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This study investigated the effect of hydrogen (H) on the performance of amorphous In-Ga-Zn-Sn oxide (

This study examines the impact of channel length ( $L$ ) on the performance of amorphous In–Ga–Zn–O (a-IGZO) thin-film transistors with self-aligned structures. The negative threshold voltage ( ${V}_{\text{TH}}$ ) displacement for IGZO transistors with increasing drain voltage ( ${V}_{\text{DS}}$ ) becomes severe with decreasing ${L}$ from 10 to $2~ \mu \text{m}$ . The $V_{\text{DS}}$ -dependent negative $V_{\text{TH}}$ shift can be mitigated by increasing the oxygen flow rate (OFR) ratio during a-IGZO preparation from 40% to 80%, which suppresses the number of oxygen vacancy defects near the n+ drain of the a-IGZO region. In contrast, the hot carrier stress (HCS)-induced degradation in terms of the threshold voltage was accelerated for devices with increasing OFR ratio, presumably due to the creation of excessive oxygen-originated defects. The rationale for these observations is discussed with regard to the increasing local electric field near the drain junction, which was calculated by technology computer-aided design (TCAD) simulation. We concluded that an acceptable compromise between short channel effect and HCS-induced degradations can be achieved by choosing an intermediate OFR ratio of 64%.

We investigated the effect of film thickness (geometrical confinement) on the structural evolution of sputtered indium-zinc-tin oxide (IZTO) films as high mobility n-channel semiconducting layers during post-treatment at different annealing temperatures ranging from 350 to 700 °C. Different thicknesses result in IZTO films containing versatile phases, such as amorphous, low-, and high-crystalline structures even after annealing at 700 °C. A 19-nm-thick IZTO film clearly showed a phase transformation from initially amorphous to polycrystalline bixbyite structures, while the ultra-thin film (5 nm) still maintained an amorphous phase. Transistors including amorphous and low crystalline IZTO films fabricated at 350 and 700 °C show reasonable carrier mobility (µFE) and on/off current ratio (ION/OFF) values of 22.4–35.9 cm2 V−1 s−1 and 1.0–4.0 × 108, respectively. However, their device instabilities against positive/negative gate bias stresses (PBS/NBS) are unacceptable, originating from unsaturated bonding and disordered sites in the metal oxide films. In contrast, the 19-nm-thick annealed IZTO films included highly-crystalline, 2D spherulitic crystallites and fewer grain boundaries. These films show the highest µFE value of 39.2 cm2 V−1 s−1 in the transistor as well as an excellent ION/OFF value of 9.7 × 108. Simultaneously, the PBS/NBS stability of the resulting transistor is significantly improved under the same stress condition. This promising superior performance is attributed to the crystallization-induced lattice ordering, as determined by highly-crystalline structures and the associated formation of discrete donor levels (~ 0.31 eV) below the conduction band edge.

Background Evidence evaluating prescribing patterns in antibiotic (ABC) prophylaxis (PPX) for urology (UGY) procedures is limited. Although national guidelines give direction on the ABC PPX for specific procedures, ABC PPX should also be based on local ABC resistance patterns, individual host factors and procedure type factors. Our institution’s urine culture antibiogram illustrates increasing resistance to Cefazolin, a national guideline preferred ABC. The purpose of this study is to assess the impact of a quality improvement intervention on prescribing practices for ABC PPX in patients undergoing UGY procedures. Methods This is a retrospective study evaluating all patients receiving perioperative ABC PPX for UGY procedures from 01/01/2019 to 07/31/2019. The intervention (focusing on UGY provider education for ABC PPX based on local ABC resistance patterns, host factors and UGY procedure type) occurred on multiple in-person sessions during 04/2019. Emphasis occurred with replacing Cefazolin with Ceftriaxone, given local resistance patterns. We compared patient characteristics, appropriate ABC PPX use (deemed by local ABC Stewardship Team) and postoperative infections between the “pre” (01/01/2019 – 03/31/2019) and “post” (05/01/2019 – 07/31/2019) groups. Results The “pre” group had 85 patients and the “post” group had 80 patients. 62% had a same day UGY procedure with the most common procedures designated as “clean-contaminated” (81.8%) and ASA physical status classification as “ASA II” (53.9%). After the intervention, appropriate ABC PPX choice improved (14.5% to 76%, P < 0.001) based on local ABC resistance patterns. No significant difference is noted in urine culture collection before procedure (36.4% to 43.7%, P = 0.3), ABC PPX choice based on prior patient-specific culture results including multi-drug resistant pathogens (75% to 82.3%, P = 0.6), use of ABC PPX post-procedure (40% to 35%, P = 0.5) and postoperative infections (7% to 11.2%, P = 0.4). Conclusion Utilization of education sessions as a quality improvement intervention resulted in significant improvement in ABC PPX choice for UGY procedures based on local ABC resistance patterns. Further interventions are necessary to optimize additional areas related to ABC PPX use for UGY procedures. Disclosures All Authors: No reported disclosures

In the present study, we investigated the effects of dipeptides on melanogenesis in B16 melanoma cells. It was found that WV (Trp+Val), WM (Trp+Met), and CQ (Cys+Gln) decreased melanin production dosedependently. However, dipeptides did not directly inhibit tyrosinase activity, the rate-limiting melanogenic enzyme. Therefore, we further investigated the expression of tyrosinase. Our results showed that -MSH-induced tyrosinase expression was down-regulated by WV, WM, and CQ. Thus, we propose that WV, WM, and CQ show hypopigmentary activity through tyrosinase down-regulation.

Object Recent studies have emphasized measuring the sagittal vertical axis (SVA) and pelvic parameters (pelvic incidence, sacral slope, and pelvic tilt) when evaluating spinal disorders. An accurate and reproducible measurement is important for a reliable result. Although computerized measurement is more consistent than manual measurement, computerized measurement requires an expensive software program, the need to transfer images to a workstation, and additional education for users. An inexpensive and convenient computerized measurement program is desirable and necessary. The object of this study was to propose a computerized tool for measuring spinal and pelvic parameters and to evaluate the efficacy of this new tool compared with manual measurement. Methods The authors devised a tool that provides computerized measurements of the SVA and pelvic parameters in a picture archiving and communication system (PACS) without transferring images to another program. This tool was created by merging functions in the PACS. The resulting tool is easy to implement by merging functions (indicate the center of 2 points, plot a vertical and a horizontal line from a point, and measure the angles between lines) in any image viewer. The tool was made into icons on a toolbar in the PACS. Measurements of distance and angle were computerized by identifying crucial points after selecting the icon. For SVA, 4 points were identified around each corner of the C-7 body and a fifth point at the superior/posterior corner of the S-1 body. For pelvic parameters, 4 points were identified at the centers of each femoral head and at the anterior/superior and posterior/superior corners of S-1. Thirty-three whole-spine lateral radiographs were randomly selected from the radiographic database. To evaluate inter- and intraobserver variability between observers and method, skilled (2 years of experience) and unskilled (1 week of experience) observers measured SVA and pelvic parameters 3 times with a 7-day interval between each time using both computerized and manual measurement methods. The reliability was measured using the intraclass correlation coefficient. Results The computerized method showed better congruity than the manual method in both skilled and unskilled observers (p < 0.05), and the intraclass correlation coefficients were > 0.9. The skilled observer showed better agreement than the unskilled observer with both computerized and manual methods, and this difference was prominent in measuring pelvic parameters (p < 0.05). The computerized method required less time than the manual method, especially for the unskilled observer (p < 0.05). Conclusions A computerized measurement of pelvic parameters may be a more reliable and efficacious approach than manual measurements. This benefit is more prominent in the unskilled observer, and adding this simple function to an image viewer may be recommended in future studies.

E-cadherin (ECAD), a transmembrane glycoprotein that mediates adherens junctions, is developmentally restricted to polarized epithelial cells.1,2 Repeated extracellular domains of ECAD are responsible for binding cells to neighboring ones and maintaining the structural integrity and polarization of epithelia. ECAD also regulates signaling pathways through the intracellular catenin (ctn) binding domains.1,2 Cadherin switching is a characteristic behavior of the process of epithelial-mesenchymal transition (EMT). An important phenotypic change in cadherin switching is the loss of ECAD expression. The loss of ECAD causes cells to dissociate from their neighbors and results in a loss of cell polarity. This, in turn, leads to the activation of cell signaling pathways that regulate the mesenchymal transition. On the contrary, an increase in ECAD expression inhibits cell transformation and tumor cell invasion in an adhesion-independent manner.3,4 Myofibroblasts play a key role in wound healing and pathological organ remodeling.5 The most accepted myofibroblast progenitors in the liver are hepatic stellate cells (HSCs),5,6 although various other resident cells are recognized as sources of liver myofibroblasts.5 As HSCs activate, the level of ECAD expression decreases.7 Activated HSCs then promote the synthesis and deposition of the extracellular matrix (ECM) component and the induction of α-smooth muscle actin (αSMA). In addition, multiple signaling cascades accelerate the growth of activated HSCs6 and contribute to the development of liver fibrosis. Although the link between cadherin switching and the EMT process in HSCs has been studied,7,8 it is yet unclear whether ECAD affects the activation of HSCs. Moreover, the potential signaling and molecular regulatory mechanism by which ECAD antagonizes profibrogenic gene expression in quiescent HSCs has not been explored. Several lines of evidence indicate that transforming growth factor β1 (TGFβ1) from autocrine or paracrine sources plays a role in activating HSCs and increasing the synthesis of ECM proteins and cellular receptors for various matrix proteins.6 TGFβ1 is regulated transcriptionally by transcription factors and posttranslationally by the maturation of the precursors.6 In response to TGFβ1, type I and II TGFβ1 receptors form a complex and induce receptor autophosphorylation. TGFβ1 is also known as a cytokine that induces EMT, which inhibits ECAD expression by up-regulating transcriptional repressors such as Snail, Zeb, and Twist.9 Activated TGFβ1 receptors transmit the signal by which regulatory Smad molecules (Smad3/2) are phosphorylated and form an active complex with co-Smad (Smad4). The transcription factor complex then moves to the nucleus, in which it promotes the transcription of target genes through interactions with specific Smad binding elements (SBEs; also called the CAGA box).10 It has been reported that single or multiple copies of SBEs are located in the upstream regions of TGFβ1’s target genes, such as plasminogen activator inhibitor 1 (PAI-1), matrix metalloproteinases (MMPs), and collagen type I.11,12 Despite the finding that TGFβ1 leads to HSC activation with a phenotypic change of ECAD loss and causes hepatic ECM accumulation, it has not yet been determined whether ECAD overexpression inhibits the expression of TGFβ1 and its downstream target genes. We investigated whether ECAD negatively regulates TGFβ1 expression; we also examined what the molecular basis could be. Our findings demonstrate transcriptional repression of the TGFβ1 gene by ECAD. Thus, the loss of ECAD initiates TGFβ1 induction and consequently promotes the expression of genes for ECM accumulation. Moreover, the results of this study led to the identification of the p120-ctn binding domain of ECAD as the site required for complex formation with p120-ctn, which recruits ras homolog gene family A (RhoA); this results in the inhibition of RhoA activity. The data presented here support the ability of ECAD to hinder RhoA activity, which is critical for the Smad signaling pathway.

Ion doping effect on low temperature poly-Si films has been investigated to suggest CW laser dopant activation as an alternative to conventional thermal annealing. The poly-Si films were ion doped with various B2H6/H2 or PH3/H2 plasma ion doses at an acceleration voltage of 16 kV, a RF of 13.56 MHz, and a RF power of 20 W. Then, the dopant activation was carried out by laser scan or conventional thermal annealing. The properties of ion doped poly-Si were examined by sheet resistance measurement and Raman spectroscopy. The sheet resistance of the ion doped poly-Si after laser dopant activation is sufficiently low compared to the value measured after the thermal annealing. EBSD was also examined to clarify grain boundary condition.

We have developed a super large grain poly-Si on glass by CW laser crystallization using cylindrical microlens array. A giant-grain poly-Si with average grain size of 15 μm × 15 μm was achieved. The n-channel TFT using the poly-Si exhibited the field-effect mobility, on/off current ratio, threshold voltage and gate voltage swing of 470 cm2/Vs, ∼108, 0.1 V and 0.4 V/dec., respectively. On the other hand, the p-channel TFT exhibited 192 cm2/Vs, ∼108, −2.2 V and 0.5 V/dec., respectively. A single crystalline Si on glass can be achieved with this technique.

We report the formation of (001)-textured gains in (111) polycrystalline silicon (poly-Si) by Ni-mediated crystallization of amorphous silicon (a-Si) using a cap layer (MICC). The a-Si precursor deposited by plasma enhanced chemical vapor deposition was dehydrogenated at 550 °C and then crystallized at 580 °C. The (001)-textured grains appear in the network of (111) poly-Si of ∼ 100 μm grains, which was confirmed by the analysis of electron back-scattered diffraction. From the kinetic study of the grain growth, it is found that the nucleation rate of (001) nuclei is higher than that of (111) ones, but the (111) grains grow faster than that of (001) grains.

We report the preliminary results of the micro-structural change, especially crystalline grain size, on the effect of process parameters, such as amorphous silicon (a-Si) thickness and the width of Si island, via CW laser crystallization (CLC) of island-patterned a-Si thin films. We have found that the average grain boundary spacing, representing grain size, strongly depends on both the thickness and the width of the Si island. The grain size increases with increasing the film thickness in proportion until it reaches a certain value, and then saturates even though the thickness is further increased when the laser energy intensity is enough for inducing complete melting of the region. The grain size of the wider width of Si island is proved to be larger than that of the smaller width of Si island under given CLC conditions. This is thought to be due to the efficient energy absorption of the wider width of Si island. By optimization of process parameters, very high quality thick poly-Si film is demonstrated.

A simple and effective method for selective CW laser crystallization of a-Si (CLC) without pre-patterning of a-Si has been reported. By using a metallic shadow mask instead of a photolithographic process, we can reduce the process steps and time compared with a conventional CLC process. It shows very high performance – mobility of 173 cm2/s, Ioff of ∼10−13 A @ Vd = −5 V, Ion/Ioff of >108 – as a p-channel poly-Si TFT even without any pre-/post-treatment to improve TFT characteristics such as plasma hydrogenation.

We have studied the effect of Au addition on Ni-mediated crystallization of amorphous silicon(a-Si) using a silicon–nitride (SiNx) cap layer. The Ni and Au particles were sputtered on the SiNx∕a-Si and then the samples were heated for crystallization at a temperature of 550 °C. We achieved disk-shaped grains and found that the grain size increased with increasing Au density when the Ni density was fixed at 2.45×1014∕cm2. We achieved a grain size of ∼45μm, however the a-Si could not be crystallized when Au density is higher than Ni density.

Disk- and needle-shaped grains can be seen in polycrystalline silicon (poly-Si) made by Ni-mediated crystallization of amorphous silicon (a-Si). A major parameter to give the difference of grain structure is the Ni area density on a-Si. However, there are many other parameters such as heating rate and structure of a-Si to affect the grain structure. The use of Ni density of ∼1013cm−2 on a-Si for the crystallization gives the disk-shaped grains. There is no amorphous phase in the disk-shaped grains which are composed of well-aligned needles. On the other hand, the poly-Si has some amorphous phase inside when it was crystallized into needlelike rods. It is found that the width of needles in the disk-shaped grains is smaller than that of needlelike crystallites. The Ni atoms are at the grain boundaries formed by the collisions of neighboring grains.

Menadione is a synthetic vitamin K3 derivative. Here, we examined the effects of menadione on melanogenesis and its related signaling pathways. Our results showed that melanin content was significantly reduced after menadione treatment in a dose-dependent manner. However, menadione treatment did not reduce tyrosinase activity directly. Wnt signaling is known to play a major role in the control of melanin synthesis. Thus, we tested the effects of menadione treatment on GSK3β and β-catenin signaling, but found that menadione did not influence either of these signaling pathways. We also investigated changes in the phosphorylation of ERK, which is related to melanin regulation. These results indicated that menadione treatment led to the phosphorylation of ERK. Additionally, menadione treatment reduced both MITF and tyrosinase protein levels. Treatment with PD98059, a specific ERK pathway inhibitor, restored menadione-induced melanin reduction and also prevented MITF and tyrosinase downregulation by menadione. These results suggest that the hypopigmentary action of menadione is due to MITF and tyrosinase downregulation by ERK activation.

Aims Geranylgeranylacetone (GGA) has shown cytoprotective activity through induction of a 70-kDa heat shock protein (HSP70). Although HSP70 is reported to regulate melanogenesis, the effects of GGA on melanin synthesis in melanocytes have not been previously studied. Therefore, this study investigated the effects of GGA on melanogenesis and the related signaling pathways. Main methods Melanin content and tyrosinase activities were measured in Mel-Ab cells. GGA-induced signal transduction pathways were investigated by western blot analysis. Key findings Our results showed that GGA significantly decreased melanin content in a concentration-dependent manner. Similarly, GGA reduced tyrosinase activity dose-dependently, but it did not directly inhibit tyrosinase. Western blot analysis indicated that GGA downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase protein expression, whereas it increased the phosphorylation of extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Furthermore, a specific ERK pathway inhibitor, PD98059, blocked GGA-induced melanin reduction and then prevented downregulation of MITF and tyrosinase by GGA. However, a specific mTOR inhibitor, rapamycin, only slightly restored inhibition of melanin production by GGA, indicating that mTOR signaling is not a key mechanism regulating the inhibition of melanin production. Significance These findings suggest that activation of ERK by GGA reduces melanin synthesis in Mel-Ab cells through downregulation of MITF and tyrosinase expression.

Langer–Giedion syndrome (LGS; MIM 150230 ), also called trichorhinophalangeal syndrome type II (TRPS2), is a contiguous gene syndrome caused by a one-copy deletion in the chromosome 8q23-q24 region, spanning the genes TRPS1 and EXT1. We identified an LGS family with two affected and two unaffected siblings from unaffected parents. To investigate the etiology of recurrence of LGS in this family, array CGH was performed on all family members. We identified a 7.29 Mb interstitial deletion at chromosome region 8q23-q24 in the two affected siblings, but no such deletion in the unaffected family members. However, the mother and one of the two unaffected siblings carried a 1.29 Mb deletion at chromosome region 8q24.1, sharing the distal breakpoint with the larger deleted segment found in the affected siblings. Another unaffected sibling had a 6.0 Mb duplication, sharing the proximal breakpoint of the deletion in the affected siblings. Karyotypic and FISH analyses in the unaffected mother revealed an insertional translocation of 8q23-q24 genomic material into chromosome 13: 46,XX,ins(13;8)(q33;q23q24). This insertional translocation in the mother results in the recurrence of LGS in this family, highlighting the importance of submicroscopic rearrangements in the genetic counseling for LGS.

Deferoxamine (DFX), a potent iron-chelating agent, reduces brain edema and neuronal cell injury that develop due to the hemolysis cascade. Statins have neuroprotective effects via anti-inflammatory action and increment of cerebral blood flow after intracerebral hemorrhage (ICH). The purpose of this study was to identify the effects of combined DFX and statins treatment in an experimental ICH rat model. The treatments were: intraperitoneal (i.p.) injection of DFX (group I), combined treatment of i.p. DFX and oral statins (group II), statins only (group III) and treatment with vehicle (group IV). Induction of ICH was performed with injection of bacterial collagenase type IV into the left striatum. After removal of the brain, hematoma volume, water content and brain atrophy were measured. Immunohistochemistry in the perihematomal region was performed for identification of microglial infiltration, astrocyte expression and apoptotic cell presence. Statistical analysis was performed using the non-parametric Kruskal-Wallis test and significance was evaluated when the p value was less than 0.05. According to behavioral tests, significant differences among treatment groups were noted 4 weeks after ICH induction (p < 0.05). However, there were no significant differences among treatment groups in hematoma volume, brain water content or brain atrophy. In the perihematomal area, the activated microglial cells were reduced in the combined treatment group. Among the four groups, a significant difference in immunohistochemical staining was identified (p < 0.05). These results suggest that combined treatment with DFX and statins improves neurologic outcomes after ICH through reduction of microglial infiltration, apoptosis, inflammation and brain edema.

Objective The purpose of the present study is to assess the possibility of disc regeneration by treatment with adipose-derived stem cells (ADSCs) in a rabbit model of degenerative disc disease, and to evaluate the efficacy of a percutaneous technique for constructing a model of degenerative disc disease in rabbits. Methods The study sample consisted of 20 mature male New Zealand white rabbits. Intervertebral discs were injured in each rabbit by a percutaneous technique at L2-3, L3-4, and L4-5 under C-arm guidance with a 19-gauge spinal needle. Magnetic resonance images (MRI) were checked at 6, 9, 12, and 15 weeks after injury to evaluate disc degeneration. Nineteen weeks after injury, ADSCs were injected into the L4-5 disc space, with saline injected into the L3-4 disc as a control, using a 21-gauge spinal needle. Histologic confirmations of degenerated discs were performed at 10 and 18 weeks after injury with safranin O and trichrome stains. Results MRI revealed intervertebral disc degeneration from 9 weeks after injury, and full degeneration at 15 weeks after injury, when compared with uninjured control discs. We confirmed the proliferation of ADSCs at the L4-5 level in 10-week rabbits after cell injection. Histologically, the ADSC-injected discs exhibited elevated extracellular matrix secretion and little ossification of damaged cartilage in the nucleus pulposus compared with degenerative control discs. Conclusions These results suggest that the injection of ADSCs into injured lumbar discs could be an effective treatment for degenerative disc disease by promoting the cartilage regeneration.

Corticotropin-releasing factor (CRF) is a peptide involved in the activation of the hypothalamic-pituitary-adrenal (HPA) axis. CRF is distributed not only along the HPA axis but also throughout pain-relevant anatomical sites. CRF elicits potent antinociception at the three main levels of pain transmissions: namely, the brain, spinal cord, and peripheral sensory neurons. The widespread distribution of CRF receptors 1 and 2 in the brain offers several targets wherein CRF could alter pain, some of which may be independent of the HPA axis. In this study, we assessed the expression of CRF and its receptors, CRF receptor type (CRFR)1 and CRFR2, in the spinal dorsal horn and dorsal root ganglion (DRG) in a rat model of neuropathic pain induced by spinal nerve injury (SNI). CRF was expressed in a few DRG neurons and primary afferent fibers in the dorsal horns of naїve rats, and the CRF-positive neurons in DRG and fibers in the spinal dorsal horn were found to have increased after SNI. CRFR1 was not expressed in DRG or the dorsal horn and CRFR2 was expressed weakly in the small neurons in DRG in the naїve rats. After SNI, CRFR1 was expressed in the activated microglia in the ipsilateral dorsal horn, and immunoreaction for CRFR2 was increased in the contralateral DRG following SNI. Consequently, it has been suggested that the increased expression of CRF and CRFR2 in DRG neurons and primary afferent fibers in dorsal horn, and CRFR1 in the activated microglia, may be involved in the mediation of stress responses as well as in microglial activation in the neuropathic pain state following SNI.

OBJECTIVE: Transient receptor potential vanilloid subfamily type 1 (TRPV1), a most specific marker of the nociceptive primary afferent, is expressed in peptidergic and non-pepetidergic primary afferents innervating skin and viscera. However, its expression in sensory fibers to skeletal muscle is not well known. In this study, we studied the neurochemical characteristics of TRPV1-positive primary afferents to skeletal muscles. METHODS: Sprague-Dawley rats were injected with total 20 microl of 1% fast blue (FB) into the gastrocnemius and erector spinae muscle and animals were perfused 4 days after injection. FB-positive cells were traced in the L4-L5 (for gastrocnemius muscle) and L2-L4 (for erector spinae muscle) dorsal root ganglia. The neurochemical characteristics of the muscle afferents were studied with multiple immunofluorescence with TRPV1, calcitonin gene-related peptide (CGRP) and P2X(3). To identify spinal neurons responding to noxious stimulus to the skeletal muscle, 10% acetic acids were injected into the gastrocnemius and erector spinae muscles and expression of phospho extracellular signal-regulated kinase (pERK) in spinal cords were identified with immunohistochemical method. RESULTS: TRPV1 was expressed in about 49% of muscle afferents traced from gastrocnemius and 40% of erector spinae. Sixty-five to 60% of TRPV1-positive muscles afferents also expressed CGRP. In contrast, expression of P2X(3) immnoreaction in TRPV1-positive muscle afferents were about 20%. TRPV1-positive primary afferents were contacted with spinal neurons expressing pERK after injection of acetic acid into the muscles. CONCLUSION: It is consequently suggested that nociception from skeletal muscles are mediated by TRPV1-positive primary afferents and majority of them are also peptidergic.

In this study, we isolated scopoletin from Cirsium setidens Nakai (Compositae) and tested its effects on melanogenesis. Scopoletin was not toxic to cells at concentrations less than 50 µM and increased melanin synthesis in a dose-dependent manner. As melanin synthesis increased, scopoletin stimulated the total tyrosinase activity, the rate-limiting enzyme of melanogenesis. In a cell-free system, however, scopoletin did not increase tyrosinase activity, indicating that scopoletin is not a direct activator of tyrosinase. Furthermore, Western blot analysis showed that scopoletin stimulated the production of microphthalmia-associated transcription factor (MITF) and tyrosinase expression via cAMP response element-binding protein (CREB) phosphorylation in a dose-dependent manner. Based on these results, preclinical and clinical studies are needed to assess the use of scopoletin for the treatment of vitiligo.

Background & Aims Hepatocyte injury occurs during liver fibrogenesis. MicroRNAs (miRNA) regulate some of these processes, and some are regulated by the farnesoid X receptor (FXR). We investigated the effect of repression of specific miRNAs by FXR in hepatocyte injury using fibrotic liver tissue from patients and hepatocytes. Methods We used immunohistochemistry or real-time polymerase chain reaction to analyze proteins and miRNAs in human and mouse liver samples. HepG2 cells were transfected with pre-miRNA, antisense oligonucleotides, small interfering RNAs, the 3′-untranslated region of liver kinase B1 (LKB1) (STK11), or constructs for overexpression, and analyzed. Results Liver tissue from patients with severe fibrosis had lower levels of FXR and greater amounts of hepatocyte death than samples from patients with mild disease. Levels of several miRNAs changed when FXR expression was disrupted in the liver; one of these, miR-199a-3p, was significantly up-regulated in patients with severe fibrosis. Activation of FXR by its ligand reduced the level of miR-199a-3p in HepG2 cells. LKB1 messenger RNA was identified as a target of miR-199a-3p, and its expression was reduced in human fibrotic liver tissue. Overexpression of FXR or incubation of cultured hepatocytes with the FXR ligand up-regulated LKB1; LKB1 was not induced in cells transfected with miR-199a-3p. Incubation of HepG2 cells with FXR ligand, or injection of the ligand into mice, protected hepatocytes from injury and increased levels of LKB1; levels of miR-199a-3p were reduced compared with cells that were not incubated with the FXR ligand. Activation of FXR reduced mitochondrial dysfunction and oxidative stress and increased hepatocyte survival. Conclusions In hepatocytes, FXR represses production of miR-199a-3p. In fibrotic livers of humans and mice, FXR expression is reduced, increasing levels of miR-199a-3p, which reduces levels of LKB1. FXR therefore protects hepatocytes from injury by repressing miR-199a-3p and thereby increasing levels of LKB1.

This study investigated the effects of proline-serine (PS) and valine-serine (VS) dipeptides on melanogenesis in Mel-Ab cells. Proline-serine and VS significantly inhibited melanin synthesis in a concentration-dependent manner, though neither dipeptide directly inhibited tyrosinase activity in a cell-free system. Both PS and VS down-regulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. In a follow-up study also described here, the effects of these dipeptides on melanogenesis-related signal transduction were quantified. Specifically, PS and VS induced ERK phosphorylation, though they had no effect on phosphorylation of the cAMP response element binding protein (CREB). These data suggest that PS and VS inhibit melanogenesis through ERK phosphorylation and subsequent down-regulation of MITF and tyrosinase. Properties of these dipeptides are compatible with application as skin-whitening agents.

We investigated the threshold voltage (Vth) instability for various gate dielectrics (SiNx and SiOx) in amorphous indium-gallium-zinc oxide (a-IGZO) thin film transistors (TFTs). The a-IGZO TFTs with SiNx 150 °C exhibited reasonable electrical performance (field-effect mobility of 8.1 cm2/V s and Ion/off ratio of >108) but showed huge Vth shift under positive gate bias. The TFTs with SiOx dielectrics exhibit smaller Vth instability than those of SiNx dielectrics. This behavior can be explained by using simple charge trapping into the gate insulators and the difference of Vth instability on various dielectrics may be originated from the hydrogen contents, providing high density of charge traps in gate dielectrics.

The electrical instability in thin-film transistors (TFTs) based on amorphous indium-gallium-zinc oxide (a-IGZO) was investigated using constant bias and constant current stress. Stress conditions were chosen such that TFT is turned on, whereas the potential at the gate dielectric-a-IGZO interface is below the electron accumulation threshold. Drain current in this low bias regime is still sufficient for driving pixels in an organic light-emitting diode display (AMOLED). We found that the degradation is due to charge trapping near the a-IGZO-gate dielectric interface. The obtained results enabled a straightforward assessment of a-IGZO TFTs' instability for their application in AMOLEDs.

We studied the Ni-mediated crystallization of amorphous silicon (a-Si) as a function of its thickness. It was found that the orientation of the poly-Si changed from [110] to [001] when its thickness reduced down to 16 nm.This was confirmed by the analysis of electron backscattered diffraction pattern. The growth of (100)-oriented poly-Si is due to the predominant formation of [001] NiSi 2 nuclei in a thin a-Si network because of its smaller crystalline size compared to that of [110] nuclei.

We studied the metal-induced crystallization of a-Si using a Ni-ferritin molecule of 7 nm diameter. The Ni-ferritin molecules were coated onto the SiN x /amorphous silicon (a-Si)/buffer/glass and it was heated at 580°C for 20 h for crystallization after UV burning of the biomaterial. It was found that the grain size of poly-Si increases with decreasing the ferritin density. A grain size of ∼220 μm was achieved, and its surface roughness was 2.1 nm.

We studied the location control of a giant grain of polycrystalline silicon produced by Ni-mediated crystallization of amorphous silicon (a-Si) using a cap layer. An organic lens made of acryl was used for the focusing of light for the seed formation and subsequent crystallization. A single grain 62μm in diameter was made using an 80-μm-square SiNx cap layer on the a-Si. The position of a thin-film transistor (TFT) on a grain can be controlled, so that a single grain TFT can be fabricated at a predetermined position without use of the laser annealing technique.

We developed a 2.0 inch, QCIF (160×128×RGB), a-Si:H TFT-LCD with a low noise gate driver integrated on glass substrate. By simulation and measurement, the proposed gate driver was found to be noise-free compared to conventional one. A new gate driver can make it possible to perform operation regardless of the voltage coupling from other voltage sources.