Fluidic self-assembly for MicroLED displays by controlled viscosity.

Displays in which arrays of microscopic 'particles', or chiplets, of inorganic light-emitting diodes (LEDs) constitute the pixels, termed MicroLED displays, have received considerable attention1,2 because they can potentially outperform commercially available displays based on organic LEDs3,4 in terms of power consumption, colour saturation, brightness and stability and without image burn-in issues1,2,5-7. To manufacture these displays, LED chiplets must be epitaxially grown on separate wafers for maximum device performance and then transferred onto the display substrate. Given that the number of LEDs needed for transfer is tremendous-for example, more than 24 million chiplets smaller than 100 µm are required for a 50-inch, ultra-high-definition display-a technique capable of assembling tens of millions of individual LEDs at low cost and high throughput is needed to commercialize MicroLED displays. Here we demonstrate a MicroLED lighting panel consisting of more than 19,000 disk-shaped GaN chiplets, 45 µm in diameter and 5 µm in thickness, assembled in 60 s by a simple agitation-based, surface-tension-driven fluidic self-assembly (FSA) technique with a yield of 99.88%. The creation of this level of large-scale, high-yield FSA of sub-100-µm chiplets was considered a significant challenge because of the low inertia of the chiplets. Our key finding in overcoming this difficulty is that the addition of a small amount of poloxamer to the assembly solution increases its viscosity which, in turn, increases liquid-to-chiplet momentum transfer. Our results represent significant progress towards the ultimate goal of low-cost, high-throughput manufacture of full-colour MicroLED displays by FSA.

Identification of peptide inhibitors of matrix metalloproteinase 1 using an in-house assay system for the enzyme.

Matrix metalloproteinases (MMPs) are zinc-dependent proteases involved in the degradation of extracellular matrix proteins. As one of the isoforms, MMP-1 breaks down collagen, and its activity is known to be important in wound healing. Its timely and adequate level of expression is pivotal because MMP-1 is also involved in the damage or aging of skins as well as in certain types of cancers. Thus, both assaying the MMP-1 activity and developing its inhibitors are of great importance. We here developed an in-house assay system that gave us the high degree of freedom in screening peptide inhibitors of MMP-1. The assay system utilized a circularly permutated fusion of ß-lactamase and its inhibitory protein through an MMP-1-sensitive linker so that the activity of MMP-1 could be translated into that of ß-lactamase. As a proof of concept, we applied the developed assay system to initial screens of MMP-1 inhibitors and successfully identified one lead peptide that inhibited the collagenase activity of the enzyme.

Inhibitory Effects of Novel SphK2 Inhibitors on Migration of Cancer Cells.

BACKGROUND: Cell migration is an essential process for survival and differentiation of mammalian cells. Numerous diseases are induced or influenced by inappropriate regulation of cell migration, which plays a key role in cancer cell metastasis. In fact, very few anti-metastasis drugs are available on the market. SphKs are enzymes that convert sphingosine to sphingosine-1-phosphate (S1P) and are known to control various cellular functions, including migration of cells. In human, SphK2 is known to promote apoptosis, suppresses cell growth, and controls cell migration; in addition, the specific ablation of SphK2 activity was reported to inhibit cancer cell metastasis. OBJECTIVE: The previously identified SG12 and SG14 are synthetic analogs of sphingoid and can specifically inhibit the functions of SphK2. We investigated the effects of the SphK2 specific inhibitors on the migratory behavior of cells. METHOD: We investigated how SG12 and SG14 affect cell migration by monitoring both cumulative and individual cell migration behavior using HeLa cells. RESULTS: SG12 and SG14 mutually showed stronger inhibitory effects with less cytotoxicity compared with a general SphK inhibitor, N,N-dimethylsphingosine (DMS). The mechanistic aspects of specific SphK2 inhibition were studied by examining actin filamentation and the expression levels of motility-related genes. CONCLUSION: The data revealed that SG12 and SG14 resemble DMS in decreasing overall cell motility, but differ in that they differentially affect motility parameters and motility-related signal transduction pathways and therefore actin polymerization, which are not altered by DMS. Our findings show that SphK2 inhibitors are putative candidates for anti-metastatic drugs.

Cone beam CT findings of retromolar canals: Report of cases and literature review.

A retromolar canal is an anatomical variation in the mandible. As it includes the neurovascular bundle, local anesthetic insufficiency can occur, and an injury of the retromolar canal during dental surgery in the mandible may result in excessive bleeding, paresthesia, and traumatic neuroma. Using imaging analysis software, we evaluated the cone-beam computed tomography (CT) images of two Korean patients who presented with retromolar canals. Retromolar canals were detectable on the sagittal and cross-sectional images of cone-beam CT, but not on the panoramic radiographs of the patients. Therefore, the clinician should pay particular attention to the identification of retromolar canals by preoperative radiographic examination, and additional cone beam CT scanning would be recommended.

Comparison of conventional lateral cephalograms with corresponding CBCT radiographs.

PURPOSE: This study was performed to assess the compatibility of cone beam computed tomography (CBCT) synthesized cephalograms with conventional cephalograms, and to find a method for obtaining normative values for three-dimensional (3D) assessments. MATERIALS AND METHODS: The sample group consisted of 10 adults with normal occlusion and well-balanced faces. They were imaged using conventional and CBCT cephalograms. The CBCT cephalograms were synthesized from the CBCT data using OnDemand 3D software. Twenty-one angular and 12 linear measurements from each imaging modality were compared and analyzed using paired-t test. RESULTS: The linear measurements between the two imaging modalities were not statistically different (p>0.05) except for the U1 to facial plane distance. The angular measurements between the two imaging modalities were not statistically different (p>0.05) with the exception of the gonial angle, ANB difference, and facial convexity. CONCLUSION: Two-dimensional cephalometric norms could be readily used for 3D quantitative assessment, if corrected for lateral cephalogram distortion.

Dose evaluation of selective collimation effect in cephalography by measurement and Monte Carlo simulation.

Recently, simulations based on the Monte Carlo code have been increasingly applied for physics phenomena, patient dose and quality assurance of radiation systems. The objective of this study was to use Monte Carlo simulation and measurement to verify dose and dose reduction in cephalography. The collimator was constructed with 3-mm thick lead plate, and attached to the tube head to remove regions of disinterest in the radiation field. A digital phantom patient was constructed to evaluate patient dose. In addition, detectors of pixel size 1×1 cm² and 0.1×0.1 cm² were constructed to check collimator location. The effective dose according to International Commission on Radiological Protection 103 was calculated with and without collimation. The effective doses for simulation with and without collimation were 5.09 and 11.32 µSv, respectively. The results of the calculated effective dose show 61.7 % reduction of field area and 55 % of effective dose. The Monte Carlo simulation is a good evaluation tool for patient dose.

Dose area product measurement for diagnostic reference levels and analysis of patient dose in dental radiography.

In this study, diagnostic reference levels (DRLs) were suggested and patient doses were analysed through the dose-area product value in dental radiography. In intraoral radiography, at three sites, i.e. molar, premolar and incisor on the maxilla and acquired third quartile values: 55.5, 46 and 36.5 mGy cm(2), respectively, were measured. In panoramic, cephalometric and cone beam computed tomography, the values were 120.3, 146 and 3203 mGy cm(2) (16 × 18 cm), respectively. It has been shown that, in intraoral radiography, the patient dose changes proportionally to the value of mA s, but the change in extraoral radiography in response to mA s could not be confirmed. The authors could confirm, however, the difference in dose according to the manufacturer in all dental radiography examinations, except for panoramic radiography. Depending on the size of hospital, there were some differences in patient dose in intraoral radiography, but no difference in patient dose in extraoral radiography.

Identification of immunological parameters associated with the alveolar bone level in periodontal patients.

PURPOSE: The present study was performed to clarify the relationship between periodontal disease severity and selected immunological parameters consisting of serum IgG titer against periodontopathogenic bacteria, the expression of the helper T-cell cytokine by gingival mononuclear cells, and patients' immunoreactivity to cross-reactive heat shock protein (HSP) epitope peptide from P. gingivalis HSP60. METHODS: Twenty-five patients with moderate periodontitis had their gingival connective tissue harvested of gingival mononuclear cells during an open flap debridement procedure and peripheral blood was drawn by venipuncture to collect serum. The mean level of interproximal alveolar bone was calculated to be used as an index for periodontal disease severity for a given patient. Each of selected immunologic parameters was subject to statistical management to seek their correlations with the severity of periodontal disease. RESULTS: A significant correlation could not be identified between serum IgG titers against specific bacteria (Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, and Streptococcus mutans) and the severity of periodontal disease. Expression of interleukin (IL)-10 by gingival mononuclear cells was statistically significant in the group of patients who had higher levels of alveolar bone height. However, a similar correlation could not be demonstrated in cases for IL-4 or interferon-gamma. Patients' serum reactivity to cross-reactive epitope peptide showed a significant correlation with the amount of alveolar bone. CONCLUSIONS: It was concluded that expression of IL-10 by gingival mononuclear cells and patients' sero-reactivity to the cross-reactive HSP peptide of P. gingivalis HSP60 were significantly correlated with alveolar bone height.

Fermented rice bran downregulates MITF expression and leads to inhibition of alpha-MSH-induced melanogenesis in B16F1 melanoma.

Rice bran contains various polyphenolic compounds with anti-oxidative activities, and it has long been known to inhibit melanogenesis, but the inhibition mechanism has not been fully elucidated. Cofermentation of rice bran with Lactobacillus rhamnosus and Saccharomyces cerevisiae significantly reduced the cytotoxicity of the resulting extract to B16F1 melanoma cells. Marked reduction of alpha-melanocyte stimulating hormone (MSH) induced melanin synthesis was also observed upon treatment with fermented rice bran extract but it had no direct inhibitory effect on tyrosinase activity, while the intracellular tyrosinase activity was reduced by the extract. This result was further confirmed by an immunoblot assay measuring the level of tyrosinase protein. In addition, the expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanogenesis, was significantly decreased by the extract. All together, the fermented rice bran extracts showed an inhibitory effect on melanogenesis through downregulation of MITF, along with reduced cytotoxicity.

Anti-aging effect of rice wine in cultured human fibroblasts and keratinocytes.

The application of rice wine on skin is known to have beneficial effects such as enhancement of the skin barrier function and skin whitening. In this study, we focused on examination of the anti-aging effects of rice wine. The treatment of fibroblasts with rice wine in vitro increased the expression of procollagen and laminin-5, a key basement membrane component in cultured human fibroblasts. Rice wine significantly reduced the expression of UV-induced matrix metalloproteinase-1 (MMP-1) in a dose-dependent manner in both cultured human fibroblasts and keratinocytes. In addition, treatment with rice wine decreased UV-induced tumor necrosis factor-alpha (TNF-alpha) production in human keratinocytes. An in vivo study using hairless mice showed that topical application of rice wine protected mouse skin from photoaging. Thus, we suggest that rice wine may have potential as an effective agent for the prevention and treatment of UV-induced skin aging.

Phosphatidylserine prevents UV-induced decrease of type I procollagen and increase of MMP-1 in dermal fibroblasts and human skin in vivo.

In an effort to find topical agents that prevent or retard cutaneous aging, seven functional lipids were screened for their procollagen-upregulating and matrix metalloproteinase (MMP)-1-downregulating activities in human dermal fibroblasts by Western blotting. The preventive effect on ultraviolet (UV)-induced decrease of procollagen was demonstrated in phosphatidylserine (PS), lysophosphatidylserine (LPS), lysophosphatidic acid (LPA), N-acetyl phytosphingosine (NAPS), and tetraacetyl phytosphingosine (TAPS). Furthermore, PS, LPS, and LPA upregulated procollagen expression in unirradiated basal conditions. The inhibitory effect on UV-induced MMP-1 expression was seen in NAPS, TAPS, LPA, PS, lysophosphatidylglycerol, and LPS. PS was chosen as the most suitable candidate anti-aging chemical for the subsequent in vivo studies. We investigated the effects of PS on acute UV response and chronologic skin aging by topically applying it to young skin before UV irradiation and to aged human skin, respectively. Real-time PCR and Western blot revealed that in the young skin, PS treatment prevented UV-induced reduction in procollagen expression and inhibited UV-induced MMP-1 expression. PS also blocked UV-induced IL-6 and COX-2 gene expression in cultured fibroblasts dose-dependently. In the aged skin, PS caused increased procollagen transcription and procollagen immunostaining in the upper dermis, and a significant decrease in MMP-1 expression at both mRNA and protein levels. These results indicate that topical PS has anti-skin-aging properties and point to the potential use of PS as a therapeutic agent in the prevention and treatment of cutaneous aging.

Suppression of mast cell degranulation by a novel ceramide kinase inhibitor, the F-12509A olefin isomer K1.

Antigen-induced degranulation of mast cells plays a pivotal role in allergic and inflammatory responses. Recently, ceramide kinase (CERK) and its phosphorylated product ceramide 1-phosphate (C1P) have emerged as important players in mast cell degranulation. Here, we describe the synthesis of a novel F-12509A olefin isomer, K1, as an effective CERK inhibitor. In vitro kinase assays demonstrated that K1 effectively inhibits CERK without inhibiting sphingosine kinase and diacylglycerol kinase. Treating RBL-2H3 cells with K1 reduced cellular C1P levels to 40% yet had no effect on cell growth. Furthermore, treatment with K1 significantly suppressed both calcium ionophore- and IgE/antigen-induced degranulation, indicating that K1 interferes with signals that happen downstream of Ca(2+) mobilization. Finally, we show that K1 affects neither IgE/antigen-induced global tyrosine phosphorylation nor subsequent Ca(2+) elevation, suggesting a specificity for CERK-mediated signals. Our novel CERK inhibitor provides a useful tool for studying the biological functions of CERK and C1P. Moreover, to our knowledge, this is the first report demonstrating that inhibition of CERK suppresses IgE/antigen-induced mast cell degranulation. This finding suggests that CERK inhibitors might be a potential therapeutic tool in the treatment of allergic diseases.

High-level production of arachidonic acid by fed-batch culture of Mortierella alpina using NH4OH as a nitrogen source and pH control.

Mortierella alpina was grown in a fed-batch culture using a 12-l jar fermenter with an initial 8-l working volume containing 20 g glucose l-1 and 10 g corn-steep powder l-1. Glucose was intermittently fed to give 32 g l-1 at each time. The pH of culture was maintained using 14% (v/v) NH4OH, which also acted as a nitrogen source. A final cell density of 72.5 g l-1 was reached after 12.5 days with a content of arachidonic acid (ARA) at 18.8 g l-1. These values were 4 and 1.8 times higher than the respective values in batch culture. Our results suggest that the combined feeding of glucose and NH4+ to the growth of M. alpina could be applied for the industrial scale production of ARA.

Synthesis and evaluation of sphingoid analogs as inhibitors of sphingosine kinases.

Sphingosine 1-phosphate (S1P), a product of sphingosine kinases (SphK), mediates diverse biological processes such as cell differentiation, proliferation, motility, and apoptosis. In an effort to search and identify specific inhibitors of human SphK, the inhibitory effects of synthetic sphingoid analogs on kinase activity were examined. Among the analogs tested, we found two, SG12 and SG14, that have specific inhibitory effects on hSphK2. N,N-Dimethylsphingosine (DMS), a well-known SphK inhibitor, displayed inhibitory effects for both SphK1 and SphK2, as well as protein kinase C. In contrast, SG12 and SG14 exhibited selective inhibitory effects on hSphK2. Furthermore, SG14 did not affect PKC. In isolated platelets, SG14 blocked the conversion of sphingosine into sphingosine 1-phosphate significantly. This is the first report on the identification of a hSphK2-specific inhibitor, which may provide a useful tool for studying the biological functions of hSphK2.

Cloning and functional characterization of the SUR2/SYR2 gene encoding sphinganine hydroxylase in Pichia ciferrii.

Saccharomyces cerevisiae sphinganine C4-hydroxylase encoded by the SUR2 gene catalyses the conversion of sphinganine to phytosphingosine. We isolated the SUR2 gene from Pichia ciferrii using nucleotide sequence homology to S. cerevisiae SUR2 to study hydroxylation of sphinganine in the sphingoid base overproducing yeast P. ciferrii. A positive clone was confirmed by nucleotide sequencing. A syringomycin-E resistance phenotype of a S. cerevisiae sur2-null mutant was complemented by expression of the cloned P. ciferrii SUR2 gene. Restoration of phytosphingosine production in the complemented strain was also confirmed, indicating that the cloned gene is a functional homologue of S. cerevisiae SUR2. .

Personal computer-based three-dimensional computed tomographic images of the teeth for evaluating supernumerary or ectopically impacted teeth.

This study describes the use of personal computer (PC)-based three-dimensional computed tomographic (3D CT) images in the evaluation of supernumerary and ectopically impacted teeth. Three selected cases were presented as examples of the more complex cases in which 3D CT imaging added information not readily available from periapical, occlusal, or panoramic radiographs. Patients were CT scanned from the occlusal plane to the periapical region of the impacted teeth. Digital Image and Communications in Medicine CT data were transferred to a personal laptop computer using a network line. 3D volume rendering was performed using PC-based volumetric analysis software. 3D CT-reformatted imaging of the teeth is a useful way to investigate and localize supernumerary or impacted teeth. Newer software that enables this investigation using a PC provides a relatively inexpensive way to carry out such investigations, making it easier for dental practitioners to request such investigations and to view the results in real time in their own offices.

Effect of mandibular positioning on preimplant site measurement of the mandible in reformatted CT.

The purpose of this study was to evaluate the effect of mandibular positioning on measurement of the reformatted cross-sectional image of the mandible in computed tomography (CT) according to the area on the mandible. Five dried mandibles, partially edentulous in the premolar and molar areas, were selected. The inferior border of the mandible was placed at 0-, 5-, 10-, 15-, and 20-degree angles to the CT scanning plane, and CTs were taken. The marked area of the reformatted cross-sectional image taken at each angle was found, and the distance from the most superior border of the mandibular canal to the alveolar crest was measured. As the angle between the CT scanning plane and mandibular plane increased, the distance from the most superior border of the mandibular canal to the alveolar crest also increased. The degree of increase was more pronounced in the posterior portion of the mandible than in the anterior portion of the mandible. As mandibular positional change in the CT gantry can affect the vertical measurement of the reformatted cross-sectional image, a correct guiding plane is necessary to accurately position the jaw to the CT scanning plane.

Integrative transformation system for the metabolic engineering of the sphingoid base-producing yeast Pichia ciferrii.

We have developed an integrative transformation system for metabolic engineering of the tetraacetyl phytosphingosine (TAPS)-secreting yeast Pichia ciferrii. The system uses (i) a mutagenized ribosomal protein L41 gene of P. ciferrii as a dominant selection marker that confer resistance to the antibiotic cycloheximide and (ii) a ribosomal DNA (rDNA) fragment of P. ciferrii as a target for multicopy gene integration into the chromosome. A locus within the nontranscribed region located between 5S and 26S rDNAs was selected as the integration site. A maximum frequency of integrative transformation of approximately 1,350 transformants/ microg of DNA was observed. To improve the de novo synthesis of sphingolipid, the LCB2 gene, encoding a subunit of serine palmitoyltransferase, which catalyzes the first committed step of sphingolipid synthesis, was cloned from P. ciferrii and overexpressed under the control of the P. ciferrii glyceraldehyde-3-phosphate dehydrogenase promoter. After transformation of an LCB2 gene expression cassette, several transformants that contained approximately five to seven copies of transforming DNA in the chromosome and exhibited about 50-fold increase in LCB2 mRNA relative to the wild type were identified. These transformants were observed to produce approximately two times more TAPS than the wild type.