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Solution-processed oxide thin films have many attractive features for various electronic applications as like a next generation display and flexible electronics. But a high temperature annealing is often required to obtain high quality oxide thin film and the applications of solution-processed thin films are limited. To overcome this limit, we adopted a strategy that utilizes chemical driving force in addition to thermal energy. We chose precursors that can react each other and condensate via non-hydrolytic ester elimination reaction. To prove our concept a zinc tin oxide thin film transistor was fabricated with thermal annealing at low-temperature down to 300 °C. Although the oxide film was processed with low-temperature annealing, fabricated thin film transistors were functional and mobility of those of devices exceeded 1.0 cm2 V−1 s−1.

Bone tissue engineering scaffolds offer the merits of minimal invasion as well as localized and controlled biomolecule release to targeted sites. In this study, we prepared injectable hydrogel systems based on visible light-cured glycol chitosan (GC) hydrogels containing bone morphogenetic protein-2 (BMP-2) and/or transforming growth factor-beta1 (TGF-&beta, 1) as scaffolds for bone formation in vitro and in vivo. The hydrogels were characterized by storage modulus, scanning electron microscopy (SEM) and swelling ratio analyses. The developed hydrogel systems showed controlled releases of growth factors in a sustained manner for 30 days. In vitro and in vivo studies revealed that growth factor-loaded GC hydrogels have no cytotoxicity against MC3T3-E1 osteoblast cell line, improved mRNA expressions of alkaline phosphatase (ALP), type I collagen (COL 1) and osteocalcin (OCN), and increased bone volume (BV) and bone mineral density (BMD) in tibia defect sites. Moreover, GC hydrogel containing BMP-2 (10 ng) and TGF-&beta, 1 (10 ng) (GC/BMP-2/TGF-&beta, 1-10 ng) showed greater bone formation abilities than that containing BMP-2 (5 ng) and TGF-&beta, 1 (5 ng) (GC/BMP-2/TGF-&beta, 1-5 ng) in vitro and in vivo. Consequently, the injectable GC/BMP-2/TGF-&beta, 1-10 ng hydrogel may have clinical potential for dental or orthopedic applications.

Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n=57), BRAF K601E (n=11), or RAS (n=64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.

Aim To investigate the relationship between mammographic breast density (MGD) and background parenchymal enhancement (BPE) at breast MRI and histopathological features of invasive breast cancers. Materials and methods A total of 178 women with unilateral invasive breast cancer who preoperatively underwent mammography and breast MRI were included in the study. Two radiologists rated MGD and BPE according to BI-RADS criteria in consensus. The relationship between MGD and BPE was investigated, and compared with histopathological features of invasive breast cancers according to the level of MGD and BPE. Results At MRI, there is no significant difference in the distribution of MGD and BPE of the contralateral breast in women with invasive breast cancer according to menopausal status (p=0.226, 0.384). Women with high MGD (>50% glandular) were more likely to have oestrogen-receptor (ER)-positive breast cancer (p=0.045) and progesterone receptor (PR)-positive breast cancer (p=0.020). With regard to BPE, PR positivity correlated with moderate or marked BPE with borderline significance (p=0.054). Multivariate logistic regression analyses revealed that women with high MGD were less likely to have triple-negative (i.e., a cancer that is ER negative, PR negative, and human epidermal growth factor receptor type 2 [HER2] negative) breast cancer compared with ER (+)/HER2 (−) cancer (OR=0.231, 95% CI: 0.070, 0.760; p=0.016). No association between the histological tumour characteristics and BPE was observed. Conclusion In women with invasive breast cancer, high MGD is associated with ER positivity of the invasive breast cancer. However, at MRI, BPE of the contralateral breast seems to be independent of tumour characteristics.

Purpose: The anticancer property and cytoprotective role of selenium in chemotherapy have been reported. However, the combination effects of selenium on chemotherapy for advanced breast cancer have not yet been clearly defined. The purpose of this study was to investigate the combined effects of selenium on chemotherapy using docetaxel on breast cancer cell lines. Methods: Under adherent culture conditions, two breast cancer cell lines, MDA-MB-231 and MCF-7, were treated with docetaxel at 500pM and selenium at 100nM, 1μM, or 10μM. Changes in cell growth, cell cycle duration, and degree of apoptosis after 72 hours in each treated group were evaluated. Results: In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10mM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group. Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells. However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group. Conclusion: Our in vitro study indicated that the combination of selenium with docetaxel inhibits cell proliferation through apoptosis and cell arrest in the G2/M phase in MDA-MB-231 breast cancer cells.

SummaryObjective RAS mutations are the most common mutations in thyroid nodules with indeterminate cytology by fine-needle aspiration cytology (FNAC), and are mutually exclusive with BRAF mutations. However, the diagnostic utility of RAS mutation analysis is uncertain. We evaluated the diagnostic utility of RAS mutation analysis in indeterminate thyroid nodules. Design, patients, and measurements A total of 155 thyroid nodules (90 benign and 65 indeterminate) negative for BRAFV600E mutations on FNAC were analysed for mutations in RAS codon 61 using pyrosequencing methods. We evaluated diagnostic accuracy of RAS mutation for predicting thyroid malignancy based on the surgical pathologic diagnosis. Results Among the 65 BRAFV600E-negative indeterminate thyroid nodules identified by FNAC, 25 (38·5%) exhibited point mutations in RAS 61 consisting of 18 NRAS 61 (72%), and 7 HRAS 61 (28%) mutations. In contrast, only five of 90 (5·6%) nodules with benign cytology had RAS mutations. Only two of 25 (8·0%) RAS 61+ indeterminate nodules exhibited malignant ultrasonographic features. Of the 15 patients with RAS 61+-indeterminate nodules who underwent thyroid surgery, 14 (93·3%) were diagnosed as malignant, including 13 follicular variant of papillary thyroid carcinomas (FVPTC), and one follicular thyroid carcinoma (FTC). The average tumour size was 1·79 ± 0·62 cm. Multifocality was seen in 28·6% of cases, with 7·1% exhibiting extrathyroidal extension; no lymph node or distant metastases were evident. Based on the surgical pathologic diagnosis results, preoperative RAS 61 mutation analysis on FNAC exhibited 93·3% sensitivity, 75·0% specificity, 93·3% positive predictive value, 75·0% negative predictive value and 89·5% diagnostic accuracy for predicting malignancies. Conclusion Our results suggest that RAS mutation analysis holds great promise as a preoperative diagnostic tool for predicting FVPTC in cytologically and sonographically indeterminate nodules negative for BRAF mutations.

The objective of the present study was to evaluate the clinical and imaging characteristics of T1-T2 breast cancer with nodal metastasis and compare these features of pN2 or higher disease against those of pN1 disease.The mammographic, ultrasonographic and magnetic resonance imaging MRI features of 163 patients with T1-T2 cancer and nodal metastasis were retrospectively reviewed by two radiologists in consensus and compared between pN1 and pN2, or higher disease. Their clinical features were also compared.T1-T2 cancer with pN2 or higher disease is more likely to present with pleomorphic or linear-branching calcifications (p=0.003) on mammography and have non-parallel orientation on ultrasonography (p=0.008). Invasive tumor size larger than 2 cm (p=0.032), high histological grade (p=0.002) and lymphovascular invasion (p=0.009) were significantly associated with pN2 or higher disease.Being familiar with the imaging characteristics of T1-T2 cancer with nodal metastasis may be helpful in preoperatively evaluating the extent of nodal disease.

We investigated whether the interpretation of breast-specific gamma imaging (BSGI) with visual and semiquantitative analyses can improve the diagnosis of breast cancer.The records of 114 women (mean age±SD, 49.6±9.8 years) who underwent BSGI, mammography, and ultrasound to evaluate a breast lesion or lesions were reviewed retrospectively. The breast lesions identified with BSGI were compared with those identified with mammography and ultrasound. BSGI was first interpreted visually, and then a semiquantitative analysis was performed. For the semiquantitative analysis, the uptake ratio for each breast lesion was calculated by dividing the tumor uptake by the contralateral normal breast uptake.Four of the 114 patients had two breast lesions, so a total of 118 breast lesions (42 malignant lesions and 76 benign lesions) were evaluated. A BSGI uptake ratio cutoff of 1.5, with values less than 1.5 indicating negative for cancer, as determined by receiver operating characteristic curve analysis of our data (area under curve, 0.874), was used for semi-quantitative analysis. The sensitivity and specificity of BSGI with visual analysis alone for assessing malignant breast lesions were 76.2% (32/42) and 81.6% (62/76), respectively. For BSGI with visual and semiquantitative analyses, the sensitivity and specificity were 76.2% (32/42) and 92.1% (70/76), respectively. The sensitivity and specificity for mammography were 57.1% (24/42) and 81.6% (62/76), respectively. For ultrasound, the respective values were 97.6% (41/42) and 61.8% (47/76). BSGI with visual and semiquantitative analyses had a significantly higher specificity than BSGI with visual analysis alone, mammography, and ultrasound (all, p0.01).Semiquantitative analysis of BSGI with visual interpretation may be a useful complementary method for evaluating malignant breast lesions.

Background Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration ClinicalTrials.gov Identifier NCT01589367

Deferoxamine (DFA, N′-[5-(acetyl-hydroxy-amino)- pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl) propanoylamino] pentyl]-N-hydroxy-butane diamide) is a chelating agent used to remove excess iron from the body and to reduce organ and tissue damage. DFA enhances both iron regulatory protein 1 (IRP1) expression and its endoplasmic reticulum (ER) membrane-binding activity, as occurs in hypoxia, an ER stress, in cultured cells. Here, we show that DFA promotes ER stress via an ER signal pathway

Human urinary bladder cancer is the fifth most common cancer, with a worldwide estimate of about two million patients. Recurrence after complete transurethral prostatic resection is the most important problem in therapy. Combination therapy is a new approach in the treatment of cancers that do not respond to current therapies. These therapies have many advantages over conventional therapies, such as fewer side-effects and greater efficiency. Research efforts using natural compounds for the elimination or growth suppression of the cancer arise from studies on methylsulfonylmethane (MSM). MSM is a natural sulfur compound with no side-effects. AG490 is a tyrosine kinase inhibitor that has been extensively used for inhibiting Jak2 in vitro and in vivo. In our study, the combinatorial effect of these two agents on human bladder cancer cell lines and xenografts was analyzed. We observed that the combination of AG490 and MSM inhibited cancer cell viability and cell migration in vitro. This combination inhibited VEGF mRNA expression in bladder cancer cell lines. In vivo experiments showed that oral administration of AG490 and MSM combination significantly inhibited the growth of tumor xenografts in mice. Our study clearly demonstrates that the predominant effect of this combination is the reduction of signaling molecules including STAT3, STAT5b, IGF-1R, VEGF and VEGF-R2 which are involved in the growth, progression and metastasis of human bladder cancer. The anti-metastatic ability of this drug combination is confirmed using metastatic animal models. Therefore, this combination could have the effect of genesistasis and powerful anticancer effects against bladder cancer.

Herein, we report a novel and easy strategy for fabricating solution-processed metal oxide thin-film transistors by controlling the dielectric constant of H2O through manipulation of the metal precursor solution temperature. As a result, indium zinc oxide (IZO) thin-film transistors (TFTs) fabricated from IZO solution at 4 °C can be operated after annealing at low temperatures (∼250 °C). In contrast, IZO TFTs fabricated from IZO solutions at 25 and 60 °C must be annealed at 275 and 300 °C, respectively. We also found that IZO TFTs fabricated from the IZO precursor solution at 4 °C had the highest mobility of 12.65 cm2/(V s), whereas the IZO TFTs fabricated from IZO precursor solutions at 25 and 60 °C had field-effect mobility of 5.39 and 4.51 cm2/(V s), respectively, after annealing at 350 °C. When the IZO precursor solution is at 4 °C, metal cations such as indium (In3+) and zinc ions (Zn2+) can be fully surrounded by H2O molecules, because of the higher dielectric constant of H2O at lower temperatures. These chemical complexes in the IZO precursor solution at 4 °C are advantageous for thermal hydrolysis and condensation reactions yielding a metal oxide lattice, because of their high potential energies. The IZO TFTs fabricated from the IZO precursor solution at 4 °C had the highest mobility because of the formation of many metal-oxygen-metal (M-O-M) bonds under these conditions. In these bonds, the ns-orbitals of the metal cations overlap each other and form electron conduction pathways. Thus, the formation of a high proportion of M-O-M bonds in the IZO thin films is advantageous for electron conduction, because oxide lattices allow electrons to travel easily through the IZO.

In this paper, solution-based deposition of HfO2 thin film at low temperature was demonstrated. By using aqueous HfCl4 solution, the precursor was effectively decomposed with low annealing temperature of 150 °C. Thus it is preferable to use this solution for dielectric coating on flexible substrates. To achieve conformal coating on substrate, formic acid as a cosolvent was added to aqueous ink solution to reduce surface tension of the solution. Due to improved coating quality of HfO2 thin film, the fabricated HfO2 gate dielectric shows reliable breakdown characteristics and low leakage current.

Distribution of A118G single nucleotide polymorphism (SNP) in the mu-opioid receptor 1 gene (OPRM1) differs with ethnicity. We assessed the distribution of this SNP in Korean women with breast cancer and compared it with that in women of other ethnicities with breast cancer. Distribution of SNP genotypes was as follows: 49.8% for AG genotype, 40.6% for AA genotype, and 9.6% for GG genotype. Logistic regression analysis showed a negative association between the presence of the G allele at position 118 of OPRM1 and breast cancer in the studied population (odds ratios [OR], 0.635; p=0.002). However, the AG and GG genotypes were not associated with breast cancer in the studied population (OR, 0.719; p=0.130). The proportions of the AG and GG genotypes of the OPRM1 SNP were higher in Korean women with breast cancer than in those of other ethnicities.

We demonstrated solution-processed thin film transistors on a peroxo-zirconium oxide (ZrO(2)) dielectric with a maximum temperature of 350 °C. The formation of ZrO(2) films was investigated by TG-DTA, FT-IR, and XPS analyses at various temperatures. We synthesized a zirconium oxide solution by adding hydrogen peroxide (H(2)O(2)). The H(2)O(2) forms peroxo groups in the ZrO(2) film producing a dense-amorphous phase and a smooth surface film. Because of these characteristics, the ZrO(2) film successfully blocked leakage current even in annealing at 300 °C. Finally, to demonstrate that the ZrO(2) film is dielectric, we fabricated thin-film transistors (TFTs) with a solution-processed channel layer of indium zinc oxide (IZO) on ZrO(2) films at 350 °C. These TFTs had a mobility of 7.21 cm(2)/(V s), a threshold voltage (V(th)) of 3.22 V, and a V(th) shift of 1.6 V under positive gate bias stress.

A compartmentalized multidomain alignment state of a layer of liquid crystal display is achieved using an ultrathin, highly transparent, and ultrafast-responsive alignment layer fabricated by a simple method. The ultrathin alignment layer consists of a self-assembled oligomer layer of poly(dimethylsiloxane) (PDMS) formed by utilizing the oligomers that diffuse out from a PDMS elastomer stamp during a contact printing process.

Context: In Korea, where PTC comprises about 90–95% of the reported thyroid cancers, the prevalence of BRAFV600E mutation in papillary thyroid carcinoma (PTC) is above 80%. Objective: We analyzed the surgical result according to a management guideline based on the BRAFV600E mutation status of thyroid nodules. Design: A total of 865 thyroid nodules were prospectively analyzed for their cytology and BRAFV600E mutation status by pyrosequencing. For the patients who had a diagnosis of atypical cells of undetermined significance (ACUS), we recommended surgery when there was positivity for BRAFV600E mutation or the nodules were clinically suspicious. Results: Among 865 cases, 504, 141, 54, 140, 10, and 16 were diagnosed as benign, ACUS, suspicious for malignancy, malignant, suspicious for follicular neoplasm, and nondiagnostic, respectively. None of the 504 benign, 45 (31.9%) of the 141 ACUS, 46 (85.2%) of the 54 suspicious for malignancy, 129 (92.1%) of the 140 malignant, and one (10%) of the 10 suspicious for follicular neoplasm cases showed BRAFV600E mutation. Surgery was recommended to all 45 patients with BRAFV600E mutation-positive ACUS nodules; among them, 30 patients underwent surgery, 29 had PTC, and one had nodular hyperplasia. All the patients diagnosed as suspicious for malignancy or malignant were advised to undergo an operation, and they turned out to have PTCs regardless of their BRAFV600E mutation status. Conclusions: We found that performing BRAFV600E mutation analysis on the fine-needle aspiration biopsy specimens was of great help to make a therapeutic decision for thyroid nodules when the fine-needle aspiration biopsy results were equivocal.

We examined the effects of Rhizoma Dioscoreae Tokoronis extracts (RDTEs) on plasma lipids, body weight, and lipogenic enzymes. Mice were administered a standard chow diet, a 60% high-fat diet, or a high-fat diet with RDTE. Mice that were fed a high-fat diet containing RDTE were found to have lower increases in body and epididymal adipose tissue weights and a lessened occurrence of hepatic steatosis than mice that were fed a high-fat diet. The decreased adiposity that was induced by RDTE accounted for lower plasma levels of tumor necrosis factor-alpha, leptin, and glucose and a higher level of adiponectin. RDTE administration also resulted in a significant decrease in triglyceride, total plasma cholesterol, and low-density lipoprotein-cholesterol when compared to the high-fat group. To identify the mechanism by which RDTE induced its antiobesity effect, we investigated the sterol response element binding protein (SREBP) transcription system, which was induced in mice that were fed the high-fat diet. RDTE was found to suppress the expression of SREBP-1 as well as that of fatty acid synthase in adipose and liver tissues in mice provided the high-fat diet. These findings suggest that the antiobesity action of RDTE in mice that are fed a high-fat diet may occur in response to suppression of the SREBP-1-dependent lipogenic pathway.

We introduce an easy process for the fabrication of solution-processed indium oxide (InO) thin film transistors (TFTs) by heating a precursor solution. InO TFTs fabricated from solutions of an InO precursor heated at 90 °C had the highest mobility of 4.61 cm2 V−1 s−1 after being annealed at 200 °C. When the InO precursor solution is heated, HNO3 may be thermally evaporated in the InO precursor solution. Nitrogen atoms can disrupt hydrolysis and condensation reactions. An InO thin film deposited from a solution of the heated InO precursor is advantageous for hydrolysis and condensation reactions due to the absence of nitrogen atoms.

In this study, we present a simple process for the fabrication of aqueous-solution-processed metal oxide thin-film transistors (TFTs) via the manipulation of precursor solution temperature. Indium oxide TFTs fabricated from a solution of indium nitrate at 4 °C exhibited the highest mobility of 2.73 cm2/(Vs) at an annealing temperature of 200 °C. When the temperature of the metal oxide precursor solution is 4 °C, metal cations within the solution can be fully surrounded by H2O molecules owing to the high dielectric constant of H2O at low temperatures. These metal complexes are advantageous for the conversion of metal oxides via thermally driven hydrolysis and condensation processes due to their high potential energies. The same techniques have been applied successfully with high-order metal oxides including indium zinc oxide, indium gallium oxide, and indium gallium zinc oxide.

e11585 Background: We compared the survival of patients with Stage IIIB and Stage IIIC tumors and evaluated the prognosis of N3 and T4 to determine the criteria for an update of the classification ...

Purpose: Differentiated thyroid cancer has a good prognosis and high incidence in young women. Since endoscopic techniques were first recorded in 1996, surgical indications of endoscopic thyroidectomy have broadened. Therefore, the aim of this study is to investigate the usefulness of endoscopic thyroidectomy in clinically lymph node negative (cN0) thyroid cancer patients, based on oncologic completeness and safety, considering cosmetic outcomes. Methods: From July 2009 to June 2011, a total of 166 cases had undergone endoscopic thyroidectomy using the BABA (bilateral axillo-breast approach) method or conventional open thyroidectomy by one surgeon. Finally, excluding 72 patients, 94 patients with cN0 thyroid cancer were divided into two groups according to operative methods and analyzed to compare differences between the two methods retrospectively (endoscopic group, n = 49; conventional open group, n = 45). Results: We practiced comparative analysis for clinicopathologic characteristics, surgical outcomes including postoperative complications, and recurred cases during follow-up periods of each group. The results showed there was a tendency for patients, young, women rather than men, and having small size of thyroid cancer, to prefer endoscopic surgery to open surgery. Meanwhile, in postoperative complications, there were no statistically significant differences. During short followup periods, no recurrence or mortality case was observed. Conclusion: Endoscopic thyroidectomy is a feasible and safe method for the treatment of clinically lymph node negative (cN0) thyroid cancer.

We fabricated solution-processed gallium-doped indium oxide (GIO) thin-film transistors (TFTs) and performed hydrogen peroxide (H2O2) vapor treatment at 350 °C. We demonstrated that H2O and H2O2 vapor treatment enhanced the performance of the GIO TFTs. The GIO TFT only annealed in ambient air at 350 °C performed very poorly, whereas those annealed in air with H2O2 and H2O vapor at 350 °C exhibited significantly improved electrical performance. In particular, the H2O2-vapor-treated GIO TFTs had a mobility of 3.22 cm2 V−1 s−1. We believe that this method can help decrease the annealing temperature in order to obtain high-performance GIO TFTs.

Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasingly important in biology and medicine, because this technology can detect the relative abundance and spatial distribution of interesting proteins in tissues. Five thyroid cancer samples, along with normal tissue, were sliced and transferred onto conductive glass slides. After laser scanning by MALDI-TOF equipped with a smart beam laser, images were created for individual masses and proteins were classified at 200-µm spatial resolution. Based on the spatial distribution, region-specific proteins on a tumor lesion could be identified by protein extraction from tumor tissue and analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, various intensities of a specific peak were detected in the tumor and normal regions of the thyroid. Differences in the molecular weights of expressed proteins between tumor and normal regions were analyzed using unsupervised and supervised clustering. To verify the presence of discovered proteins through IMS, we identified ribosomal protein P2, which is specific for cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis of tissue sections, and identified the tumor-specific protein ribosomal protein P2. Graphical Abstract Keywords: Pathology, Proteins, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Thyroid Gland, Neoplasms INTRODUCTION Papillary thyroid carcinomas (PTC) are the most common form of thyroid cancer, accounting for nearly 85% of primary thyroid malignancies. Commonly, the solitary nodule is a palpably discrete swelling within an otherwise apparently normal thyroid gland, and is incidentally detected by radiological evaluation (1). From a clinical standpoint, the possibility of neoplastic disease is a major cause for concern in patients who present with thyroid nodules, because most conventional papillary carcinomas present as asymptomatic thyroid nodules. Recent studies have demonstrated 2 molecular mechanisms that function in the carcinogenesis of thyroid cancer: the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/Akt pathways (2, 3). Additionally, such pathways are related to genetic alterations such as rearrangements in the "rearranged during transfection" (RET) or neurotrophic tyrosine kinase receptor 1 (NTRK1) genes, and the activation of point mutations in the BRAF gene (4). In a previous study, protein expression patterns according to genetic variables have been demonstrated to correlate with the microscopic features, clinical manifestations, and prognostic characteristics of PTC (5). Although various protein alterations have been detected as diagnostic markers or prognostic predictors, the challenge remains to identify the expression of new molecules in tumors. In biological research, protein expression profiling technology is a useful method to identify differential protein expression patterns and modifications. Analytical techniques with high sensitivity and increased throughput are required for the discovery of new biomarkers and new drugs. Recent progress in imaging mass spectrometry (IMS) has made it possible to identify several cellular components such as proteins, drugs, and other endogenous molecules directly on tissue sections (6, 7, 8, 9, 10). IMS uses matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) technology. The matrix is applied on cryosectioned tissue and a very small area of the matrix-applied tissue is analyzed using MALDI-MS. Differences between the analyzed areas are displayed by the imaging program. Each analyzed area of the tissue section, which can be as small as >200 µm, on a conductive surface such as gold-plated or indium tin oxide (ITO)-coated slide, is analyzed spot by spot using MALDI-MS after the application of the matrix. Using all the spectral data from each spot, the magnitudes of specific peaks on each spot can be displayed in terms of color intensity. In this way, spatial information on the tissue can be obtained. Based on the spatial distribution, region-specific proteins on a tissue can be identified by extracting proteins from the tissue, digesting them with trypsin, and analyzing the fragments using liquid chromatography with tandem MS (LC-MS/MS). This technology using IMS has broad applications in the detection of new proteins in various fields. Compared with conventional imaging methods, the advantages of IMS are that it does not require the additional use of a specific antibody against the protein, and that it integrates histopathology and protein expression (11). For this reason, IMS provides superior information regarding distinct molecular arrangements in tissue sections. In the present study, we attempted to analyze thyroid samples, including those from PTC, using IMS. Before analysis using IMS, the diagnosis was confirmed by microscopic evaluation, immunohistochemical (IHC) staining of markers such as CK19, galectin-3, and RET, and pyrosequencing of the BRAF mutation, and then 5 homogenous samples of PTC were selected. After comparison of the differential molecular weight distribution between normal and tumor tissues using IMS, a protein of a specific molecular weight was identified by sequencing combined with LC-MS/MS, and then the presence of this protein was reconfirmed by western blot analysis.

In this study, we reported a 36% improvement in the performance of inverted solar cells as a result of increased short-circuit current (JSC) obtained using a composition of zinc oxide (ZnO) and reduced graphene oxide (RGO) as an n-type buffer layer. RGO-ZnO nanocomposites show higher electron conductivity than intrinsic ZnO; moreover, they show reduced contact resistance at the interface between the active layer and n-type buffer layer. These factors prevent carrier loss resulting from defects and recombinations in the device, thereby significantly increasing the JSC value for the device. Thus, an efficiency of 4.15% was achieved for inverted solar cells with a controlled RGO-ZnO nanocomposites layer.

A solution-processed ionic amorphous Al2O3 dielectric with a low temperature annealing process at 350 °C shows good compatibility and high performance in metal oxide semiconductor thin film transitors (TFTs) such as Li–ZnO TFTs and In–ZnO TFTs. The Li–ZnO/Al2O3 and In–ZnO/Al2O3 TFTs, with solution-processability and low temperature annealing at a maximum of 350 °C, exhibited field-effect mobilities of 46.9 cm2 V−1 s−1 in crystalline Li–ZnO/Al2O3 TFTs and 44.2 cm2 V−1 s−1 in amorphous In–ZnO/Al2O3 TFTs with an on/off current ratio of more than 105. The proton mobile ion, such as hydrogen ion (H+) from chemisorbed water, in the ionic Al2O3 dielectric remarkably induces a high performance capacitance by the formation of an electrical double layer. The chemisorbed water was monitored by FT-IR and ellipsometric porosimetry measurements. Furthermore, the addition of H2O2 to the ionic Al2O3 dielectric precursor successfully suppressed the oxygen vacancies in the dielectric layer, which caused the electrical trap and pass, and confirmed the stable operation. These ionic amorphous Al2O3 dielectrics show good potential as switching TFTs devices in advanced displays, because they can satisfy the various demands of next-generation high-performance TFTs, such as low-cost, solution-processability, and a relatively low-temperature process.

A low-temperature, solution-processed high-k HfO2 gate dielectric was demonstrated. To decompose a hafnium precursor at a temperature lower than 200 °C, an aqueous solution of HfCl4 was used because the strongly hydrated hafnium precursor was decomposed at a much lower temperature than anhydrous or partially hydrated hafnium chloride. No hazardous organic material was required in the low-temperature HfO2 coating process. Thus this precursor solution is environmentally safe and it is preferable to use this solution for gate dielectric coating on flexible substrates. The fabricated HfO2 gate dielectric shows reliable breakdown characteristics and high dielectric constant. We fabricated a thin film transistor (TFT) device with this gate dielectric and a maximum processing temperature of 150 °C for all the components of the TFT. The ZnO TFT on the HfO2 gate dielectric shows field-effect mobility of 1.17 cm2 V−1 s−1 and threshold voltage of 5.87 V. These results demonstrate the potential of our HfO2 thin film for flexible electronic device fabrication.

We fabricated alkaline-earth metal doped indium oxide thin-film transistors (TFTs) using a solution process. To analyze the effects of Mg, Ca, and Sr on the solution-processed indium oxide TFTs, thermogravimetric analysis, X-ray diffraction, atomic force microscopy analysis, and X-ray photoelectron spectroscopy were performed. The main difference in electrical performance results from the dehydroxylation energy of alkaline-earth metal, each ion radius and optical band gap. The optimized Mg-, Ca-, and Sr-doped indium oxide TFTs show mobilities of 2.03, 1.64, and 1.08 cm2 V-1 s-1, respectively, and an on-off current ratio of about ~105.

In this study, we fabricated zinc tin oxide (ZTO) thin-film transistors (TFTs) using a sol–gel solution at a low annealing temperature of 350 °C. We found that the combination of conventional hot plate annealing and microwave irradiation was effective for achieving high performance of ZTO-TFTs. Solution-processed ZTO-TFTs prepared at 350 °C by microwave irradiation showed enhanced device characteristics of 1.84 cm2 V-1 s-1 mobility and a 106 on/off current ratio. X-ray photoelectron spectroscopy analyses confirmed that residual hydroxyls in solution-processed ZTO films can be decomposed at low temperatures by microwave irradiation. Low-temperature microwave-assisted processing makes ZTO TFTs promising for use in flexible, transparent electronics.

We have shown previously that hypoxia activates the cyclin D1 promoter via the Jak2/STAT5b pathway in breast cancer cells. Most solid tumors contain hypoxic components and overexpression of cyclin D1. The purpose of the present study was to investigate the molecular mechanism by which momilactone B exerts its inhibitory effects on breast cancer cells. Momilactone B, extracted from Korean rice hulls, suppressed hypoxia-induced increases in phospho-STAT5, STAT5b, cyclin D1, and cdk4 protein levels in human breast cancer cells. STAT5b expression was inhibited by siRNA experiments leading to decreased cyclin D1. The effects of momilactone B on cell growth and apoptosis-related gene expression were investigated in breast cancer cells under hypoxic conditions (2% O2). Bax and p21 expression was found to be up-regulated, whereas ppRb and bcl-2 were down-regulated in momilactone B-treated cells under hypoxic conditions. However, the p53 protein level did not change. Flow cytometry with Annexin-FITC staining showed that the number of apoptotic cells increased in hypoxic cells treated with momilactone B compared with untreated hypoxic cells. Furthermore, caspase activity increased upon treatment with momilactone B under hypoxic conditions. These results indicate that momilactone B inhibits the growth of breast cancer cells, regulates the expression of apoptosis-related genes, and induces apoptosis through STAT5b and a caspase-3 dependent pathway. We suggest that momilactone B accelerates hypoxia-induced apoptosis of human breast cancer cells through STAT5b, and may represent an effective chemopreventive or therapeutic agent against breast cancer.

Purpose: Anal manometry is one of the most commonly used tests to evaluate fecal continence function. Advanced pressure parameters of the tests, such as fatigue rate index (FRI), resting rectoanal pressure gradient (RPG), cough index (CI), and radial asymmetry (RA) are recently devised to make up the inaccuracy of conventional parameters, but without solid verification. The object of this study is to investigate such parameters including conventional ones in incontinent patients compared with those in controls and to determine the significance of each parameter. Methods: Forty-four patients with anal incontinence and 42 controls were studied. We examined conventional pressure parameters (mean resting pressure [MRP], maximum squeeze pressure [MXSP]) and advanced parameters (RPG, FRI, CI, RA), and compare those parameters with normal controls. Multiple logistic regression analysis and receiver operating characteristic curve analyses were also performed. Results: No difference was detected in demographic factors between the two groups. Basic manometric parameters were significantly different between the two groups (MRP, 31.120.7 mmHg vs. 41.418.6 mmHg, P=0.0170; MXSP, 203.1 84.3 mmHg vs. 258.5105.9 mmHg, P=0.0086). Among advanced parameters, RPG and FRI were significantly different (2.831.54 vs. 4.081.53, P=0.0003; 921.6 sec vs. 75.6±12.1 sec, P=0.0333), but CI and RA were not so different (0.740.45 vs. 0.610.33, P=0.1326; 22.77.0% vs. 21.17.6%, P=0.3244). Only RPG was significant in multiple logistic regression analysis (P=0.019). Areas under ROC curves were 0.65 for MRP, 0.65 for MXSP, 0.82 for RPG, and 0.73 for FRI. Conclusion: Among anal manometric pressure parameters, RPG and FRI as advanced parameters are more accurate than any other parameters in detecting fecal incontinence.

Purpose: In recent studies, laparoscopic appendectomy has been widely performed for not only uncomplicated appendicitis but also perforated appendicitis. But, in children, the value of laparoscopic appendectomy for acute appendicitis is not yet established. Our retrospective study is to evaluate the safety of laparoscopic surgery for acute appendicitis in children. Methods: We reviewed electronic medical records of a total of 595 patients (95 children and 500 adults), who had been operated upon for acute appendicitis, from August 2005 to February 2007. Those patients were divided into two groups; children and adults. Demographic data, duration of pain, diagnostic methods, length of stay, operative time, time under anesthetic, time to diet, perforation rate, and complication rates were analyzed. Results: In eight adult patients, laparoscopic surgery was converted to open laparatomy. There was no significant difference in perforation rates (children 20.0% vs. adults 18.1%, P=0.714). However, postoperative complication rates were significantly higher in the children group (7.4%) compared to the adult group (2.2%). Conclusion: We noted that laparoscopic appendectomy should be applied cautiously, especially in pediatric groups due to the relatively high complication rate. However, we need to see more high-quality randomized trials.

14503 Background: The BRCA1 has an important role in the processing of DNA damage. This study was conducted to know whether germ-line variations of BRCA1 affect outcome of NSCLC patients treated wi...

Purpose: Currently, various tools are used for the diagnosis of nonrelaxing puborectalis syndrome (NRPRS), one of major causes of chronic constipation. Defecography, electromyography (EMG), balloon expulsion test, and a colon transit time study one examples of such tools, but none can be said to be the most accurate and effective one. A diagnosis is only made when two or more examinations show positive findings simultaneously. The aim of this study is to assess the correlation between EMG and the manometric defecation index (DI), which is a relatively new parameter, for the diagnosis of NRPRS. Methods: Forty-two chronically cornstipated patients without any history of anal or abdominal surgery underwent both anorectal manometric and EMG tests. The manometric defecation index (DI) was defined as the ratio between the peak rectal pressure and the peak anal pressure when the pressures were measured simultaneously during push by the catheter with longitudinally arranged side holes. The ratio of EMG activity was defined as the ratio between the peak amplitude during push and the peak amplitude during rest when EMG activities were measured by using an anal plug electrode. The two variables were compared prospectively, and their correlation was analyzed. Results: The manometric DI and the ratio of EMG activit in 42 patients were 0.80±0.75 and 1.50±0.65, respectively. The correlation coefficient between the two variables was −0.50 (P= 0.001). Conclusions: The manometric DI and the ratio of EMG activit were correlated significantly. Therefore, it can be said that the anorectal manometric test can replace the EMG test for diagnosis of NRPRS, which has less convenient access for most colorectal surgeons.