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The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.

Study Objective Despite the benefits of patient-centered contraceptive care, many adolescents and young adults do not receive such care. The objective of this study was to develop and evaluate Hello Options, a tangible decision aid to support patient-centered contraceptive counseling with adolescents and young adults in a clinic setting. Design, Setting, Participants, Intervention, and Main Outcome Measures Hello Options is a contraceptive counseling decision aid tool (hereafter referred to as "the Tool") that allows patients to see and feel life-size “tangible” models of the range of contraceptive methods. The Tool was developed by a team of designers, adolescents, clinicians, and researchers using human-centered design. From December 2019 to March 2020, we conducted a pilot study to evaluate the usability, feasibility, and acceptability of the Tool with 10 contraceptive care providers and 40 adolescent and young adult patients (aged 12-29 years) at two Chicago clinics. We calculated descriptive statistics for patient survey data, and qualitatively analyzed provider interview transcripts for salient themes using recursive abstraction. Results Patients had positive reactions to the Tool, reporting that it allowed them to better understand how contraceptive methods work in their body and that it allowed them to make more informed decisions. Furthermore, providers commented that the Tool facilitated conversations with their patients, helped dispel myths about particular methods, and eased patients’ anxieties. Limitations mentioned included storage and portability concerns, and time constraints for counseling. Conclusion Hello Options is a useful, feasible, and acceptable decision aid that can support the provision of patient-centered contraceptive care for young people.

Various methods of combining facial and intraoral information have been described. However, overlapping errors lead to errors. This article describes a 3D face model that uses a UV mapping technique. The combination of soft-tissue information extracted from cone beam computed tomography (CBCT) and a straightforward facial photograph provides more accurate data than with conventional methods.

Detecting machine mode can allow smarter process monitoring systems and more accurate fault prediction without external information. A remote machine monitoring system was installed on a cold heading machine in the factory of an automotive fastener manufacturing company. The process monitoring system was non-intrusive and was designed to measure vibration. The end goal of the study was to predict tool wear, but part classification was required first, as the machine produced multiple parts which produced different vibration signals. The collected vibration data was processed using wavelet transform and passed through a convolutional neural network for part classification. This method achieved part classification accuracy as high as 86% when looking at data for a 1-month period. The results show that meaningful classification features are present in the data using the process monitoring system as designed.

Osteoclast-associated receptor (OSCAR) is a member of the leukocyte receptor complex (LRC)-encoded protein family, which is characterized by the presence of immunoglobulin (Ig)-like domains. OSCAR recognizes collagen and was first identified as a co-stimulatory receptor that is needed for complete osteoclast differentiation. However, it is now clear that OSCAR is also expressed by multiple immune cells that participate in many innate and adaptive immune cell activities. We also showed recently that chondrocytes express OSCAR. Our and other studies suggest that OSCAR participates in the pathogenesis of two common joint diseases, namely, rheumatoid arthritis (RA) and osteoarthritis (OA). Specifically, OSCAR promotes osteoclast formation and therefore bone erosion in RA while in OA, it triggers chondrocyte death, thereby inducing cartilage fragility. Significantly, blocking the interaction of OSCAR with its collagen ligand can markedly reduce these activities in vitro and in vivo. Thus, this novel approach may have therapeutic potential for joint diseases.

Duplication of complete dentures by using digital technology is now widely practiced. However, the method of accepting only the cameo surface of dentures and forming a new artificial tooth arrangement by using analog techniques is still complex and time-consuming. A method for creating a new denture by implementing various artificial tooth arrangements by using a computer-aided design (CAD) software program after importing the existing denture cameo surface as is into the software is introduced. The technique helps solve patient discomfort due to occlusal problems in patients with complete dentures.

Group A rotaviruses (RVAs) are important gastroenteric pathogens that infect humans and animals. This study aimed to analyze the complete genome sequence, i.e., 11 genome segments of the lapine rotavirus (LRV) identified in the intestine of a dead rabbit in the Republic of Korea (ROK) and to describe the genetic relationships between this lapine isolate [RVA/Rabbit-wt/KOR/Rab1404/2014/G3P[22] (Rab1404)] and other lapine isolates/strains. Rab1404 possessed the following genotype constellation: G3-P[22]-I2-R3-C3-M3-A9-N2-T3-E3-H3. The P[22] genotype was found to originate from rabbits and was for the first time identified in the ROK. Phylogenetic analysis showed that Rab1404 possessed VP1-3 and VP7 genes, which were closely related to those of the bat strain LZHP2; NSP1-4 genes, which were closely related to those of the simian strain RRV; and VP4, VP6, and NSP5 genes, which were closely related to the genes obtained from other rabbits. Interestingly, a close relationship between Rab1404 and simian RVA strain RVA/Simian-tc/USA/RRV/1975/G3P[3] for 8 gene segments was observed. RRV is believed to be a reassortant between bovine-like RVA strain and canine/feline RVA strains. Rab1404 and canine/feline RVAs shared the genes encoding VP1, VP3, VP7, NSP3, and NSP4. Additionally, the genome segments VP6 (I2), NSP1 (N2), and NSP5 (H3) of Rab1404 were closely related to those of bovine RVAs. This is the first report describing the complete genome sequence of an LRV detected in the ROK. These results indicate that Rab1404 could be a result of interspecies transmission, possibly through multiple reassortment events in the strains of various animal species and the subsequent transmission of the virus to a rabbit. Additional studies are required to determine the evolutionary source and to identify possible reservoirs of RVAs in nature., Highlights • This is the first report to describe the complete genome sequence of a rabbit rotavirus (Rab1404) detected in the ROK. • The 11 genome segments of Rab1404 were determined; G3-P[22]-I2-R3-C3-M3-A9-N2-T3-E3-H3. • G3P[22] identified in this study is found to originate from rabbit and may have more species specificity. • Rab1404 could be a result of multiple reassortment events from strains originating from various animal species and transmitted to the rabbit.

Deep learning-based methods are attracting interest in sound source localization, showing promising results compared to conventional model-based approaches. While these deep learning-based methods have been mainly developed into two approaches, i.e., grid-based and grid-free methods, they inherently involve several limitations that the sound sources should be assumed on the grid points or the number of sound sources should be pre-defined when constructing a deep neural network’s architecture. Breaking away from the existing methods’ limitations, we propose a deep learning approach to fulfill multiple sound source localization with high resolution and accuracy, for whether the sound sources are located on the grid points or not. We first suggest a target function to obtain spatial source distribution maps, that can represent multiple sources’ positional and strength information, even when the sources are placed off the grid points. While the multiple sound source localization is expanded by the proposed source map into image-to-image pixel-level prediction task, we then propose a fully convolutional neural network (FCN) with an encoder-decoder structure to estimate the multiple sources’ positions and strength precisely. Based on the dataset acquired by one to three monopole sources on a square plane of 2.68 × 2.68 m, with a spiral array of 60 microphones at 1, 2, and 10 kHz, we assess both quantitative and qualitative results of the proposed model and demonstrate that our proposed model can achieve highly precise localization results regardless of frequency and the number of sound sources. Besides, we validate that high-resolution source distribution maps can be obtained by the proposed model, from which the positions and the strengths of sound sources are accurately predicted. Lastly, we compare the proposed model with several deconvolution methods, and the results show that the proposed deep learning model significantly outperforms the model-based methods.

Excessive bone resorption caused by increased osteoclast number or activity leads to a variety of bone diseases including osteoporosis, rheumatoid arthritis and periodontitis. Thus, the therapeutic strategy for these diseases has been focused primarily on the inhibition of osteoclast formation and function. This study shows that euphorbia factor L1 (EFL1), a diterpenoid isolated from Euphorbia lathyris, inhibited osteoclastogenesis and induced osteoclast apoptosis. EFL1 suppressed osteoclast formation and bone resorption at both initial and terminal differentiation stages. EFL1 inhibited receptor activator of NF-κB ligand (RANKL)-induced NFATc1 induction with attenuated NF-κB activation and c-Fos expression. EFL1 decreased the level of reactive oxygen species by scavenging them or activating Nrf2, and inhibited PGC-1β that regulates mitochondria biogenesis. In addition, EFL1 induced apoptosis in differentiated osteoclasts by increasing Fas ligand expression followed by caspase activation. Moreover, EFL1 inhibited inflammation-induced bone erosion and ovariectomy-induced bone loss in mice. These findings suggest that EFL1 inhibits osteoclast differentiation by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast, and may provide therapeutic potential for preventing or treating bone-related diseases caused by excessive osteoclast.

A sensitive and selective capillary electrophoresis-mass spectrometry (CE-MS) method for determination of saturated fatty acids (FAs) was developed by using dicationic ion-pairing reagents forming singly charged complexes with anionic FAs. For negative ESI detection, 21 anionic FAs at pH 10 were separated using ammonium formate buffer containing 40% acetonitrile modifier in normal polarity mode in CE by optimizing various parameters. This method showed good separation efficiency, but the sensitivity of the method to short-chain fatty acids was quite low, causing acetic and propionic acids to be undetectable even at 100 mgL −1 in negative ESI-MS detection. Out of the four dicationic ion-pairing reagents tested, N,N’ -dibutyl 1,1’-pentylenedipyrrolidium infused through a sheath-liquid ion source during CE separation was the best reagent regarding improved sensitivity and favorably complexed with anionic FAs for detection in positive ion ESI-MS. The monovalent complex showed improved ionization efficiency, providing the limits of detection (LODs) for 15 FAs ranging from 0.13 to 2.88 μg/mL and good linearity ( R 2 > 0.99) up to 150 μg/mL. Compared to the negative detection results, the effect was remarkable for the detection of short- and medium-chain fatty acids. The optimized CE-paired ion electrospray (PIESI)-MS method was utilized for the determination of FAs in cheese and coffee with simple pretreatment. This method may be extended for sensitive analysis of unsaturated fatty acids.

Identifying phase information of high-entropy alloys (HEAs) can be helpful as it provides useful information such as anticipated mechanical properties. Recently, machine learning methods are attracting interest to predict phases of HEAs, which could reduce the effort for designing new HEAs. As research direction is in its infancy, there is still plenty of room to develop machine learning models to improve the prediction accuracy and further guide the design of HEAs. In this work, we employ deep learning-based methods regarding optimization, generation, and explanation, for enhancing the performance and identifying key design parameters for phase prediction of HEAs. We first establish regularized deep neural networks for predicting HEA phases and optimize hyper-parameters concerning model architecture, training, and regularization. To overcome data shortage of HEAs, we then focus on developing conditional generative adversarial network for generating additional HEA samples. We observe the augmentation from our generative model significantly improves model performance, achieving prediction accuracy of 93.17%. Lastly, we concentrate on understanding contributions of design parameters to identifying solid solution (SS) phase as an example. Our work delivers guidance not only for developing a reliable deep learning-based phase prediction model, but for explaining significant design parameters to assist design of novel HEAs.

Coleoptera is a group of insects that are most diverse among insect resources. Although used as indicator species and applied in developing new drugs, it is difficult to identify them quickly. Since the development of a method using mitochondrial DNA information for identification, studies have been conducted in Korea to swiftly and accurately identify species. The National Science Museum of Korea (NSMK) has been collecting and morphologically identifying domestic reference insects since 2013, and building a database of DNA barcodes with digital images. The NSMK completed construction of a database of digital images and DNA barcodes of 60 beetle species in the Korean National Research Information System. A total of 179 specimens and 60 species were used for the analysis, and the averages of intraspecific and interspecific variations were 0.70±0.45% and 26.34±6.01%, respectively, with variation rates ranging from 0% to 1.45% and 9.83% to 56.23%, respectively.

A human hybrid cell line, F2N78, was developed by somatic fusion of HEK293 and Namalwa cells for the production recombinant biopharmaceutical proteins. In this study, we performed perfusion culture to verify its potential in culture process used for human cell expression platform. Cell viability could be maintained over 90% and high viable cell density was obtained at higher than 1.0 × 10(7) cells/mL by bleeding process in perfusion culture. The cells were adapted well in both culture modes, but there were apparent differences in protein quality. Compared to fed-batch culture, degalactosylated forms such as G0F and G0 as well as Man5 showed no significant increases in perfusion culture. In terms of charge variants, acidic peaks increased, whereas main peaks constantly decreased according to the length of culture period in both methods.

As the first example of the facile and rapid one-step synthesis of block copolymers, a range of poly (2-oxazoline) (POx)-based block copolymers were synthesized in a one-step procedure under microwave irradiation in a significantly shortened period of time using 4-cyano-4-(dodecylthiocarbonothioylthio)pentyl-4-methylbenzenesulfonate (CDPS) as a dual initiator for living cationic ring-opening polymerization (CROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization. 2-Methyl- and 2-ethyl-2-oxazoline were polymerized for the POx block via CROP, and methyl acrylate, methyl methacrylate, N , N -dimethylacrylamide, N , N -diethylacrylamide, N -isopropylacrylamide, and 4-acryloylmorpholine were polymerized for the other block via RAFT polymerization. The CROP and RAFT polymerization proceeded independently in a controlled manner.

Parkin is an E3 ligase that contains a ubiquitin-like (UBL) domain in the N terminus and an R1-in-between-ring-RING2 motif in the C terminus. We showed that the UBL domain specifically interacts with the R1 domain and negatively regulates Parkin E3 ligase activity, Parkin-dependent mitophagy, and Parkin translocation to the mitochondria. The binding between the UBL domain and the R1 domain was suppressed by carbonyl cyanide m-chlorophenyl hydrazone treatment or by expression of PTEN-induced putative kinase 1 (PINK1), an upstream kinase that phosphorylates Parkin at the Ser-65 residue of the UBL domain. Moreover, we demonstrated that phosphorylation of the UBL domain at Ser-65 prevents its binding to the R1 domain and promotes Parkin activities. We further showed that mitochondrial translocation of Parkin, which depends on phosphorylation at Ser-65, and interaction between the R1 domain and a mitochondrial outer membrane protein, VDAC1, are suppressed by binding of the UBL domain to the R1 domain. Interestingly, Parkin with missense mutations associated with Parkinson disease (PD) in the UBL domain, such as K27N, R33Q, and A46P, did not translocate to the mitochondria and induce E3 ligase activity by m-chlorophenyl hydrazone treatment, which correlated with the interaction between the R1 domain and the UBL domain with those PD mutations. These findings provide a molecular mechanism of how Parkin recruitment to the mitochondria and Parkin activation as an E3 ubiquitin ligase are regulated by PINK1 and explain the previously unknown mechanism of how Parkin mutations in the UBL domain cause PD pathogenesis.

Background: Although the prevalence of anaphylaxis is increasing worldwide, the large-scale studies in Asia evaluating anaphylaxis in all age groups are limited. We aimed to collect more precise and standardized data on anaphylaxis in Korea using the first multicenter web-based registry. Methods: Twenty-two departments from 16 hospitals participated from November 2016 to December 2018. A web-based case report form, designed by allergy specialists, was used to collect anaphylaxis data. Results: Within the 2-year period, 558 anaphylaxis cases were registered. The age of registered patients ranged from 2 months to 84 years, and 60% were aged

Mitochondrial dysfunction is implicated in the pathophysiology of major depressive disorder (MDD). This dysfunction can be indirectly assessed using the mitochondrial DNA (mtDNA) copy number. A total of 118 patients with MDD and 116 age- and sex-matched control subjects were recruited for this study, and mtDNA copy numbers were measured in peripheral blood cells. This study also examined the potential variables that might impact mtDNA copy number in MDD, including age and clinical features. Additionally, epigenetic control of mtDNA copy number was examined by assessing DNA methylation ratios in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) promoter in nuclear DNA and the displacement loop (D-loop) region of mtDNA. The present results showed that patients with MDD had a higher mtDNA copy number and a decreased DNA methylation status in the PGC1α promoter. mtDNA copy numbers were negatively associated with an age, psychomotor agitation, and somatic symptoms in MDD. These results suggest that the alterations in mitochondrial function and epigenetic change of PGC1α may be relevant to the pathophysiology of MDD.

In this paper, we propose multi-layer non-negative matrix factorization (NMF) network for classification task, which provides intuitively understandable hierarchical feature learning process. The layer-by-layer learning strategy was adopted through stacked NMF layers, which enforced non-negativity of both features and their coefficients. With the non-negativity constraint, the learning process revealed latent feature hierarchies in the complex data in intuitively understandable manner. The multi-layer NMF networks was investigated for classification task by studying various network architectures and nonlinear functions. The proposed multilayer NMF network was applied to document classification task, and demonstrated that our proposed multi-layer NMF network resulted in much better classification performance compared to single-layered network, even with the small number of features. Also, through intuitive learning process, the underlying structure of feature hierarchies was revealed for the complex document data.

Activation of NK cells is triggered by combined signals from multiple activating receptors that belong to different families. Several NK cell activating receptors have been identified, but their role in the regulation of effector functions is primarily understood in the context of their individual engagement. Therefore, little is known about the signaling pathways broadly implicated by the multiple NK cell activation cues. Here we provide evidence pointing to glycogen synthase kinase (GSK)-3β as a negative regulator of multiple NK cell activating signals. Using an activation model that combines NKG2D and 2B4 and tests different signaling molecules, we found that GSK-3 undergoes inhibitory phosphorylation at regulatory serine residues by the engagement of NKG2D and 2B4, either individually or in combination. The extent of such phosphorylation was closely correlated with the degree of NK cell activation. NK cell functions, such as cytokine production and cytotoxicity, were consistently enhanced by the knockdown of GSK-3β or its inhibition with different pharmacological inhibitors, whereas inhibition of the GSK-3α isoform had no effect. In addition, NK cell function was augmented by the overexpression of a catalytically inactive form of GSK-3β. Importantly, the regulation of NK cell function by GSK-3β was common to diverse activating receptors that signal through both ITAM and non-ITAM pathways. Thus, our results suggest that GSK-3β negatively regulates NK cell activation and that modulation of GSK-3β function could be used to enhance NK cell activation.

Display Omitted Behaviors of LER caused by the stochastic exposure have been analyzed.LER decreases from the inside of a feature to the outside.LER is smaller for a higher beam energy, a higher dose, or a thinner resist.LER is smaller for a smaller exposing interval, or an upper layer of the resist.Shot noise has less effect on LER for a higher dose or an upper layer of resist. The line edge roughness (LER) has become one of the critical issues which affect the minimum feature size and the maximum circuit density realizable in most lithographic processes. Since the LER does not scale with the feature size, it needs to be minimized as the feature size is reduced well below 100nm. One of the main factors contributing to the LER is the stochastic fluctuation of exposure. In the past, most of the LER researches were based on a 2-D model without considering the resist depth dimension. In this study, the dependency of the LER, caused by the stochastic fluctuation of exposure due to electron scattering in the resist and the shot noise due to variation of electron influx, on lithographic parameters such as shot noise, beam energy, exposing interval, dose, etc., has been investigated with a 3-D model, as the first step toward developing an effective method for minimizing the LER. In the case of CAR, the effect of developing process on LER is also considered. In this paper, the results from an extensive simulation are reported with a detailed discussion.

Diseases caused by many Gram-negative bacterial pathogens depend on the activities of bacterial effector proteins that are delivered into eukaryotic cells via specialized secretion systems. Effector protein function largely depends on specific subcellular targeting and specific interactions with cellular ligands. PDZ domains are common domains that serve to provide specificity in protein-protein interactions in eukaryotic systems. We show that putative PDZ-binding motifs are significantly enriched among effector proteins delivered into mammalian cells by certain bacterial pathogens. We use PDZ domain microarrays to identify candidate interaction partners of the Shigella flexneri effector proteins OspE1 and OspE2, which contain putative PDZ-binding motifs. We demonstrate in vitro and in cells that OspE proteins interact with PDLIM7, a member of the PDLIM family of proteins, which contain a PDZ domain and one or more LIM domains, protein interaction domains that participate in a wide variety of functions, including activation of isoforms of protein kinase C (PKC). We demonstrate that activation of PKC during S. flexneri infection is attenuated in the absence of PDLIM7 or OspE proteins and that the OspE PDZ-binding motif is required for wild-type levels of PKC activation. These results are consistent with a model in which binding of OspE to PDLIM7 during infection regulates the activity of PKC isoforms that bind to the PDLIM7 LIM domain.

A three-dimensional (3-D) remaining resist profile often needs to be estimated and examined especially for nanoscale feature. However, conventional methods, such as the cell removal method and fast marching method, require intensive computation, and therefore are too time-consuming to be employed for large patterns such as a mask or an iterative procedure such as proximity effect correction (PEC). In this paper, a new method for 3-D resist development simulation has been developed for fast and accurate simulation of simple patterns such as lines and rectangles. It employs the concept of “development paths” to model the development process. In order to reduce the simulation time, each path is examined individually without a time-consuming iterative procedure which is adopted by conventional methods. An adaptive scheme has also been incorporated into the proposed simulation method, which further reduces the simulation time without sacrificing simulation accuracy substantially. The simulation results show that the proposed method achieves resist profiles well matched with those by conventional methods, even for more general patterns, but reducing simulation time by orders of magnitude, and the speed-up is larger for a larger pattern. Also, the accuracy of the proposed method has been verified experimentally.

Thermostable disproportionation enzymes active at around the gelatinization temperature of rice starch (70–80 °C) were used to improve the quality of cooked rice with lump-free properties. Cyclodextrin glucanotransferase from Pyrococcus furiosus (CGTase) and a starch binding domain-attached alpha-glucanotransferase from Thermus aquaticus (αGTase) were prepared from an Escherichia coli transformant carrying a recombinant plasmid. The stickiness determined by a texture analyzer showed that both enzymes had the effect of reducing the lumping properties of cooked rice grains and rice porridge. The enzyme treatment also provided a finer, creamier, and more uniform texture of rice porridge. An HPAEC analysis of the starch structure in cooked rice and rice porridge revealed that the proportion of both short (DP 20) increased in the enzyme-treated samples. Additionally, the amylose content of the cooked rice grain treated with αGTase and CGTase decreased by 36% and 30%, whereas that of porridge was reduced by 36% and 35%, respectively. In particular, the amylose content on the surface of the enzyme-treated cooked rice grains was reduced by 50% compared with that of untreated cooked rice. These results indicated that the glucan segment of amylose was transferred to amylopectin branch chains by a transferring reaction with both enzymes, reducing the amylose content of grains during cooking. Mechanistically, the decrease in the amylose content filmed on the surface is likely to be responsible for reducing the stickiness of cooked rice grains and rice porridge. Furthermore, the retrogradation rate determined by a differential scanning calorimeter was significantly reduced in the enzyme-treated samples after storage for 10 h at 4 °C. The decrease in long-chain amyloses, may lead to the retardation of re-crystallization. These physicochemical properties of the modified cooked rice and rice porridge can be applied to various rice-based products in the food industry.

The increasing incidence of food allergy (FA) can be attributed to interactions between genes and the environment, but these interactions are not yet fully clear.We aimed to evaluate the interaction between infant genetic variations and maternal dietary patterns to identify risk factors in the development of FA.We used the Cohort for Childhood Origin of Asthma and allergic diseases birth cohort of 1628 infants, born between 2007 and 2015. Maternal dietary intakes were assessed at 26 weeks of pregnancy using a food frequency questionnaire and grouped according to 5 dietary patterns. Infant cord blood samples were genotyped at 12 loci.Among 1628 infants, 147 (9.0%) were diagnosed with FA based on history. A maternal confectionery diet characterized by a higher intake of baked and sugary products during pregnancy was associated with a higher prevalence of FA (adjusted odds ratio [OR] = 1.517, P = .02); this dietary pattern tended to be higher in trans fat (r = 0.498, P.001). Development of FA was associated with longer periods of breastfeeding (adjusted OR = 1.792, P = .03), and this dietary pattern was more significantly related to the development of FA in infants with the homozygous TT genotype of CD14 (rs2569190) and more than 1 copy of GSTM1 and GSTT1.A maternal confectionery diet during pregnancy that majorly consists of baked and sugary products, combined with a longer ensuing period of breastfeeding, may lead to the development of FA, suggesting a harmful effect of trans fats in the infant. Polymorphisms in CD14 and GST in the infant influence FA susceptibility.

Although Toll-like receptors (TLRs) have been implicated in the regulation of stem cell functions, their role in osteogenic differentiation of adipose-derived stromal cells (ASCs) has not been reported. We found that ASCs express a restricted subset of TLRs, including TLR1–TLR5, and that TLR agonists such as Pam3CSK4 (TLR1/2 agonist), polyinosinic:polycytidylic acid (TLR3 agonist), lipopolysaccharide (TLR4 agonist), and flagellin (TLR5 agonist), but not R848 (TLR7/8 agonist), consistently induced osteogenic differentiation in murine-derived ASCs, which coincided with the TLR expression pattern of ASCs. Cytokine expression profiles induced by TLR agonists and results from subsequent functional assays indicated that interleukin-6 (IL-6) together with soluble IL-6 receptor (sIL-6R) enhanced osteogenic differentiation of ASCs by activating STAT3. Small interfering RNA (siRNA)-mediated STAT3-silencing blunted osteogenesis and the expression of osteogenic markers, whereas STAT3 overexpression resulted in an increase in osteogenesis. Consistently, STAT3 inhibitor treatment reduced osteogenesis, STAT3 phosphorylation, and expression of osteogenic markers including osterix. Chromatin immunoprecipitation (ChIP) assays indicated that STAT3 binding to the STAT3-binding sites on the osterix promoter increased during IL-6-stimulated osteogenesis. Our results thus establish TLRs as novel regulators of ASCs which signal through IL-6/STAT3 pathway and induce osterix expression as a part of the osteogenesis.

Microalgae are a potential resource for biodiesel production. A green alga, Chlorella sp., was isolated from Arctic sea ice, which was named ArM0029B. These algae displayed faster growth at a wide temperature range of 4-32°C compared to Chlorella vulgaris. ArM0029B also accumulated high levels of total fatty acids under nitrogen starvation conditions, reaching 39% of dry cell weight, with the proportion of oleic acid (18:1) and linoleic acid (18:2) reaching 54% of total fatty acids. Taken together, these results indicate that the newly identified Chlorella species, ArM0029B, is a promising candidate for biodiesel production.

A fed-batch process for the production of biosimilar monoclonal antibody was developed. Since the brand product is produced by perfusion process, the impact of process change from perfusion to fed-batch on product quality and cell performance was evaluated. Perfusion culture was performed at 0.47–1.00 (v/v/d) perfusion rate by spin-filter method with 15–17 μm mesh. Culture parameters such as pH (6.8–7.2), dissolved oxygen (40–70% air saturation), temperature (37 °C) and agitation speed (250 rpm) were applied in both culture modes. In terms of cell performance, volumetric productivity increased 3.7 times while process performance increased 7.5 times in fed-batch culture due to 10 times higher scalability. Considering the glycosylation pattern and charge variants, no significant changes in product quality were observed upon process change, although intact IgG level slightly decreased in fed-batch mode. The change of production media showed more effect on glycosylation patterns than the operation in different culture modes. Furthermore, there were no differences in biological activity, including TNFα, FcγRIIIa, and C1q-binding affinity. Through a scale-up study from 3 L to 12,500 L, it was confirmed that cell performance and product quality could be maintained. In conclusion, product quality of the fed-batch process was comparable to that of the reference product.

Histone deacetylases (HDACs) play a crucial role in tumorigenesis. Over-expression of HDACs has been reported in lung cancer. The mechanism of highly expressed HDAC1 in lung cancer has yet not been determined. In the present study, we showed that miR-449a/b regulates HDAC1 by directly binding with the 3' untranslated region of the HDAC1. The expression of miR-449a/b was down-regulated and the expression of HDAC1 was up-regulated in primary lung cancer. The down expression of miR-449a/b might be one mechanism for over-expression of HDAC1 in lung cancer. miR-449a/b inhibited cell growth and anchorage-independent growth. Furthermore, co-treatment with miR-449a and HDAC inhibitors had a significant growth reduction compared with HDAC inhibitor mono-treatment. These results suggest that miR-449a/b may have a tumor suppressor function and might be a potential therapeutic candidate in patients with primary lung cancer.

Macrophage colony-stimulating factor (M-CSF) stimulation results in the production of reactive oxygen species (ROS) that participate in the proliferation of monocyte/macrophage. However, the molecular mechanisms whereby ROS modulate the signaling processes of M-CSF remain poorly defined. We report here that the redox-sensitive Src homology region 2 domain-containing phosphatase 1 (SHP1) is a critical regulator of M-CSF-mediated signaling in bone marrow monocyte/macrophage lineage cells (BMMs). Application of diphenylene iodonium (DPI) inhibited the responses of BMMs to M-CSF, including ROS production, cell proliferation, and phosphorylation of c-Fms as well as Akt kinase, but not of MAP kinases such as ERK, p38, and JNK. Dysregulation of SHP1 by overexpression or RNA interference in BMMs showed that SHP1 specifically regulates PI3 kinase (PI3K)/Akt signaling, but not MAP kinases in a redox-dependent manner, thereby regulating proliferation of BMMs through cyclins D1 and D2. These findings demonstrate that M-CSF-mediated ROS generation leads to SHP1 oxidation, which promotes cell proliferation through the PI3K/Akt-dependent signaling pathway.

The point spread function (PSF) plays an important role in electron beam (e-beam) lithography, e.g., estimation of resist profile, proximity effect correction, etc. One of the essential tasks is how to estimate the PSF with accuracy and efficiency. Conventional approaches include estimation of PSF's based on certain functions or through a Monte Carlo simulation. A new approach to estimating PSF's based on experimental data is proposed to provide an alternative to the conventional approaches. It utilizes the relationship between a PSF and a line spread function (LSF), and that between a LSF and the remaining resist profile. Since effects of all phenomena and processes involved in the exposure step are reflected in experimental results, the proposed approach has a good potential to generate realistic PSF's for any substrates and e-beam tools as long as experiments can be carried out. In this paper, the implementation of the new approach for estimation of the forward scattering part of PSF is described along with the simulation and experiment results.

One of the essential tasks in the dose control for fabrication of 2-D and 3-D patterns using electron-beam lithography is estimation of remaining resist profiles after development. A conventional approach is to compute the exposure distribution for a target pattern through convolution with the point spread function (PSF) and then obtain the resist profile via simulation of the development process based on the exposure distribution. A new approach which does not require calculation of the exposure distribution and simulation of the resist development is proposed. It utilizes a set of experimental results on which estimation of the resist profile is based, and has a good potential to provide an alternative to the conventional approaches. In this paper, the proposed approach is described in detail along with the results obtained from an extensive simulation and also experiments.

We demonstrate the cytotoxic potential of the Schiff base iron complex [Fe III (salophene)Cl] in vitro and ex vivo and illustrate its ability to overcome multiple drug resistance in vincristine and daunorubicine resistant leukemic cells (Nalm-6). Treatment of lymphoma cells (BJAB) with [Fe III (salophene)Cl] led to the exclusion of unspecific necrosis, a concentration-dependent inhibition of proliferation and a specific apoptotic cell death. We further detected a significant loss of the mitochondrial membrane potential in lymphoma cells and an up- and downregulation of various apoptosis relevant genes, respectively, indicating the involvement of the intrinsic mitochondrial pathway.

This randomized trial enrolled 442 infants in the Republic of Korea to assess the immunogenicity and safety of a combined diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine (DTaP-IPV; Tetraxim™) for primary vaccination at 2, 4 and 6 months of age compared with DTaP and IPV vaccines given separately. Immunogenicity was high in both groups; seroprotection and seroconversion rates of the combined vaccine (Group A) were non-inferior to the control vaccines (Group B). All subjects were seroprotected against poliovirus types 1, 2 and 3 (≥ 81/dil) and anti-diphtheria (≥ 0.01 IU/mL); 99.0% were seroprotected against tetanus (≥ 0.1 IU/mL). At least 93.6% had anti-diphtheria antibody titers ≥ 0.1 IU/mL. Anti-pertussis toxoid (PT) and anti-filamentous haemagglutinin (FHA) seroconversion (≥ 4-fold increase in antibody titer) rates were 96.6% and 94.4% for Group A, 92.2% and 78.4% for Group B. Most solicited reactions occurred within 4 days of vaccination, resolved within 3 days and were mild. Severe solicited reactions occurred after ≤ 0.5% of doses in Group A and ≤ 0.9% in Group B. No withdrawals occurred because of adverse events. The DTaP-IPV combined vaccine given at 2, 4, and 6 months of age was well tolerated; immunogenicity was similar to the control vaccines.

The flow pattern of the refrigerant in an evaporator-inlet pipe is a very important factor for determining the type of refrigerant-induced noise because the shape and size of the bubble are different according to the flow pattern in the pipe. In this study, the relations between refrigerant-induced noise and flow patterns are discussed. The flow patterns of the fluid in horizontal and vertical pipes were also estimated using Hewitt, Taitel-Dukler and Oshinowo-Charles maps. The refrigerant-supplying equipment was used to monitor the characteristics of the flow in the experiments. The shape and layout of evaporator-inlet pipe were suggested not to be the intermittent flow pattern. The noise level radiated from the refrigerator could be reduced by about 2-5 dB in the frequency range from 315 Hz to 3.15 kHz.

Uniform filter bank approach can be considered to perform independent component analysis (ICA) for convolved mixtures. It achieves better separation performance than the frequency domain approach and gives faster convergence speed with less computational complexity than the time domain approach. However, when the uniform filter bank approach is applied to natural audio signals, it provides slower convergence for low frequency subbands and gives inferior separation performance for high frequency subbands. Owing to spectral characteristics of natural signals, we present a filter bank approach that employs a Bark-scale filter bank. In the Bark-scale filter bank, low frequency region is minutely divided, whereas high frequency region has much wider subbands. The Bark-scale filter bank approach shows faster convergence speed than the uniform filter bank approach because it has more whitened inputs in the low frequency subbands. It also improves the separation performance as it has enough data to train adaptive parameters exactly in the high frequency subbands.

In this work, biotinylated gradient polyethylene (PE) surface was designed to bind a Q-dot streptavidin. Firstly, gradient PE surface was prepared by increasing corona treatment along the PE length. The gradient surface was treated with polyethyleneimine and then biotin. The biotinylated gradient PE surface gave Q-dot-modified gradient PE surface through binding of Q-dot streptavidin with biotinylated gradient PE surface. Q-dot-modified gradient PE surface displayed red fluorescence upon photoirradiation. The red fluorescence that corresponded to a Q-dot streptavidin on the biotinylated gradient PE surface increased gradually on the surface along the PE length. We believed that Q-dot-modified gradient PE surfaces might be applied as a nanotechnology analysis tool in the biomedical application.

In this work, we prepared nano-emulsified paclitaxel using administration form of the self-microemulsifying drug delivery systems (SMEDDS) in order to increase efficacy of paclitaxel. As paclitaxel delivery carrier, we chose MPEG–PLGA diblock copolymers with different hydrophilic and hydrophobic balances (HLB) by changing PLGA segments under constant MPEG segment. Paclitaxel and MPEG–PLGA diblock copolymers were dissolved by solubilizer such as tetraglycol, Cremophor ELP, and Labrasol. The droplet size for all formulations of nano-emulsified paclitaxel was found in the range of 200–300 nm by dynamic light scattering. The prepared SMEDDS showed a spherical shape of nano-emulsion. The storage stability of the nano-emulsified paclitaxels depended on HLB values of MPEG–PLGA diblock copolymers. In conclusion, we confirmed that the formulations tried in this study could be used as administration form of paclitaxel.

In many applications such as optoelectronic devices, three-dimensional (3D) structures are required. Examples include photonic band gap (PBG) crystals, diffractive optical elements, blazed gratings, MEMS, NEMS, etc. It is known that the performance characteristics of such structures are highly sensitive to their dimensional fidelity. Therefore, it is essential to have a fabrication process by which such 3D structures can be realized with high dimensional accuracy. In this paper, practical methods to control thickness of the remaining resist and etch depth, which may be employed for fabrication of such 3D structures using grayscale electron-beam lithography, are described. Through experiments, explicit control of the remaining resist thickness and etch depth at the resolution of 20nm for the feature sizes of 0.5@mm and 1@mm has been successfully demonstrated. Also, the 1:1 ratio of silicon to resist etching rates was achieved for transferring the remaining resist profile onto the silicon substrate.

House dust mites, Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus , are major allergens in the most common indoor allergen and are important risk factor for asthma. The modified antigen has been studied to treat allergic disorder. This study was carried out to measure possibility of modified allergen using gamma irradiation to treat allergy such as asthma. DF solutions (2 mg/ml) as target allergen were irradiated with Co-60 at 50 and 100 kGy. Conformational alternation of irradiated DF was observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Levels of anti-irradiated DF mouse IgGs (sub-isotypes) against intact DF were measured similar to that of anti-intact DF IgGs. The binding abilities of house dust mite-allergic patients’ IgE were reduced depending on radiation dose, and irradiation could inhibit the binding ability of patients’ IgE more than 40%. This study has shown that the binding ability of IgE was reduced by conformational alteration by irradiation and the irradiated DF had epitopes capable to induce immunogeniciy.

The study was conducted to compare the radiation types of a gamma ray and an electron beam for the inhibition and reduction of a food allergy. OVA (2 mg/ml) were irradiated at 3, 5, 7 and 10 kGy. Patterns detected by the SDS-PAGE and an immunoblot showed that the intact OVA band disappeared and that it was dependant upon the radiation doses regardless of the radiation types. Binding abilities of the irradiated OVA against the monoclonal IgG and the egg allergic patients’ IgE decreased due to a conformational change of the epitope, but differences from using the two different radiation types were not observed. The results indicate that both the radiation types can be used for an inhibition and a reduction of a food allergy regardless of the radiation types.