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During X-ray free electron laser (XFEL) operation, electron beam parameters such as the correlated energy spread, which affects the self-amplified spontaneous emission (SASE) spectrum, should remain optimized for the best performance. However, the correlated energy spread often varies from the optimized condition owing to the drift of RF stations, even when a feedback system with low-level radio frequency is operating. Non-destructive correlated energy spread monitoring could offer a means to stabilize such variations and improve the performance of X-ray generation by maintaining the spectral quality. Herein, we investigated the feasibility of a non-destructive correlated energy spread monitor based on multi-stripline electrodes for use with the 200 pC electron beam at the Pohang Accelerator Laboratory XFEL (PAL-XFEL). Beam tracking and electromagnetic simulations indicated that the correlated energy spread up to approximately 0.1% could be measured without intercepting the beam at the bunch compressors of the PAL-XFEL. Through the 3D FEL simulation, we confirmed that keeping the SASE energy spectrum bandwidth to 0.05–0.15%, with a photon energy of 9.7 keV at the undulator, requires the correlated energy spread of the electron beam to be within 0.12–0.35% at the third bunch compressor. From the simulations, we conclude that the non-destructive correlated energy spread monitor based on multi-stripline electrodes is applicable to XFEL facilities and could serve as an effective optimization tool.

In this study, Pt/TiO2-R catalytic activity during carbon monoxide (CO) oxidation at room temperature (25 °C) was enhanced by the addition of antimony (Sb) as a promoter. Antimony increases the surface oxygen of TiO2, which causes the large amounts of oxygen vacancies at reduction condition. Metallic Pt sites that come into contact with oxygen vacancies cause significant electron donation between the metal and support to facilitate metal–support interaction effect. The improved metal–support interaction effect increased the electron density on the Pt sites of Pt/Sb/TiO2-R, and the redox properties were enhanced owing to the unstable surface state. In the results, CO oxidation activity and durability of Pt/Sb/TiO2-R were improved than Pt/TiO2-R by enhanced oxygen mobility at room temperature.

Matrix metalloproteinase 11 (MMP11), a member of the MMP family involved in the degradation of the extracellular matrix, has been implicated in cancer progression. Despite the stromal expression of MMP11 in breast cancer, the prognostic significance and role of MMP11 in immune or stromal cells of breast cancer remain unclear. Based on the immunohistochemical analysis of breast cancer tissues from 497 patients, we demonstrated that MMP11 expression in mononuclear inflammatory cells (predominantly macrophages) is an independent negative prognostic factor in breast cancer, whereas MMP11 expression in tumor cells and fibroblasts is not associated with patient survival. Enforced MMP11 expression in breast cancer cells did not promote cell proliferation and migration. However, MMP11-overexpressing macrophages enhanced the migration of HER2-positive (HER2+) breast cancer cells, recruitment of monocytes, and tube formation of endothelial cells. Furthermore, we found that the chemokine CCL2 secreted from MMP11-overexpressing macrophages activated the MAPK pathway via its receptor CCR2 in breast cancer cells, thereby promoting the migration of HER2+ breast cancer cells through MMP9 upregulation. We also found that MMP11 expression in macrophages was stimulated by MMP11-overepressing HER2+ breast cancer cells. Collectively, our findings provide evidence that MMP11 in macrophages may play a pro-tumoral role in HER2+ breast cancer through interaction with cancer cells, monocytes, and endothelial cells.

Although a certain proportion of intramucosal carcinomas (IMCs) of the stomach does metastasize, the majority of patients are currently treated with endoscopic resection without lymph node dissection, and this potentially veils any existing metastasis and may put some patients in danger. In this regard, biological markers from the resected IMC that can predict metastasis are warranted. Here, we discovered unique miRNA expression profiles that consist of 21 distinct miRNAs that are specifically upregulated (miR-628-5p, miR-1587, miR-3175, miR-3620-5p, miR-4459, miR-4505, miR-4507, miR-4720-5p, miR-4742-5p, and miR-6779-5p) or downregulated (miR-106b-3p, miR-125a-5p, miR-151b, miR-181d-5p, miR-486-5p, miR-500a-3p, miR-502-3p, miR-1231, miR-3609, and miR-6831-5p) in metastatic (M)-IMC compared to nonmetastatic (N)-IMC, or nonneoplastic gastric mucosa. Intriguingly, most of these selected miRNAs showed stepwise increased or decreased expression from nonneoplastic tissue to N-IMC to M-IMC. This suggests that common oncogenic mechanisms are gradually intensified during the metastatic process. Using a machine-learning algorithm, we demonstrated that such miRNA signatures could distinguish M-IMC from N-IMC. Gene ontology and pathway analysis revealed that TGF-ß signaling was enriched from upregulated miRNAs, whereas E2F targets, apoptosis-related, hypoxia-related, and PI3K/AKT/mTOR signaling pathways, were enriched from downregulated miRNAs. Immunohistochemical staining of samples from multiple institutions indicated that PI3K/AKT/mTOR pathway components, MAPK1, phospho-p44/42 MAPK, and pS6 were highly expressed and the expression of SMAD7, a TGF-ß pathway component, was decreased in M-IMC, which could aid in distinguishing M-IMC from N-IMC. The miRNA signature discovered in this study is a valuable biological marker for identifying metastatic potential of IMCs, and provides novel insights regarding the metastatic progression of IMC.

Although a certain proportion of intramucosal carcinomas (IMCs) of the stomach does metastasize, the majority of patients are currently treated with endoscopic resection without lymph node dissection, and this potentially veils any existing metastasis and may put some patients in danger. In this regard, biological markers from the resected IMC that can predict metastasis are warranted. Here, we discovered unique miRNA expression profiles that consist of 21 distinct miRNAs that are specifically upregulated (miR-628-5p, miR-1587, miR-3175, miR-3620-5p, miR-4459, miR-4505, miR-4507, miR-4720-5p, miR-4742-5p, and miR-6779-5p) or downregulated (miR-106b-3p, miR-125a-5p, miR-151b, miR-181d-5p, miR-486-5p, miR-500a-3p, miR-502-3p, miR-1231, miR-3609, and miR-6831-5p) in metastatic (M)-IMC compared to nonmetastatic (N)-IMC, or nonneoplastic gastric mucosa. Intriguingly, most of these selected miRNAs showed stepwise increased or decreased expression from nonneoplastic tissue to N-IMC to M-IMC. This suggests that common oncogenic mechanisms are gradually intensified during the metastatic process. Using a machine-learning algorithm, we demonstrated that such miRNA signatures could distinguish M-IMC from N-IMC. Gene ontology and pathway analysis revealed that TGF-β signaling was enriched from upregulated miRNAs, whereas E2F targets, apoptosis-related, hypoxia-related, and PI3K/AKT/mTOR signaling pathways, were enriched from downregulated miRNAs. Immunohistochemical staining of samples from multiple institutions indicated that PI3K/AKT/mTOR pathway components, MAPK1, phospho-p44/42 MAPK, and pS6 were highly expressed and the expression of SMAD7, a TGF-β pathway component, was decreased in M-IMC, which could aid in distinguishing M-IMC from N-IMC. The miRNA signature discovered in this study is a valuable biological marker for identifying metastatic potential of IMCs, and provides novel insights regarding the metastatic progression of IMC.

Metastatic or recurrent colorectal cancer (CRC) patients require systemic chemotherapy, but the therapeutic options of targeted agents remain limited. CRC patients with KRASor BRAFgene mutations exhibit a worse prognosis and are resistant to anti-EGFR treatment. Previous studies have shown that the expression of anti-apoptotic protein BCL-XLis increased in CRC patients with KRAS/BRAFmutations, suggesting BCL-XLas a therapeutic target for this subgroup. Here, we performed genome-wide CRISPR/Cas9 screens of cell lines with KRASmutations to investigate the factors required for sensitivity to BCL-XLinhibitor ABT-263 using single-guide RNAs (sgRNAs) that induce loss-of-function mutations. In the presence of ABT-263, sgRNAs targeting negative regulators of WNT signaling (resulting in WNT activation) were enriched, whereas sgRNAs targeting positive regulators of WNT signaling (resulting in WNT inhibition) were depleted in ABT-263-resistant cells. The activation of WNT signaling was highly associated with an increased expression ratio of anti- to pro-apoptotic BCL-2 family genes in CRC samples. Genetic and pharmacologic inhibition of WNT signaling using β-catenin short hairpin RNA or TNIK inhibitor NCB-0846, respectively, augmented ABT-263-induced cell death in KRAS/BRAF-mutated cells. Inhibition of WNT signaling resulted in transcriptional repression of the anti-apoptotic BCL-2 family member, MCL1, via the functional inhibition of the β-catenin-containing complex at the MCL1promoter. In addition, the combination of ABT-263 and NCB-0846 exhibited synergistic effects in in vivo patient-derived xenograft (PDX) models with KRASmutations. Our data provide a novel targeted combination treatment strategy for the CRC patient subgroup with KRASor BRAFmutations.

BackgroundSomatic mutations are a major driver of cancer development and many have now been identified in various cancer types, but the comprehensive somatic mutation status of the normal tissues matched to tumours has not been revealed.MethodWe analysed the somatic mutations of whole exome sequencing data in 392 patient tumour and normal tissue pairs based on the corresponding blood samples across 10 tumour types.ResultsMany of the mutations involved in oncogenic pathways such as PI3K, NOTCH and TP53, were identified in the normal tissues. The ageing-related mutational signature was the most prominent contributing signature found and the mutations in the normal tissues were frequently in genes involved in late replication time (p<0.0001). Variants were rarely overlapping across tissue types but shared variants between normal and matched tumour tissue were present. These shared variants were frequently pathogenic when compared with non-shared variants (p=0.001) and showed a higher variant-allele-fraction (p<0.0001). Normal tissue-specific mutated genes were frequently non-cancer-associated (p=0.009). PIK3CAmutations were identified in 6 normal tissues and were harboured by all of the matched cancer tissues. Multiple types of PIK3CAmutations were found in normal breast and matched cancer tissues. The PIK3CAmutations exclusively present in normal tissue may indicate clonal expansions unrelated to the tumour. In addition, PIK3CAmutation was appeared that they arose before the occurrence of the allelic imbalance.ConclusionOur current results suggest that somatic mutant clones exist in normal tissues and that their clonal expansion could be linked to cancer development.

Mosaicisms caused by postzygotic mutational events are of increasing interest because of their potential association with various human diseases. Postzygotic somatic mutations have not been well characterized however in terms of their developmental lineage in humans. We conducted whole-genome sequencing (WGS) and targeted deep sequencing in 15 organs across three developmental lineages from a single male fetus with polycystic kidney disease (PKD) of 21 weeks gestational age. This fetus had no detectable neurological abnormalities at autopsy but germline mutations in the PKHD1gene were identified that may have been associated with the PKD. Eight early embryonic mosaic variants with no alteration of protein function were detected. These variants were thought to have occurred at the two or four cell stages after fertilization with a mutational pattern involving frequent C>T and T>C transitions. In our current analyses, no tendency toward organ-specific mutation occurrences was found as the eight variants were detected in all 15 organs. However different allele fractions of these variants were found in different organs, suggesting a tissue-specific asymmetric growth of cells that reflected the developmental germ layer of each organ. This indicated that somatic mutation occurrences, even in early embryogenesis, can affect specific organ development or disease. Our current analyses demonstrate that multi-organ analysis is helpful for understanding genomic mosaicism. Our results also provide insights into the biological role of mosaicism in embryonic development and disease.

Matrix metalloproteinase 11 (MMP11), a member of the MMP family involved in the degradation of the extracellular matrix, has been implicated in cancer progression. Despite the stromal expression of MMP11 in breast cancer, the prognostic significance and role of MMP11 in immune or stromal cells of breast cancer remain unclear. Based on the immunohistochemical analysis of breast cancer tissues from 497 patients, we demonstrated that MMP11 expression in mononuclear inflammatory cells (predominantly macrophages) is an independent negative prognostic factor in breast cancer, whereas MMP11 expression in tumor cells and fibroblasts is not associated with patient survival. Enforced MMP11 expression in breast cancer cells did not promote cell proliferation and migration. However, MMP11-overexpressing macrophages enhanced the migration of HER2-positive (HER2+) breast cancer cells, recruitment of monocytes, and tube formation of endothelial cells. Furthermore, we found that the chemokine CCL2 secreted from MMP11-overexpressing macrophages activated the MAPK pathway via its receptor CCR2 in breast cancer cells, thereby promoting the migration of HER2+ breast cancer cells through MMP9 upregulation. We also found that MMP11 expression in macrophages was stimulated by MMP11-overepressing HER2+ breast cancer cells. Collectively, our findings provide evidence that MMP11 in macrophages may play a pro-tumoral role in HER2+ breast cancer through interaction with cancer cells, monocytes, and endothelial cells.

ObjectiveLipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH.DesignWild-type C57BL/6J mice were fed a high fat and high cholesterol diet (HFHCD) to induce NASH. Hepatic SMS1 and SMS2 expressions were examined in various mouse models including HFHCD-fed mice and patients with NASH. Pyroptosis was estimated by the generation of the gasdermin-D N-terminal fragment. NASH susceptibility and pyroptosis were examined following knockdown of SMS1, protein kinase Cδ (PKCδ), or the NLR family CARD domain-containing protein 4 (NLRC4).ResultsHFHCD increased the hepatic levels of SM and DAG while decreasing the level of phosphatidylcholine. Hepatic expression of Sms1but not Sms2was higher in mouse models and patients with NASH. FC in hepatocytes induced Sms1expression, and Sms1knockdown prevented HFHCD-induced NASH. DAG produced by SMS1 activated PKCδ and NLRC4 inflammasome to induce hepatocyte pyroptosis. Depletion of Nlrc4prevented hepatocyte pyroptosis and the development of NASH. Conditioned media from pyroptotic hepatocytes activated the NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) in Kupffer cells, but Nlrp3knockout mice were not protected against HFHCD-induced hepatocyte pyroptosis.ConclusionSMS1 mediates hepatocyte pyroptosis through a novel DAG-PKCδ-NLRC4 axis and holds promise as a therapeutic target for NASH.

Neuroendocrine carcinoma (NEC) is an aggressive malignant tumor that rarely arises from the gallbladder. Here, we investigated the clinicopathologic and immunohistochemical characteristics of 34 NECs of the gallbladder. The patients were predominantly women (68%) with a median age of 63 years (range, 37 to 82 y). NECs frequently occurred in the fundus (44%) as mass-forming lesions (66%). Histologically, 17 tumors were of small cell type, and another 17 were of large cell type. Twenty-three cases (68%) were associated with biliary intraepithelial neoplasia (38%) and intracholecystic papillary neoplasm (29%). The majority of tumors exhibited a diffuse growth pattern (74%), followed by organoid (24%) or scirrhous (2%) growth patterns. Histologic features related to neuroendocrine differentiation, such as nuclear molding (56%), perilobular pseudopalisading (18%), and rosette formation (15%), were identified. Immunohistochemically, cytokeratin 7 and 20 were expressed in 19 (56%) and 8 (24%) cases, respectively. Loss of Rb1 expression and concomitant overexpression of p16 were observed in 25 (74%) cases. No BRAFV600Emutations were identified in any of the 34 NECs. For survival analysis, the 1-, 3-, and 5-year overall survival rates were 64%, 35%, and 19%, respectively. In a multivariate analysis, the receipt of adjuvant chemoradiation therapy was identified as the only independent prognostic factor associated with the overall survival rate. The 1- and 3-year overall survival rates of patients with NECs were poorer for patients with poorly differentiated adenocarcinoma of the gallbladder (P<0.001). The complete resection and application of postoperative adjuvant therapy may influence a better clinical outcome in patients with NEC of the gallbladder.

Study design: Retrospective population-based cohort study Objectives: To evaluate the incidence of acute spinal cord injury (SCI) in South Korea, and the prescription rates and complications related to high dose methylprednisolone therapy. Setting: Health Insurance Review and Assessment Service (HIRA) data Methods: National database of the Korean HIRA between 2007 and 2017 was reviewed. To identify patients with acute SCI and the use of high dose methylprednisolone, International Classification of Disease revision codes, medical behavior codes and examination codes were used. Patients were grouped according to whether or not they received methylprednisolone therapy (MP group vs non-MP group). Results: The average age-adjusted incidence of acute SCI per 1,000,000 persons was 26.4 and the peak incidence was in the 50s overall. The methylprednisolone prescription rate was highest in 2012 (76%) and continued to decrease thereafter, being lowest in 2017 (41%). The MP group showed higher complication rates in terms of pneumonia (OR 1.8, 95% CI, 1.62–2.0), GI bleeding (OR 1.2, 95% CI, 1.05–1.38), and UTI (OR 1.68, 95% CI, 1.53–1.84). The average length of hospitalization was longer in patients who received methylprednisolone (26.5 days vs. 24.4 days, p&lt; 0.05). Conclusions: The average age-adjusted incidence of acute SCI for 11 years was 26.4 per 1,000,000 persons and highest in 50s. Strategies should be established, and national health resources should be allocated to prevent acute SCI from occurring in older people. The prescription rate of high dose methylprednisolone for acute SCI is decreasing in South Korea but it is still high.

We investigated the effects of phosphorus (P) on the catalytic activity and properties of V/W/Ti and V/Sb/Ce/Ti. As a result of investigating changes in the physicochemical properties of each catalyst added with P, in the V/W/Ti catalyst, P was bound to vanadium or tungsten in the form of PO3–(metaphosphate) and produced phosphate species. During this process, the Brønsted acid site on the catalyst surface was greatly increased, and the adsorption amount of ammonia of the catalyst was increased. However, the active site (V═O) and redox properties were reduced, which inhibited the reactivity of adsorbed ammonia, and as a result, the selective catalytic reduction (SCR) efficiency was decreased. In contrast, V/Sb/Ce/Ti catalysts preferentially produce Ce–phosphate and Sb–phosphate. In this process, the production of PO3–and the reduction of the active site were suppressed, indicating high P resistance. In addition, with a low P content, the redox properties were increased, such that the SCR activity was improved.

The effective delivery of light energy from the light source to the subject is essential for an increase of therapeutic usefulness in the photobiomodulation therapy. Here, we demonstrate the application-specific near-infrared (NIR) LED therapy system applicable to the mouse for brain repair. The proposed NIR LED therapy system especially employ the curved-shape NIR LED module and the LED dimmer for optimal transfer of the light energy to the mouse brain. The therapeutic effects are evaluated in mice with chronic cerebral hypoperfusion by the positron emission tomographic scans. In the near future, we would like to quantitatively validate the therapeutic effect of our proposed NIR LED therapy system on mice with brain injury and apply it to a human brain.

Radical cystectomy with preoperative cisplatin-based neoadjuvant chemotherapy (NAC) is the standard care for muscle-invasive bladder cancers (MIBCs). However, the complete response rate to this modality remains relatively low, and current clinicopathologic and molecular classifications are inadequate to predict NAC response in patients with MIBC. Here, we demonstrate that dysregulation of the glutathione (GSH) pathway is fundamental for MIBC NAC resistance. Comprehensive analysis of the multicohort transcriptomes reveals that GSH metabolism and immune-response genes are enriched in NAC-resistant and NAC-sensitive MIBCs, respectively. A machine-learning-based tumor/stroma classifier is applied for high-throughput digitalized immunohistochemistry analysis, finding that GSH dynamics proteins, including glutaminase-1, are associated with NAC resistance. GSH dynamics is activated in cisplatin-resistant MIBC cells, and combination treatment with a GSH dynamics modulator and cisplatin significantly suppresses tumor growth in an orthotopic xenograft animal model. Collectively, these findings demonstrate the predictive and therapeutic values of GSH dynamics in determining the NAC response in MIBCs.

Background:FGF19amplification is a relatively novel type of genetic aberration that has been proposed to be a driver of hepatocarcinogenesis. Selective inhibitors of FGFR4, a receptor of FGF19, have been developed as targeted therapies for hepatocellular carcinoma (HCC). Despite the role of FGF19in mediating HCC progression, the clinicopathological characterization of patients exhibiting FGF19amplification remains unclear. Immunohistochemical staining is the simplest and most widely used method of identifying aberrations in the FGF19gene, although its specificity is very low. Methods:This study investigated the prognostic significance of FGF19amplification in a large cohort of 989 HCC patients using fluorescence in situ hybridization (FISH), which has a high degree of specificity. In addition, FISH data from formalin-fixed, paraffin-embedded sections were compared with copy number variation (CNV) data obtained from fresh frozen sections to validate the use of FISH as a diagnostic tool. Results:FGF19amplifications were detected by FISH in 51 (5.15%) of the 989 patients, and were independently associated with poor survival and a higher risk of tumor recurrence, as well as with poor prognostic factors such as a high α-fetoprotein level, hepatitis B or C virus infection, a large tumor size, microvascular invasion, and necrosis. In addition, FGF19amplification was associated with TP53mutation, and was mutually exclusive with CTNNB1mutation. The results of the FISH and CNV analyses exhibited a significant concordance rate of 96% (κ = 0.618, p< 0.001). Conclusions:These data indicate that FGF19amplification represents a unique molecular subtype associated with poor prognostic characteristics, which supports the hypothesis that the FGF19-FGFR4signaling pathway plays an important role in hepatocarcinogenesis. We have also demonstrated that FISH is a viable alternative to CNV analysis, offering a number of advantages in the clinical setting.

Next-generation sequencing (NGS) panels are widely used for defining tumor mutation profiles and determining treatment approaches. We performed targeted NGS with 382 colorectal cancer genes with known microsatellite instability (MSI). After exclusion of germline alterations, the load of somatic mutations and small insertion/deletion (indel) alterations were determined. In the test set, 79 patients with 41 microsatellite-stable (MSS) and 38 MSI tumors were included. There were 120 MSS and eight MSI-high tumors in the validation set. The number of somatic mutations of whole samples were distinguished into three groups: mutant functional polymerase epsilon catalytic subunit, MSI, and MSS tumors. The median numbers of somatic and indel mutations in MSI tumors were higher. The indel mutation to whole mutation ratio (I index) was higher in MSI tumors. Hypermutation and low I index of polymerase epsilon catalytic subunit mutant tumors, a somatic mutation load cut-off of ≥40, and an I index of ≥9% were selected as the criteria for detecting MSI tumors with high sensitivity and specificity. With the analysis of alteration patterns of homopolymer genes, a higher median number of homopolymer mutations in MSI tumors was observed. Mutated homopolymer ≥5 was selected as the criterion for detecting MSI tumors. MSI in colorectal cancer can be detected by targeted NGS panels with high sensitivity and specificity using somatic mutation load and I index.

Purpose: This study aims to explore Accelerators and their practices in sustaining start-ups within their innovative programs for these companies based on the resource-based perspective. Moreover, with an ever-increasing demand for Accelerators amongst start-up companies, this study also demonstrates the importance of Accelerators, as it pertains to new venture creation. Design/methodology/approach: This research uses an exploratory case study approach to examine a comparative view of leading Accelerator companies in the USA and Korea based on resource support. Findings: The results of this study show that there are a number of differences between Accelerators of the two countries in terms of the resources they support for early-stage start-ups. The findings also show some similarities. However, in Korea, the Accelerator landscape is limited, where mentorship, resources and investments are not readily accessible, resulting in low success rates for Korean start-up companies. These limitations have had a negative trickle-down effect when providing entrepreneurs with strong access to resources and investors, which highly affects the success rates of early-stage start-ups. Practical implications: In terms of the resource-based theory, this study contributes to the growth of early start-ups by emphasizing the role of the accelerator and suggesting the extent and impact that entrepreneurs have access to resources and investors. Originality/value: With significant growth in start-ups around the world, the necessity for start-up funding and mentorship has increased drastically. Start-up companies need various types of assets, systems, knowledge and information to achieve their goals. In Accelerators, start-ups receive all the aforementioned resources while also improving their entrepreneurial skills. Start-up companies have many options in seeking investors who support both tangible and intangible resources to boost growth. While there is a wealth of information on traditional funding methods, there are few studies that shed light on the role of Accelerators from the resource-based point of view.

Next-generation sequencing (NGS) testing of formalin-fixed, paraffin-embedded (FFPE) tissues is widely used in clinical diagnosis. However, the failure of high-quality DNA library construction, a critical step for NGS, often limits NGS application for FFPE tissues, particularly for old FFPE tissues. The aim was to develop a high-quality DNA library construction method optimized for NGS of FFPE specimens. DNA library construction was developed for FFPE specimens by using S1 nuclease and compared with the Covaris method—the widely accepted DNA library construction protocol. The Covaris method includes a DNA shearing step with sonication to generate shortened DNA fragments. DNA shearing was found to be unnecessary, and S1 nuclease treatment only during genomic DNA extraction significantly improved the success rate of library construction from FFPE tissues. Moreover, poor-quality FFPE tissues that failed the Covaris method were rescued with the S1 method. Higher complexity was observed in DNA libraries constructed by the S1 method. Among 223 FFPE specimens, DNA libraries were successfully constructed for 134 cases with the Covaris method (60.0% success rate), whereas the success rate was 86.5% (193 of 223) with the S1 method (P = 5.255e−10). Furthermore, we were able to rescue 59 samples, including 25 primary lung cancers, from the 89 failed Covaris method cases. In conclusion, the S1 method is optimal for NGS testing of poor-quality FFPE specimens.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (EBV+-DLBLs) tend to occur in immunocompromised patients, such as the elderly or those undergoing solid organ transplantation. The pathogenesis and genomic characteristics of EBV+-DLBLs are largely unknown because of the limited availability of human samples and lack of experimental animal models. We observed the development of 25 human EBV+-DLBLs during the engraftment of gastric adenocarcinomas into immunodeficient mice. An integrated genomic analysis of the human-derived EBV+-DLBLs revealed enrichment of mutations in Rho pathway genes, including RHPN2, and Rho pathway transcriptomic activation. Targeting the Rho pathway using a Rho-associated protein kinase (ROCK) inhibitor, fasudil, markedly decreased tumor growth in EBV+-DLBL patient-derived xenograft (PDX) models. Thus, alterations in the Rho pathway appear to contribute to EBV-induced lymphomagenesis in immunosuppressed environments.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (EBV+-DLBLs) tend to occur in immunocompromised patients, such as the elderly or those undergoing solid organ transplantation. The pathogenesis and genomic characteristics of EBV+-DLBLs are largely unknown because of the limited availability of human samples and lack of experimental animal models. We observed the development of 25 human EBV+-DLBLs during the engraftment of gastric adenocarcinomas into immunodeficient mice. An integrated genomic analysis of the human-derived EBV+-DLBLs revealed enrichment of mutations in Rho pathway genes, including RHPN2, and Rho pathway transcriptomic activation. Targeting the Rho pathway using a Rho-associated protein kinase (ROCK) inhibitor, fasudil, markedly decreased tumor growth in EBV+-DLBL patient-derived xenograft (PDX) models. Thus, alterations in the Rho pathway appear to contribute to EBV-induced lymphomagenesis in immunosuppressed environments.

We studied the role of the additives trehalose and poly(vinyl pyrrolidone) in the physical and pharmacokinetic properties of peptide drug incorporated hyaluronic acid microneedles. Poly(vinyl pyrrolidone) increases the mechanical strength of microneedles and ameliorates drug bioavailability in vivo, suggesting that poly(vinyl pyrrolidone) can be a promising additive in the fabrication of peptide drug-encapsulated fully dissolving microneedles.

Video compression exploits statistical, spatial, and temporal redundancy, as well as transform and quantization. In particular, the transform in a frequency domain plays a major role in energy compaction of spatial domain data into frequency domain data. The high efficient video coding standard uses the type‐IIdiscrete cosine transform (DCT‐II) and type‐VIIdiscrete sine transform (DST‐VII) to improve the coding efficiency of residual data. However, the DST‐VIIis applied only to the Intra 4 × 4 residual block because it yields relatively small gains in the larger block than in the 4 × 4 block. In this study, after rearranging the data of the residual block, we apply the DST‐VIIto the inter‐residual block to achieve coding gain. The rearrangement of the residual block data is similar to the arrangement of the basis vector with a the lowest frequency component of the DST‐VII. Experimental results show that the proposed method reduces the luma‐chroma (Cb+Cr) BDrates by approximately 0.23% to 0.22%, 0.44% to 0.58%, and 0.46% to 0.65% for the random access, low delay B, and low delay P configurations, respectively.

Black ginseng has a more potent biological activity than non-steamed ginseng. We investigated the effects of long-term intake of dietary black ginseng extract (BG) on antioxidant activity in aged mice. We also compared the effects of BG on cognitive deficits with those of white ginseng extract (WG) and red ginseng extract (RG).

Diverticular bleeding is one of the most common etiologies of lower GI bleeding. Endoscopy is a useful tool in both diagnosis and therapeutic management. The endoscopic hemostatic methods included epinephrine injection, thermal coagulation, clipping or combination of them. The aim of this study was to evaluate the outcome of different type of hemostasis. We reviewed the medical record of all patients who underwent endoscopic therapy for diverticular bleeding from December 2000 to December 2011. We measured hemoglobulin before procedure, early rebleeding (< 30 days), late rebleeding (> 30 days), blood transfusion requirement, hospital stay and complication. In our hospital, acute lower GI bleeding leads to almost 600 patients in the past 10 years. We identified 21 patients who underwent endoscopic hemostatic treatment for the diverticular hemorrhage. Patients with epinephrine injection alone had one of thirteen with early rebleeding (< 30 days) and one of thirteen with late rebleeding (> 30 days). Patients with combination therapy (epinephrine injection combined with coagulation or clipping) had one of eight with early bleeding and two of eight patients had late bleeding. There was no significant difference between these two groups on early rebleeding and late rebleeding. In our series, epinephrine injection alone for diverticular hemorrhage seems to be non‐inferior to the combination therapy for providing good initial hemostasis and preventing recurrent bleeding. Copyright © 2017, The Gastroenterological Society of Taiwan, The Digestive Endoscopy Society of Taiwan and Taiwan Association for the Study of the Liver.

Irreversible electroporation has clinically been used to treat various types of cancer. A plan on how to apply irreversible electroporation before practicing is very important to increase the ablation area and reduce the side effects. Several electrical models have been developed to predict the ablation area with applied electric energy. In this experiment, the static relationship between applied electric energy and ablated area was mathematically and experimentally investigated at 10 hours after applying irreversible electroporation. We performed the irreversible electroporation on the liver tissue of Sprague Dawley rats (male, 8 weeks, weighing 250-350 g). The ablated area was measured based on histological analysis and compared with the mathematical calculation from the electric energy, assuming that the tissue is homogeneous. The ablated area increased with the increase in applied electric energy. The numerically calculated contour lines of electric energy density overlapped well with the apoptotic area induced by the irreversible electroporation. The overlapped area clearly showed that the destructive threshold of apoptosis between electrodes is electric energy density level of 5.9 × 105J/m3. The results of the present study suggested that the clinical results of the irreversible electroporation on a liver tissue could be predicted through mathematical calculation.

Unlike necrosis by thermal ablation, irreversible electroporation (IRE) is known to induce apoptosis by disrupting plasma membrane integrity with electric pulses while preserving the structure of blood vessels and bile ducts in liver tissue without a heat sink effect. This study aimed to investigate thermal damage and histopathological effects in the porcine liver by high-frequency electric pulses (5 kHz) which is much higher than the widely used 1 Hz. The electric field and thermal distributions of 5 kHz electric pulses were compared with those of 1 Hz in numerical simulations. 5 kHz-IRE was applied on pigs under ultrasound imaging to guide the electrode placement. The animals underwent computed tomography (CT) examination immediately and 1 day after IRE. After CT, IRE-treated tissues were taken and analyzed histologically. CT revealed that hepatic veins were intact for 1-day post-IRE. Histopathologically, the structure of the portal vein was intact, but endothelial cells were partially removed. In addition, the hepatic artery structure from which endothelial cells were removed were not damaged, while the bile duct structure and cholangiocytes were intact. The thermal injury was observed only in the vicinity of the electrodes as simulated in silico. 5 kHz-IRE generated high heat due to its short pulse interval, but the thermal damage was limited to the tissue around the electrodes. The histopathological damage caused by 5 kHz-IRE was close to that caused by 1 Hz-IRE. If a short-time treatment is required for reasons such as anesthesia, high-frequency IRE treatment is worth considering. Our observations will contribute to a better understanding of the IRE phenomena and search for advanced therapeutic conditions.

The present study is about pitch control system of a small wind turbine using hinge mechanism. Small wind turbines generally apply stall control method or breaking equipment over the rated wind speed by reason of price or efficiency. However we perform pitch control applying the hinge mechanism which is simpler than that of medium and large size wind turbines. The hinge mechanism is a kind of linkage. It is composed of a rotation motion part, a linear motion part and a connection part. Pitch angle is controlled by the rotation parts which are connection to blades. In order to determine relationship between the hinge links and pitch angle, kinematic analysis is performed. Also, we derive design specifications of the actuator which drives the hinge mechanism by the Jacobian analysis. Simulation using MATLAB analyses forces and velocities of the hinge type pitch control system. Finally, as applying it to a 20 kW small wind turbine, the performances are evaluated by wind tunnel test.

ABSTRACTKorea’s economic growth is a truly remarkable one from its very humble beginning. The development and growth of small and medium-sized enterprises (SMEs) and their government policy are briefly examined herein. In short, in the 1960s and 1970s, the government policy was to help the development of SMEs, but focused on the heavy and chemical industries. In the 1980s and 1990s, many SMEs became key suppliers of various parts in the growing automobile and electronics industries. In the 2000s, various policies and initiatives for SMEs led to an explosive increase and growth of venture businesses. In the 2010s, a ‘win–win’ growth philosophy between large companies and SMEs was actively sought through promotions of various policies. Also, numerous efforts were made to strengthen the innovative competency of SMEs, establish fair-trading order, protect SME business area, actively promote win–win growth strategy and support for strengthening SMEs’ autonomy.

A series of Pt/TiO2catalysts with various Pt particle sizes and valence states were prepared and tested for CO oxidation at room temperature. Field-emission transmission electron microscopy and X-ray photoelectron spectroscopy analyses confirmed that the activity of the Pt/TiO2catalyst was influenced by the particle size and valence state of the catalyst particles. Excellent CO oxidation activity was observed at room temperature using highly dispersed, small metallic Pt particles. Increasing the Ptmetallic/Pttotalratio resulted in an increase of turnover frequencies. According to the Fourier-transform infrared spectroscopy results, the linear CO species that was adsorbed on metallic Pt sites at 25 °C reacted with atmospheric O2and was easily desorbed. However, linear CO species adsorbed on PtOx(x≥ 2) sites was only desorbed at temperatures ≥100 °C, confirming the lack of CO oxidation activity at room temperature with ionic Pt catalysts.

Ginseng (Panax ginsengMeyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as “Shin-nong-bon-cho-kyung.” Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported.

In this study, a combined process for the removal of SO 2 , NO x , and particulates at low temperature was suggested to minimize the scale and maximize the removal efficiency of equipment. Based on the results of the activity test for each process, a combined system could be designed, and its performance was also evaluated. SO 2 , dust, and NO x removal efficiencies were 94.15, 99.98, and 92.51%, respectively. It is believed that the system suggested in this study will be a very useful and popular system to control the air pollutants from coal boilers. [ABSTRACT FROM AUTHOR]

Chong-Myung-Tang (CMT) is a multi-herbal formula that has been used to improve memory. However, the potential mechanism remains unknown. The present study investigated the effects of CMT (50, 100, and 200 mg/kg) on spatial memory of aged mice. The behavioral training tests indicated that 200 mg/kg CMT treatment can significantly improve spatial memory of aged mice in the Morris water maze. Moreover, cell survival was examined by injecting bromodeoxyuridine (BrdU) on the first three days. The result showed that 200 mg/kg CMT treatment significantly increased cell survival in the dentate gyrus. Cell proliferation was determined by injecting BrdU 2 h before the mice were killed. The result suggested that CMT treatments had no influence on cell proliferation in the dentate gyrus. Thus, an increase in cell survival in the dentate gyrus stimulated by CMT may be involved in the effect of CMT on spatial memory improvement.

One of the major challenges in prostate cancer research is to identify prognosticpredictive factors to distinguish aggressive disease from indolent one. To select prognosticpredictive markers of postoperative biochemical recurrence (BCR) that could be easily performed in daily pathology practice, the expression of 6 immunohistochemical markers including zinc--2-glycoprotein (AZGP-1), hCAP-D3, mucin 1, vimentin, E-cadherin, and ERG was assessed in a tissue microarray of 400 radical prostatectomy specimens. The expression levels were correlated with clinicopathologic factors and BCR. During the median follow-up period of 55 months, BCR occurred in 70 cases (17.5). Low expression of AZGP-1 was noted in 76 cases (19.0), whereas high expression of hCAP-D3, mucin 1, vimentin, and ERG was observed in 205 (51.3), 81 (20.3), 33 (8.3), and 58 (14.5) cases, respectively. Aberrant E-cadherin expression was noted in 29 cases (7.3). By univariate analysis, BCR was associated with low expression of AZGP-1, high expression of hCAP-D3, and aberrant expression of E-cadherin. By multivariate analysis, only AZGP-1 remained an independent immunohistochemical factor, in addition to age, preoperative serum prostate-specific antigen level, Gleason score, tumor stage, and resection margin status. These results show that AZGP-1, hCAP-D3, and E-cadherin are potentially useful immunohistochemical markers to predict BCR, and that AZGP-1 can be used as an independent prognostic marker of aggressive prostate cancer.