from drain to source in current. The technique is applied to the error amplifier, voltage buffer and pass transistor to reduce chip size and maintain the same performance as conventional LDO regulator. The pass transistor using the technique can reduce the size 5.4% compared with conventional pass transistor at 150mA load condition. The proposed current mirror in error amplifier and voltage buffer can save the area about 61% compared with the conventional current mirror. The proposed LDO regulator works under the input voltage of 2.7V∼4.5V and provides up to 150mA load current for an output voltage range of 1.2∼3.3V.