BackgroundEstablished measurements of proliferation in breast cancer are Ki67 and mitotic-activity-index (MAI), with problems in reproducibility and prognostic accuracy. Phosphohistone H3 (PHH3), a relatively novel IHC marker is specific for mitosis with good reproducibility. We hypothesized that PHH3 would be more reproducible and better represent proliferation than Ki67.ResultsPHH3 identified easily-missed mitosis by MAI, as demonstrated by upgrading M grade at diagnosis (n = 29/218, evenly distributed). PHH3 accurately found hot-spots, supported by mitotic count agreement between low-power and 10HPFs (R2 = 0.999; P = 0.001). PHH3 was more reproducible than Ki67, measured by five-rater inter-class correlation coefficient (0.904 > 0.712; P = 0.008). Finally, despite a relatively short follow-up (median 46 months; 7 recurrences) PHH3 was the only variable correlated with disease-free survival (P = 0.043), while all other conventional clinicopathologic variables, including Ki67 (P = 0.356), did not.Materials and MethodsWe compared Ki67 and PHH3 for 218 breast cancer surgical cases diagnosed from 2012 to 2013 at Severance hospital. The most representative invasive breast cancer surgical slides were immunohistochemically stained for Ki67 and PHH3.ConclusionsPoor reproducibility and inadequate representation of proliferation of Ki67 and MAI may be improved by PHH3, allowing better accuracy in breast cancer diagnostics.
Two-dimensional (2-D) metal chalcogenides have received great attention because of their unique properties, which are different from bulk materials. A challenge in implementing 2-D metal chalcogenides in emerging devices is to prepare a well-crystallized layer over large areas at temperatures compatible with current fabrication processes. Tin monosulfide, a p-type layered semiconductor with a high hole mobility, is a promising candidate for realizing large-area growth at low temperatures because of its low melting point. However, tin sulfides exist in two notable crystalline phases, SnS and SnS2. Therefore, it is imperative to control the oxidation state of Sn to achieve a pure SnS film. Here, the synthesis of SnS thin films by atomic-layer-deposition (ALD) is demonstrated using bis(1-dimethylamino-2-methyl-2-propoxy)tin(II) and H2S as Sn and S sources, respectively, over a wide temperature window (90–240 °C). Impurities such as carbon, oxygen, and nitrogen were negligibly detected. The morphological evolution of plate-like orthorhombic SnS grains was observed above 210 °C. Moreover, properties of thin film transistors and gas sensors using SnS films as the active layers were investigated. The SnS ALD process would provide promising opportunities to exploit the intriguing properties of the 2-D metal chalcogenides for realizing emerging electronic devices.
Ni thin films were deposited by atomic layer deposition ͑ALD͒ using bis͑dimethylamino-2-methyl-2-butoxo͒nickel ͓Ni͑dmamb͒ 2 ͔ as a precursor and NH 3 gas as a reactant. The growth characteristics and film properties of ALD Ni were investigated. Lowresistivity films were deposited on Si and SiO 2 substrates, producing high-purity Ni films with a small amount of oxygen and negligible amounts of nitrogen and carbon. Additionally, ALD Ni showed excellent conformality in nanoscale via holes. Utilizing this conformality, Ni/Si core/shell nanowires with uniform diameters were fabricated. By combining ALD Ni with octadecyltrichlorosilane ͑OTS͒ self-assembled monolayer as a blocking layer, area-selective ALD was conducted for selective deposition of Ni films. When performed on the prepatterned OTS substrate, the Ni films were selectively coated only on OTS-free regions, building up Ni line patterns with 3 m width. Electrical measurement results showed that all of the Ni lines were electrically isolated, also indicating the selective Ni deposition.As scaling continues in order to improve device integration in the complementary metal-oxide-semiconductor ͑CMOS͒ process, the silicidation process becomes more essential for lowering contact resistance and increasing drive currents. 1 TiSi 2 and CoSi 2 have been extensively investigated as contact materials. However, these materials have been reported to cause increased series resistance of devices at the sub-65 nm technology node. 2 In addition, TiSi 2 exhibits the narrow line effect. 3 Although CoSi 2 lines depend less on the sheet resistance, the greater consumption of Si is a major concern in forming silicide with the decreased junction depth. Also, both materials require a two-step annealing process to form a low resistive phase. 3 Because of these problems, NiSi is being investigated as a contact material for application in nanoscale devices and shows no linewidth effects, low resistivity, low Si consumption, low process temperature, and a one-step annealing process. 4 The Ni metal deposition process is a key requirement in the formation of Ni silicide contacts. Among the various thin film deposition techniques, atomic layer deposition ͑ALD͒ is a promising method which exhibits good conformality and uniformity, atomic scale thickness controllability, and low impurity contamination at a low growth temperature due to its growth mechanism based on a self-limited surface reaction. 5-7 However, in spite of its importance in nanoscale device contact applications, there are only a few reports on the ALD of Ni films. 2,[8][9][10][11][12][13] In an early study, Chae et al. reported the formation of Ni films by H 2 plasma reduction of ALD NiO films using bis͑cyclopentadienyl͒nickel ͓NiCp 2 ͔ as a precursor and water as a reactant. 9 Later, Do et al. reported a Ni ALD process using a Ni͑dmamb͒ 2 precursor and H 2 as the reactant gas. 2 However, the Ni films deposited in these studies contain a large amount of carbon, which may have caused high resistivity. 2,9 These results suggest t...
Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous entity
Low-temperature growth of InO films was demonstrated at 70-250 °C by plasma-enhanced atomic layer deposition (PEALD) using a newly synthesized liquid indium precursor, dimethyl(N-ethoxy-2,2-dimethylcarboxylicpropanamide)indium (MeIn(EDPA)), and O plasma for application to high-mobility thin film transistors. Self-limiting InO PEALD growth was observed with a saturated growth rate of approximately 0.053 nm/cycle in an ALD temperature window of 90-180 °C. As-deposited InO films showed negligible residual impurity, film densities as high as 6.64-7.16 g/cm, smooth surface morphology with a root-mean-square (RMS) roughness of approximately 0.2 nm, and semiconducting level carrier concentrations of 10-10 cm. Ultrathin InO channel-based thin film transistors (TFTs) were fabricated in a coplanar bottom gate structure, and their electrical performances were evaluated. Because of the excellent quality of InO films, superior electronic switching performances were achieved with high field effect mobilities of 28-30 and 16-19 cm/V·s in the linear and saturation regimes, respectively. Furthermore, the fabricated TFTs showed excellent gate control characteristics in terms of subthreshold swing, hysteresis, and on/off current ratio. The low-temperature PEALD process for high-quality InO films using the developed novel In precursor can be widely used in a variety of applications such as microelectronics, displays, energy devices, and sensors, especially at temperatures compatible with organic substrates.
Background: Intrahepatic cholangiocarcinoma (iCCA) is subclassified into mass-forming (MF), periductal-infiltrative (PI), and mixed types grossly; however, their clinicopathological significance remains controversial.Methods: Clinicopathological characteristics of iCCA gross types were analysed according to histopathological type (small-duct, large-duct, indeterminate) or cholangiolocellular differentiation trait (CDT) in 108 iCCAs. The expression levels of inflammation-marker (CRP, FGB) and proliferation-marker (phospho-ERK1/2, Ki-67) were evaluated by immunohistochemistry.Results: There were 87 MF, 8 PI, and 13 mixed-gross type. Small-duct-type (39, 44.8%) and CDT (19, 21.8%) were found only in MF-gross type. The inflammation-marker expression was higher in MF-type than in PI-and mixed-gross types (P = 0.023). It was high in small-duct-type, middle in indeterminatetype, and low in large-duct-type (P = 0.015), and iCCAs with CDT showed higher inflammation-marker expression compared to those without (P < 0.001). Proliferation-marker expression did not differ according to gross type; however it was lower in iCCA with CDT compared to those without (P = 0.004). Subgrouping of the gross type according to histopathological type or CDT revealed that MF-type with small-duct-type or CDT had better overall survival compared to the others (P < 0.05). Conclusion:MF-type iCCA is more heterogeneous than other gross types. High inflammation-marker/ low proliferation-marker expression in MF-type with CDT or small-duct-type may be related to a good outcome.
Research on two-dimensional (2D) metal dichalcogenides is rapidly expanding owing to their unique characteristics that do not exist in bulk materials. The industrially compatible development of these emerging materials is indispensable to facilitate the transition of 2D metal dichalcogenides from the research stage to the practical industrial application stage. However, an industrially relevant method, i.e., the low-temperature synthesis of wafer-scale, continuous, and orientation-controlled 2D metal dichalcogenides, still remains a significant challenge. Here, we report the low-temperature (≤350 °C) synthesis of uniform and continuous n-type SnS2 thin films via the combination of atomic layer deposition (ALD) of tin oxides and subsequent sulfurization. Well-crystallized and aligned SnS2 layers parallel to the substrate are demonstrated through the phase engineering of the ALD-grown tin oxide and the substrate surface. The additional H2S plasma treatment at 300 °C leads to the formation of stoichiometric SnS2. The formation of conformal SnS2 layers over a three-dimensional undulating hole structure is confirmed, which reveals the potential for applications beyond the planar structured architecture. The present results could be a step toward the realization of 2D metal dichalcogenides in industry.
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