Effect of Coating Thickness on Abrasion and Cutting Performance of NCD-Coated Ball Endmills on Graphite Machining.

Nano-crystalline diamond (NCD) coating to improve the performance of cutting tools, as the coating thickness varies, the cutting performance and lifespan of the tool varies because the radius of its cutting edge and coating surface roughness are altered. Therefore, an in-depth analysis on the impact of the variations in coating thickness on the cutting tool abrasion and quality of machined surface is necessary. In this study, two NCD ball endmills were coated with 8 and 12 µm thicknesses, and the tool abrasion and roughness of the machined plane were observed after milling. Furthermore, the morphology of the coated surface and abrased cutting edge were observed using a 3D confocal microscope. Consequently, we observed that individual nodules were formed on the continuous aggregates as the coating thickness increased, which increased the coated surface roughness. The two damage modes of the aggregation determined the dominant abrasion that occurred on the cutting edges of both types of coating thicknesses. Delamination and crater wear caused a sharp increase in the roughness of the machined surface. In summary, the increase in coating thickness delayed the delamination of the coating but increased the roughness of the cutting edge, which reduced the machined surface roughness.

Deep learning-based framework for slide-based histopathological image analysis.

Digital pathology coupled with advanced machine learning (e.g., deep learning) has been changing the paradigm of whole-slide histopathological images (WSIs) analysis. Major applications in digital pathology using machine learning include automatic cancer classification, survival analysis, and subtyping from pathological images. While most pathological image analyses are based on patch-wise processing due to the extremely large size of histopathology images, there are several applications that predict a single clinical outcome or perform pathological diagnosis per slide (e.g., cancer classification, survival analysis). However, current slide-based analyses are task-dependent, and a general framework of slide-based analysis in WSI has been seldom investigated. We propose a novel slide-based histopathology analysis framework that creates a WSI representation map, called HipoMap, that can be applied to any slide-based problems, coupled with convolutional neural networks. HipoMap converts a WSI of various shapes and sizes to structured image-type representation. Our proposed HipoMap outperformed existing methods in intensive experiments with various settings and datasets. HipoMap showed the Area Under the Curve (AUC) of 0.96±0.026 (5% improved) in the experiments for lung cancer classification, and c-index of 0.787±0.013 (3.5% improved) and coefficient of determination ([Formula: see text]) of 0.978±0.032 (24% improved) in survival analysis and survival prediction with TCGA lung cancer data respectively, as a general framework of slide-based analysis with a flexible capability. The results showed significant improvement comparing to the current state-of-the-art methods on each task. We further discussed experimental results of HipoMap as pathological viewpoints and verified the performance using publicly available TCGA datasets. A Python package is available at https://pypi.org/project/hipomap , and the package can be easily installed using Python PIP. The open-source codes in Python are available at: https://github.com/datax-lab/HipoMap .

Two-Step Glass Molding Process for Forming Glass Edges with Obtuse Angles for Mobile Displays.

The domain of edge displays with 2.5D or 3D curved designs has been expanded to improve user convenience. The currently available 3D cover glass offers a limited curvature radius of at least 5 mm and a curvature less than 88°, due to limitations in the undercuts and formability of parts. The development of a full 3D cover, applicable to next-generation displays, requires cover glass molding technology with a curvature exceeding 90°. Here, a mold design and molding process, which addresses the current limitations by dividing the existing glass molding press (GMP) process into two stages, is proposed. The bending geometry of the glass prepared on the basis of the proposed mold design plan during single-step compression forming and two-step compression forming was predicted using commercial analysis software. A molding product with a curvature radius of 2.5 mm and an angle of curvature of 138.9° was produced when process conditions with bending by up to 180° with no damage were applied during actual forming experiments. Further research on annealing and cooling processes of GMP is expected to enable the design and process implementation to manufacture curved glass with a single curvature of at least 90° and multiple curvatures.

Analysis of Tool Wear and Roughness of Graphite Surfaces Machined Using MCD and NCD-Coated Ball Endmills.

The high-purity G5 graphite material is widely used for glass moulding and provides high hardness and brittleness because it is sintered to fine particles unlike other graphite materials. Hence, tool cutting of a G5 workpiece is performed by local fracture instead of plastic deformation of the machined surface. Although a diamond-coated tool with outstanding hardness is used to machine very hard graphite, the tool shows variability regarding the service life and machining performance depending on the grain size, even in the same machining environment. We investigated the wear and change trend of machined surface roughness considering microcrystalline diamond (MCD) and nanocrystalline diamond (NCD)-coated tools, which are generally used to machine graphite materials, and analysed their relation with coating. For rough machining, the MCD-coated tool, for which the delamination of coating occurred later, showed less wear and improved machined surface roughness. For precision machining, the NCD tool showed less tool wear rate relative to the cutting length, leading to a small difference in the machined surface roughness between the two tools. We conclude that if rough and precision machining processes are performed using the same cutting tool, the MCD-coated tool is advantageous in terms of service life, while the difference in roughness of the final machined surface between the tools is negligible.

Non-thermal atmospheric pressure plasma induces epigenetic modifications that activate the expression of various cytokines and growth factors in human mesoderm-derived stem cells.

Non-thermal atmospheric pressure plasma (NTAPP) has been reported to induce wound healing, activation of immune cells, and proliferation of mesoderm-derived adult stem cells in human. However, the mechanism by which NTAPP activates these physiological effects is poorly understood. Here, we examined whole genome expression profiles of adipose tissue-derived stem cells (ASCs), the proliferation of which is induced by NTAPP. NTAPP upregulated the expression of genes for cytokine and growth factor, but downregulated genes in apoptotic pathways. When ASCs were treated with NTAPP in the presence of a nitric oxide (NO) scavenger, the expression of various cytokines and growth factors decreased, suggesting that NO is primarily responsible for the enhanced cytokine and growth factor expression induced by NTAPP. Increased histone deacetyl transferase 1 (HDAC1) and decreased acetylated histone 3 were detected in NTAPP-treated ASCs. Similarly, ASCs pre-treated with HDAC, DNA methylation, or histone methylation inhibitors had reduced expression of cytokines and growth factors after NTAPP treatment. Taken together, these results strongly suggest that NTAPP induces epigenetic modifications that activate the expression of cytokines and growth factors, explaining how NTAPP acts as an efficient tool in regenerative medicine to stimulate stem cell proliferation, to activate immune cells, and to recover wounds.

Non-thermal atmospheric pressure plasma is an excellent tool to activate proliferation in various mesoderm-derived human adult stem cells.

Adult stem cells are capable of self-renewal and differentiation into specific cell types in tissues and have high potential for stem cell therapy. Mesenchymal and hematopoietic stem cells are easily attainable from the human body and have become applicable tools for adult stem cell therapy. However, there are still technical barriers for the application of mesenchymal and hematopoietic stem cells for therapy, such as the small number of cell populations, high risk of contamination, and loss of their stemness properties in vitro. In our previous study, we showed that non-thermal atmospheric pressure plasma (NTAPP) promoted the proliferation of adipose tissue-derived stem cells (ASCs) by 1.6-fold on average, while maintaining their stemness. Here, we examined the feasibility of NTAPP as a tool to activate the proliferation of mesenchymal and hematopoietic stem cells in vitro without affecting their stem cell characteristics. NTAPP increased the proliferation of bone marrow-derived stem cells (BM-MSCs) and hematopoietic stem cells (HSCs) by 1.8- and 2-fold, respectively, when compared to that of untreated cells. As observed in ASCs, NTAPP exposure also activated the expression of stem cell-specific surface markers, CD44 and CD105, by 5-fold in BM-MSCs, when compared to that in unexposed control cells in a low glucose medium with a low concentration of basic fibroblast growth factor (b-FGF). In addition, NTAPP exposure highly augmented the mRNA expression of well-known pluripotent genes for stemness, such as Oct4, Sox2, and Nanog in ASCs and BM-MSCs when compared to that in unexposed control cells. When cell cycle progression was examined, the G1-S shift was accelerated, and expression of PCNA was increased in NTAPP-exposed ASCs when compared to that in untreated control cells, suggesting that NTAPP activated G1-S transition. Taken together, these results demonstrated that NTAPP activated the proliferation of various mesodermal-derived human adult stem cells by accelerating the G1-S transition while maintaining their pluripotency and stemness, strongly suggesting that NTAPP can be an efficient tool for expanding the population of various adult stem cells in vitro for medical applications.

Effects of 1950 MHz radiofrequency electromagnetic fields on Aß processing in human neuroblastoma and mouse hippocampal neuronal cells.

Alzheimer's disease (AD) is a neurodegenerative disease leading to progressive loss of memory and other cognitive functions. One of the well-known pathological markers of AD is the accumulation of amyloid-beta protein (Aß), and its plaques, in the brain. Recent studies using Tg-5XFAD mice as a model of AD have reported that exposure to radiofrequency electromagnetic fields (RF-EMF) from cellular phones reduced Aß plaques in the brain and showed beneficial effects on AD. In this study, we examined whether exposure to 1950 MHz RF-EMF affects Aß processing in neural cells. We exposed HT22 mouse hippocampal neuronal cells and SH-SY5Y human neuroblastoma cells to RF-EMF (SAR 6 W/kg) for 2 h per day for 3 days, and analyzed the mRNA and protein expression of the key genes related to Aß processing. When exposed to RF-EMF, mRNA levels of APP, BACE1, ADAM10 and PSEN1 were decreased in HT22, but the mRNA level of APP was not changed in SH-SY5Y cells. The protein expression of APP and BACE1, as well as the secreted Aß peptide, was not significantly different between RF-EMF-exposed 7w-PSML, HT22 and SH-SY5Y cells and the unexposed controls. These observations suggest that RF-EMF exposure may not have a significant physiological effect on Aß processing of neural cells in the short term. However, considering that we only exposed HT22 and SH-SY5Y cells to RF-EMF for 2 h per day for 3 days, we cannot exclude the possibility that 1950 MHz RF-EMF induces physiological change in Aß processing with long-term and continuous exposure.

Non-Thermal Atmospheric Pressure Plasma Efficiently Promotes the Proliferation of Adipose Tissue-Derived Stem Cells by Activating NO-Response Pathways.

Non-thermal atmospheric pressure plasma (NTAPP) is defined as a partially ionized gas with electrically charged particles at atmospheric pressure. Our study showed that exposure to NTAPP generated in a helium-based dielectric barrier discharge (DBD) device increased the proliferation of adipose tissue-derived stem cells (ASCs) by 1.57-fold on an average, compared with untreated cells at 72 h after initial NTAPP exposure. NTAPP-exposed ASCs maintained their stemness, capability to differentiate into adipocytes but did not show cellular senescence. Therefore, we suggested that NTAPP can be used to increase the proliferation of ASCs without affecting their stem cell properties. When ASCs were exposed to NTAPP in the presence of a nitric oxide (NO) scavenger, the proliferation-enhancing effect of NTAPP was not obvious. Meanwhile, the proliferation of NTAPP-exposed ASCs was not much changed in the presence of scavengers for reactive oxygen species (ROS). Also, Akt, ERK1/2, and NF-κB were activated in ASCs after NTAPP exposure. These results demonstrated that NO rather than ROS is responsible for the enhanced proliferation of ASCs following NTAPP exposure. Taken together, this study suggests that NTAPP would be an efficient tool for use in the medical application of ASCs both in vitro and in vivo.

A Study on the Contaminant Dispersion from Isolation Ward under Abnormal Operation of Facilities.

Due to the recent outbreaks of infectious diseases, such as severe acute respiratory syndrome (SARS), Influenza and Ebola, isolation facilities have played an important role to prevent infectious diseases from spreading at initial stage. An isolation ward is a facility to isolate patients physically and to care them safely. One way to isolate a patient physically is to build a negative pressure isolation facility. However, unexpected failure or misuse of such facility makes it difficult to maintain negative pressure and eventually causes secondary infection, leaking the infectious pathogen to outside of the isolation ward. This study identifies the amount and velocity of leakage air from a patient ward by tracer gas experiment under abnormal operations of an isolation facility. In addition, computational fluid dynamics (CFD) allowed us to observe the outflow mechanism of pollutant. The results show that abnormal operations of a facility spreads pathogens to neighboring areas immediately and timely actions should be prepared against them.

A Protoberberine derivative HWY336 selectively inhibits MKK4 and MKK7 in mammalian cells: the importance of activation loop on selectivity.

A protoberberine derivative library was used to search for selective inhibitors against kinases of the mitogen-activated protein kinase (MAPK) cascades in mammalian cells. Among kinases in mammalian MAPK pathways, we identified a compound (HWY336) that selectively inhibits kinase activity of mitogen-activated protein kinase kinase 4 and 7 (MKK4 and MKK7). The IC50 of HWY336 was 6 µM for MKK4 and 10 µM for MKK7 in vitro. HWY336 bound to both kinases reversibly via noncovalent interactions, and inhibited their activity by interfering with access of a protein substrate to its binding site. The binding affinity of HWY336 to MKK4 was measured by surface plasmon resonance to determine a dissociation constant (Kd) of 3.2 µM. When mammalian cells were treated with HWY336, MKK4 and MKK7 were selectively inhibited, resulting in inhibition of c-Jun NH2-terminal protein kinases in vivo. The structural model of HWY336 bound to either MKK4 or MKK7 predicted that HWY336 was docked to the activation loop, which is adjacent to the substrate binding site. This model suggested the importance of the activation loop of MKKs in HWY336 selectivity. We verified this model by mutating three critical residues within this loop of MKK4 to the corresponding residues in MKK3. The mutant MKK4 displayed similar kinase activity as wild-type kinase, but its activity was not inhibited by HWY336 compared to wild-type MKK4. We propose that the specific association of HWY336 to the activation loop of MKK4/MKK7 is responsible for its selective inhibition.

Heritabilities of facial measurements and their latent factors in korean families.

Genetic studies on facial morphology targeting healthy populations are fundamental in understanding the specific genetic influences involved; yet, most studies to date, if not all, have been focused on congenital diseases accompanied by facial anomalies. To study the specific genetic cues determining facial morphology, we estimated familial correlations and heritabilities of 14 facial measurements and 3 latent factors inferred from a factor analysis in a subset of the Korean population. The study included a total of 229 individuals from 38 families. We evaluated a total of 14 facial measurements using 2D digital photographs. We performed factor analysis to infer common latent variables. The heritabilities of 13 facial measurements were statistically significant (p < 0.05) and ranged from 0.25 to 0.61. Of these, the heritability of intercanthal width in the orbital region was found to be the highest (h (2) = 0.61, SE = 0.14). Three factors (lower face portion, orbital region, and vertical length) were obtained through factor analysis, where the heritability values ranged from 0.45 to 0.55. The heritability values for each factor were higher than the mean heritability value of individual original measurements. We have confirmed the genetic influence on facial anthropometric traits and suggest a potential way to categorize and analyze the facial portions into different groups.