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To evaluate potential viral contamination on the surfaces of personal protective equipment (PPE) in COVID-19 wards.Face shields, gloves, the chest area of PPE and shoe soles were sampled at different time points. The samples were tested for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR, and the cycle threshold (CT) values were recorded.The positive rate was 74.7% (239/320) for all PPE specimens. The CT values of the samples were ranked in the following order: face shieldschestsglovesshoe soles (37.08±1.38, 35.48±2.02, 34.17±1.91 and 33.52±3.16, respectively; P for trend.001). After disinfection, the CT values of shoe soles decreased compared with before disinfection (32.78±3.47 vs. 34.3±2.61, P = .037), whereas no significant effect of disinfection on the CT values of face shields, chests and gloves was observed. After disinfection, the CT values of specimens collected from shoe soles gradually increased; before disinfection, the CT values of shoe sole specimens were all less than 35.SARS-CoV-2 can attach to the surfaces of the PPE of healthcare professionals in COVID-19 wards, especially the shoe soles and undisinfected gloves. Shoe soles had the highest SARS-CoV-2 loads among all tested PPE items.

The use of Bcl-2 inhibitor Venetoclax (VEN) combined with hypomethylating agents or chemotherapy has shown efficacy in treating acute myeloid leukemia (AML) as frontline treatment and for relapse, allowing more patients to bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the influence of VEN-based therapy on the prognosis of subsequent allogeneic HSCT remains unknown. We retrospectively collected data from patients who proceeded to allo-HSCT between November 2018 and November 2020 after VEN-based therapy at five transplant centers in Zhejiang Province, China. A total of 39 patients were analyzed. Thirty-one patients were diagnosed with AML (28 de novo, 3 secondary to MDS), 6 with MDS, and 2 with CMML. The majority (74.4%) of patients received VEN-based therapy for the treatment of relapse (38.5%) or refractory disease (35.9%); 5 (12.8%) received it as an initial treatment, and 5 (12.8%) patients who were already in complete remission (CR) received VEN for further consolidation or deep remission before HSCT. Twenty-seven (69.2%) patients were in CR at the time of HSCT. Day + 100 cumulative incidences of grade I-IV acute graft-versus-host disease (aGVHD) and grade II-IV aGVHD were 43.6% and 15.4%, respectively. Of 34 evaluable patients, 6.4% and 25.6% developed chronic GVHD at 1 year and 2 years. The 100-day cytomegalovirus (CMV) reactivation occurred in 76.3% of patients and Epstein-Barr virus (EBV) reactivation occurred in 29.7% of patients. With a median follow-up of 14.7 months, overall survival, progression-free survival, relapse, and non-relapse mortality incidence at 1 year were 75.5%, 61.6%, 16.7%, and 21.7%, respectively. Both univariate and multivariate analysis revealed that relapsed/refractory (R/R) disease was associated with inferior PFS (HR 4.849, 95% CI 1.009-23.30; p = 0.049). Prior poor response to VEN was found to be a significant factor predicting higher risk of relapse (HR 4.37, 95% CI 1.130-16.9; p = 0.033). Our results showed that VEN-based regimen therapy followed by allo-HSCT in AML patients is feasible and does not increase the risk of transplant-related mortality and toxicity.

Supplementary Fig. 5. Kaplan-Meier analysis of the survival of patients with different mutations.

Legends for Supplementary Figures

Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targeted therapies. Here, we report the use of next-generation sequencing to interrogate the genetic and pathogenic mechanisms of 240 pediatric ALL cases with their matched remission samples. Commonly mutated genes fell into several categories, including RAS/receptor tyrosine kinases, epigenetic regulators, transcription factors involved in lineage commitment, and the p53/cell-cycle pathway. Unique recurrent mutational hotspots were observed in epigenetic regulators CREBBP (R1446C/H), WHSC1 (E1099K), and the tyrosine kinase FLT3 (K663R, N676K). The mutant WHSC1 was established as a gain-of-function oncogene, while the epigenetic regulator ARID1A and transcription factor CTCF were functionally identified as potential tumor suppressors. Analysis of 28 diagnosis/relapse trio patients plus 10 relapse cases revealed four evolutionary paths and uncovered the ordering of acquisition of mutations in these patients. This study provides a detailed mutational portrait of pediatric ALL and gives insights into the molecular pathogenesis of this disease. Cancer Res; 77(2); 390–400. ©2016 AACR.

Supplementary Fig. 4. p53 pathway is dysregulated in ALL.

Supplementary Fig. 2. Mutations found in the ASXL family of genes.

Supplementary Fig. 1. Mutational spectrum of pediatric ALL.

Supplementary Table 1. Samples used for whole exome and targeted sequencing. Supplementary Table 2. Clinical information of patients. Supplementary Table 3. 560 Genes screened in the targeted sequencing. Supplementary Table 4. Sequences of shRNA or CRISPR-Cas9 sgRNA used in this study. Supplementary Table 5. Sequences of real-time PCR primers used in this study. Supplementary Table 6. Sequences of primers used for Sanger validation of CRISPR-Cas9 indel. Supplementary Table 7. Mutations of KRAS identified in this study have been found in a variety of cancers. Supplementary Table 8. Mutations of PTPN11 in other cancers occurring in the same location as in our ALL cohort. Supplementary Table 9. Recurrent mutation sites of FLT3 in different cancers. Supplementary Table 10. Cell lines or cancer samples harboring either E1099K or T1150A hotspot mutation of WHSC1. Supplementary Table 11. R1446 mutations of CREBBP recurrently occurred in a variety of cancers. Supplementary Table 12. Mutational hotspot (D1399) of EP300 occurring in other cancers occurring in the same location as in our ALL cohort.Supplementary Table 13. Rare mutations occurring in our ALL cohort (mutated in one individual each), but these mutations have been recurrently documented in the COSMIC cancer mutations database. Supplementary Table 14. Mutations of genes involved in DNA repair pathway in relapse samples.

Supplementary Figure 2. Pathways regulated by PARK2 in glioma cells.

Supplementary Information includes Supplementary Materials and Methods, Supplementary Figure Legends and References. (FOR PUBLICATION)

Supplementary Figure 3. PARK2 interacts with multiple forms of β-catenin proteins.

Supplementary Figure 4. Wnt-β-catenin and EGFR-AKT pathways in glioma.

Supplementary Table 1.Summary of somatic PARK2 mutations. Supplementary Table 2. Sequences of shRNAs and siRNAs. Supplementary Table 3. Sequences of primers used for qRT-PCR.

PARK2 (PARKIN) is an E3 ubiquitin ligase whose dysfunction has been associated with the progression of Parkinsonism and human malignancies, and its role in cancer remains to be explored. In this study, we report that PARK2 is frequently deleted and underexpressed in human glioma, and low PARK2 expression is associated with poor survival. Restoration of PARK2 significantly inhibited glioma cell growth both in vitro and in vivo, whereas depletion of PARK2 promoted cell proliferation. PARK2 attenuated both Wnt- and EGF-stimulated pathways through downregulating the intracellular level of β-catenin and EGFR. Notably, PARK2 physically interacted with both β-catenin and EGFR. We further found that PARK2 promoted the ubiquitination of these two proteins in an E3 ligase activity-dependent manner. Finally, inspired by these newly identified tumor-suppressive functions of PARK2, we tested and proved that combination of small-molecule inhibitors targeting both Wnt–β-catenin and EGFR–AKT pathways synergistically impaired glioma cell viability. Together, our findings uncover novel cancer-associated functions of PARK2 and provide a potential therapeutic approach to treat glioma. Cancer Res; 75(9); 1815–27. ©2015 AACR.

Supplementary Figure 5. Dual inhibition of glioma cells with combinational use of MK2206 and ICG001.

Supplementary Figure 1. Prognostic value of PARK2 expression in GBM and ovarian serious cystadenocarcinoma.

This study adopts the paradigm of upper echelons theory (UET) and establishes a novel dataset covering the main characteristics of prefecture-level party secretaries in southwest China to investigate the association between local top officials’ traits and regional tourism economies. Empirical results show that a party secretary’s education and work experience significantly influence the development of regional tourism economies, and in most cases these influences are positive. These effects vary as the level of regional economic development and the quality of tourism resources change. These effects may be different for autonomous regions (for ethnic minorities) and non-autonomous regions. We find an inverted U-shaped relationship between the age of party secretaries and the performance of tourism economies. As an initial effort to identify the impact of regional officials, this study contributes to tourism economics and provides valuable implications for regional tourism development.

Esophageal squamous cell carcinoma (ESCC) is a lethal disease due to its high aggressiveness. The aim of the present study was to investigate the role of xeroderma pigmentosum complementation group D (XPD) in the growth and invasion of ESCC and to elucidate the potential underlying molecular mechanisms. Western blot analysis and RT‑qPCR were used to detect the expression level of XPD in ESCC tissue samples and adjacent normal esophageal tissue samples. The pEGFP‑N2/XPD plasmid was transfected into human ESCC cell lines (EC9706 and EC109). The proliferation, apoptosis, migration and invasion of EC9706 or EC109 cells were assessed following transfection with the XPD overexpression plasmid. The chemosensitivity of EC9706 or EC109 cells to cisplatin or fluorouracil was evaluated by CCK‑8 assay. The expression levels of phosphoinositide 3‑kinase (PI3K)/AKT, nuclear factor (NF)‑κB, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and mitogen‑activated protein kinase (MAPK) signaling pathway‑related genes were detected by RT‑qPCR and western blot analysis. The results demonstrated that the expression level of XPD was markedly lower in ESCC tissue samples than in adjacent normal esophageal tissue samples. The pEGFP‑N2/XPD plasmid was successfully transfected into EC9706 or EC109 cells, inducing XPD overexpression. A High XPD expression markedly suppressed cell proliferation, migration and invasion, and increased the apoptotic rate of EC9706 and EC109 cells. Furthermore, the overexpression of XPD significantly increased the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil. Following XPD overexpression, the expression levels of PI3K, p‑AKT, c‑Myc, Cyclin D1, Bcl‑2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)‑9 were markedly downregulated, while the expression level of p21 was markedly upregulated. On the whole, the findings of the present study demonstrate that XPD inhibits the growth and invasion of EC9706 and EC109 cells, whilst also enhancing the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil by regulating the PI3K/AKT signaling pathway. XPD may thus be an underlying target for ESCC treatment and drug resistance.

Functional supramolecular gel materials have potential applications in sensors, optical switches, artificial antennae, drug delivery and so on. In this paper, quinoline-cored poly(aryl ether) dendritic organogelators were designed, synthesized and fully characterized. The gelation behaviour of the dendritic organogelator was tested in organic solvents, mixed solvents and ionic liquids. The dendron Q-G1 was found to be an efficient and versatile organogelator toward various apolar and polar organic solvents with the critical gelation concentrations (CGCs) approaching 1.2×10-2 mol/L, indicating one dendritic organogelator could immobilize 1.2×103 solvent molecules in the organogel network. Interestingly, these dendrons exhibited excellent gel formation in ionic liquids. Notably, these dendritic organogels were found to display multiple stimuli-responsive properties toward external stimuli including heat, ultrasound and shear stress, with a reversible sol-gel phase transition. In addition, the dendritic organogel could effectively adsorb heavy metals and organic dyes. The removal rate of Pb2+ was up to 20% and the adsorption rate for Rhodamine B was as high as 89%.

Exploring the composition of soil organic carbon (SOC) and aggregate stability over a range of elevations is essential to evaluate the stability of SOC and the conversion of carbon source or sink of mountain ecosystems. However, information of those changes in mountain ecosystems in arid and semi-arid regions is still scarce to date. In this study, we estimated the response of SOC stability along elevation gradient (1,380–2,438 m) by combining physical protection of aggregates with chemical protection of SOC using a redundancy analysis method in the Helan Mountains, northwest China. Results showed that the dominated aggregates of Helan Mountains changed from microaggregates to macroaggregates with increasing elevation, and the mean weight diameter (MWD) in mid and high elevations (2,139–2,248 m) was significantly higher than that in low elevations (1,380–1,650 m). Solid-state 13C NMR spectra showed that O-alkyl C was the main chemical composition of SOC in the different elevations. Regression analysis indicated that with the increase of elevation, the proportion of aromatic C and aromaticity gradually increased, peaked at the mid elevation and subsequently decreased. These findings indicated that the soil structure and chemical composition of SOC are more stable in the mid elevation. Macroaggregates were positively correlated with O-alkyl C and aromatic C, while silt and clay were positively correlated with alkyl C, indicative of a lower decomposition rate of macroaggregates. The RDA analysis confirmed that aggregate stability were significant associated with SOC content and chemical composition such as O-alkyl C, indicating that the soil labile carbon pool was most related to affect aggregate stability. Our findings suggest that the Helan Mountains had a better soil structure and a more stable SOC chemical composition at mid elevation ranges. The soil structure at low elevations is sensitive to environment change; therefore, a reduction in anthropogenic disturbance is suggested for improved sustainability of the ecosystem.

Exploring the distribution patterns of soil nutrients in aggregates of forests along different altitudes in arid and semi-arid areas can provide a theoretical basis for understanding nutrient cycling in vulnerable mountain ecosystems. In this study, we analyzed the distribution and stability of aggregates in the 0-20 cm soil layer along different altitudes (1380-2438 m) of Helan Mountains and measured the storage and stoichiometric characteristics of organic carbon, total nitrogen, and total phosphorus in soil aggregates. Results showed that the main soil aggregates of Helan Mountains changed from micro-aggregates (0.25-0.053 mm) to macro-aggregates (0.25 mm) with increa-sing elevation. The mean weight diameter (MWD) and geometric mean diameter (GMD) of soil aggregates in high altitude (2139-2248 m) were significantly higher than those in low altitude (1380-1650 m). The content and storage of organic carbon and total nitrogen in soil aggregates of different size fractions were positively correlated with altitude, while the content of total phosphorus fluctuated with the increase in elevation and distributed uniformly in aggregates. Macro-aggregates and micro-aggregates had more contribution to soil nutrient storage than the silt and clay fractions, indicating that the proportion of aggregates with different size fractions was the key factor affecting soil nutrient storage and that macro-aggregates and micro-aggregates were the main carriers of soil nutrients. Moreover, the C:N ratio in aggregates of different size fractions did not change across different altitudes, whereas the C:P and N:P ratio were higher at mid and high elevations than those at low elevations. Our results indicated that the mid and high elevations of Helan Mountains had higher nutrient storage in the surface soil layer, and that higher content of macro-aggregates and micro-aggregates would help to retain organic carbon and nutrients in the soil. Soil nitrogen limitation was strong at low altitude in our study, suggesting that the appropriate amount of nitrogen addition in low altitudes could improve total nitrogen status during forest cultivation.探究干旱半干旱区山地森林生态系统不同海拔土壤养分在团聚体中的分布规律,可为理解脆弱山地生态系统养分循环提供理论依据。本研究以贺兰山不同海拔(1380～2438 m)土壤为对象,分析0～20 cm土层团聚体分布及其稳定性、不同粒级团聚体有机碳、全氮、全磷储量及其化学计量特征。结果表明: 随海拔升高贺兰山主要土壤团聚体由微团聚体(0.25～0.053 mm)转变为大团聚体(0.25 mm),平均重量直径(MWD)和几何平均直径(GMD)在高海拔样地(2139～2248 m)显著高于低海拔样地(1380～1650 m)。各粒级团聚体有机碳、全氮含量和储量随海拔升高呈增大趋势;全磷含量随海拔升高呈波动趋势,且在各粒级团聚体分布均匀。大团聚体和微团聚体对土壤养分具有更高的贡献率,各粒级团聚体比例是影响土壤养分的关键因素,大团聚体和微团聚体是土壤养分的主要载体。各粒级团聚体C∶N在不同海拔变化不显著,C∶P和N∶P在中高海拔显著高于低海拔。贺兰山中高海拔的表层土壤具有更高的养分储量,较高含量的大团聚体和微团聚体有助于有机碳和养分的固持,低海拔土壤氮素限制高,在森林培育过程中可通过适当添加氮肥以改善低海拔土壤全氮状况。.

Aim: To compare and evaluate the prognostic value of various pretreatment combinations of inflammatory factors in patients with lung cancer (LC). Materials & methods: This study enrolled 1005 patients with LC and categorized into a discovery cohort and a validation cohort. Results: A combination of Lymphocyte-to-C-reactive protein levels (LCR) demonstrated the highest correlation with poor first-line progression-free survival (PFS) and overall survival (OS) (p 0.05) compared with other parameters in LC patients. Decreased preoperative LCR was an independent prognostic factor for first-line PFS and OS (p 0.05) in patients. Conclusion: Pretreatment LCR is a promising biomarker for first-line PFS and OS in patients with LC.

Diagnosis and relapse: cytogenetically normal acute myelogenous leukemia without FLT3 -ITD or MLL -PTD

Hepatocellular carcinoma (HCC) is one of the primary causes of cancer-associated deaths worldwide. Current treatment methods include surgical resection, chemotherapy and radiotherapy; however the curative rate remains low, thus novel treatments are required. The aim of the present study was to investigate the role of targeting protein for Xenopus kinesin-like protein 2 (TPX2) in the growth of HCC and its underlying molecular mechanism. Immunohistochemistry staining, reverse transcription-quantitative (RT-q)PCR and western blotting were used to detect the expression of TPX2 mRNA and protein in liver cancer tissue samples, adjacent normal liver tissue samples, and the HCC cell lines Huh7, Hep3B, PLC/PRF/5 and MHCC97-H. The recombinant plasmid pMagic4.1-shRNA-TPX2 was constructed and transfected into Huh7 and Hep3B HCC cells to silence TPX2 expression. The proliferation, apoptosis, migration and invasion of Huh7 cells and Hep3B cells were evaluated before and after TPX2 silencing. The mRNA and protein expression levels of multiple signaling pathway-associated genes were detected by RT-qPCR and western blotting. The expression levels of TPX2 mRNA and protein were significantly higher in HCC tissue samples compared with adjacent normal liver tissue sample. TPX2 mRNA and protein expression levels were detected in the different HCC cell lines. The recombinant plasmid pMagic4.1-shRNA-TPX2 was successfully transfected into Huh7 and Hep3B cells, resulting in TPX2 silencing. TPX2 knockdown significantly reduced cell proliferation, cell migration and cell invasion of Huh7 and Hep3B cells, whilst also increasing the rate of apoptosis in these cells. Following TPX2 silencing, the expression levels of PI3K, phospho-AKT, Bcl-2, c-Myc and Cyclin D1 were significantly decreased, whereas the expression levels of P21 and P27 were significantly increased. In conclusion, TPX2 may suppress the growth of HCC by regulating the PI3K/AKT signaling pathway and thus, TPX2 may be a potential target for the treatment of liver cancer.

Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients.

Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. To identify the mutational spectrum associated with relapse, whole-exome sequencing was performed on 13 matched diagnosis, relapse, and remission trios followed by targeted sequencing of 299 genes in 67 FLT3-ITD patients. The FLT3-ITD genome has an average of 13 mutations per sample, similar to other AML subtypes, which is a low mutation rate compared with that in solid tumors. Recurrent mutations occur in genes related to DNA methylation, chromatin, histone methylation, myeloid transcription factors, signaling, adhesion, cohesin complex, and the spliceosome. Their pattern of mutual exclusivity and cooperation among mutated genes suggests that these genes have a strong biological relationship. In addition, we identified mutations in previously unappreciated genes such as MLL3, NSD1, FAT1, FAT4, and IDH3B. Mutations in 9 genes were observed in the relapse-specific phase. DNMT3A mutations are the most stable mutations, and this DNMT3A-transformed clone can be present even in morphologic complete remissions. Of note, all AML matched trio samples shared at least 1 genomic alteration at diagnosis and relapse, suggesting common ancestral clones. Two types of clonal evolution occur at relapse: either the founder clone recurs or a subclone of the founder clone escapes from induction chemotherapy and expands at relapse by acquiring new mutations. Relapse-specific mutations displayed an increase in transversions. Functional assays demonstrated that both MLL3 and FAT1 exert tumor-suppressor activity in the FLT3-ITD subtype. An inhibitor of XPO1 synergized with standard AML induction chemotherapy to inhibit FLT3-ITD growth. This study clearly shows that FLT3-ITD AML requires additional driver genetic alterations in addition to FLT3-ITD alone.

Protein structure prediction is a main task in the field of bioinformatics, and the prediction of protein secondary structure is the key point of this task. Extracting representative features and efficient classification methods are the basis of the prediction process. In this paper, a prediction method based on BP neural network is proposed. We use valid protein features extracted by variable-sized sliding window and two different encoding modes (5-bit encoding and Profile encoding) as input data, to make predictions for the secondary structure of proteins. The prediction accuracies are calculated by Jackknife test on three commonly used low-similarity protein datasets: 25PDB, 1189 and 640, and this method achieves a high overall accuracy upon these three datasets.

In order to filter out the PPI (protein-protein interaction) data noise and improve the accuracy of protein complexes prediction, this paper proposed a method to integrate biological information and topology information as the weight of the PPI network. There are also some traditional methods to deal with the data noise by topology information of biological information, but fewer of them integrate those two aspect. In this paper, we introduced a method to extract the feature vectors for protein couples or the interactions instead of single proteins based on both topology and biology information, then the cosine theory is used to measure the weight of PPI network. At last, it used four classical predicting protein complexes algorithms to detect protein complexes from different weighted PPI network. The result shows that our method performs better both on filtering out data noise and predicting protein complexes.

PARK2 (PARKIN) is an E3 ubiquitin ligase whose dysfunction has been associated with the progression of Parkinsonism and human malignancies, and its role in cancer remains to be explored. In this study, we report that PARK2 is frequently deleted and underexpressed in human glioma, and low PARK2 expression is associated with poor survival. Restoration of PARK2 significantly inhibited glioma cell growth both in vitro and in vivo, whereas depletion of PARK2 promoted cell proliferation. PARK2 attenuated both Wnt- and EGF-stimulated pathways through downregulating the intracellular level of β-catenin and EGFR. Notably, PARK2 physically interacted with both β-catenin and EGFR. We further found that PARK2 promoted the ubiquitination of these two proteins in an E3 ligase activity-dependent manner. Finally, inspired by these newly identified tumor-suppressive functions of PARK2, we tested and proved that combination of small-molecule inhibitors targeting both Wnt–β-catenin and EGFR–AKT pathways synergistically impaired glioma cell viability. Together, our findings uncover novel cancer-associated functions of PARK2 and provide a potential therapeutic approach to treat glioma. Cancer Res; 75(9); 1815–27. ©2015 AACR.

Through analyzing statistically the status of large-scale swine wastewater pollution in Poyang Lake basin, we indicated that high concentrations of pollutants such as organic matters, heavy metals, and antibiotics has potential damage to air, waters, and soil environments. Based on the inductive analysis on the these status and an existing process, the feasibility of the technology responding to the wastewater from small-sized, medium-sized, and large-sized swine farm was recommended.

We investigated the oncogenic role of SETDB1, focusing on non-small cell lung cancer (NSCLC), which has high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry; 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p

Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targeted therapies. Here, we report the use of next-generation sequencing to interrogate the genetic and pathogenic mechanisms of 240 pediatric ALL cases with their matched remission samples. Commonly mutated genes fell into several categories, including RAS/receptor tyrosine kinases, epigenetic regulators, transcription factors involved in lineage commitment, and the p53/cell-cycle pathway. Unique recurrent mutational hotspots were observed in epigenetic regulators CREBBP (R1446C/H), WHSC1 (E1099K), and the tyrosine kinase FLT3 (K663R, N676K). The mutant WHSC1 was established as a gain-of-function oncogene, while the epigenetic regulator ARID1A and transcription factor CTCF were functionally identified as potential tumor suppressors. Analysis of 28 diagnosis/relapse trio patients plus 10 relapse cases revealed four evolutionary paths and uncovered the ordering of acquisition of mutations in these patients. This study provides a detailed mutational portrait of pediatric ALL and gives insights into the molecular pathogenesis of this disease. Cancer Res; 77(2); 390–400. ©2016 AACR.

Procedures of thermal diffusion (TD) process are carried out on two specimens of Cr12MoV steel using the same salt bath formula. For the two specimens, the beginning V concentration, V concentration at the time specimen is added, are different, the level of which is controled by changing the interval between the specimen are added and the time reducing agent of Al meeting with vanadizing source of V2O5. The interval for Specimen 1 and Specimen 2 are 10 and 30 minutes respectively. Consequently, different changes are happened on the surface of the substrates. The microstructures of coatings are observed by optical metallographic microscope and SEM/EDS, the hardness are tested by Vickers micro-hardness tester. Results show that: VC coating formed on Specimen 2 is of better performances than Specimen 1, microhardness of Specimen 2 reaches as much as 2400HV. It can be concluded that level of V concentration at the beginning of TD process is a vital factor for the forming of VC layer.

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy having no effective treatment. Laminin subunit-γ-2 (LAMC2) is an epithelial basement membrane protein involved in cell migration and tumor invasion and might represent an ideal target for the development of novel therapeutic approaches for ATC.The objective of the investigation was to study the role of LAMC2 in ATC tumorigenesis.LAMC2 expression was evaluated by RT-PCR, Western blotting, and immunohistochemistry in tumor specimens, adjacent noncancerous tissues, and cell lines. The short hairpin RNA (shRNA) approach was used to investigate the effect of LAMC2 knockdown on the tumorigenesis of ATC.LAMC2 was highly expressed in ATC samples and cell lines compared with normal thyroid tissues. Silencing LAMC2 by shRNA in ATC cells moderately inhibited cell growth in liquid culture and dramatically decreased growth in soft agar and in xenografts growing in immunodeficient mice. Silencing LAMC2 caused cell cycle arrest and significantly suppressed the migration, invasion, and wound healing of ATC cells. Rescue experiments by overexpressing LAMC2 in LAMC2 knockdown cells reversed the inhibitory effects as shown by increased cell proliferation and colony formation. Microarray data demonstrated that LAMC2 shRNA significantly altered the expression of genes associated with migration, invasion, proliferation, and survival. Immunoprecipitation studies showed that LAMC2 bound to epidermal growth factor receptor (EGFR) in the ATC cells. Silencing LAMC2 partially blocked epidermal growth factor-mediated activation of EGFR and its downstream pathway. Interestingly, cetuximab (an EGFR blocking antibody) or EGFR small interfering RNA additively enhanced the antiproliferative activity of the LAMC2 knockdown ATC cells compared with the control cells.To our knowledge, this is the first report investigating the effect of LAMC2 on cell growth, cell cycle, migration, invasion, and EGFR signaling in ATC cells, suggesting that LAMC2 may be a potential therapeutic target for the treatment of ATC.

This paper studies the temperature field variation of the chain link as well as the stress and deformation distribution of the pin which works in hot forging and stamping production line with heat recovery function. The approach is to build the model of the chain link with Pro/Engineer and apply it to the simulation with Pro/Mechanica. To be specific, it is to stimulate the thermal conduction of the chain link and the stress state of the pin under high temperature with Pro/Mechanica-Thermal and Pro/Mechanica-Structure module, respectively. The results are the temperature filed nephogram of the chain link as well as the stress and deformation nephogram of the pin. The simulation shows that:1) the temperature reaches 420°C at the contacts of the outer and inner plates at 600s, 2) the maximum stress of the pin is 112Mpa at the ends where the pin meets the outer and inner plates,3) the pins max deformation is 0.0159mm at the middle of the pin. Comparing the simulation to the actual temperature at the contacts of the outer and inner plates,which is measured ten times in advance with average of 439°C ,the simulation is favorable. According to the results above, graphite lubrication should be chosen for the chain and the pin can work properly with deformation rate of 0.795. By this way of simulating with Pro/Mechanica, complicated calculations and repeated tests can be reduced largely, meanwhile, useful parameters and mathematical model can also be provided for manufacturing and process control.

Discovery of cancer genes through interrogation of genomic dosage is one of the major approaches in cancer research. In this study, we report that phosphodiesterase subtype 4D (PDE4D) gene was homozygously deleted in 198 cases of 5,569 primary solid tumors (3.56%), with most being internal microdeletions. Unexpectedly, the microdeletions did not result in loss of their gene products. Screening PDE4D expression in 11 different types of primary tumor samples ( n = 165) with immunohistochemistry staining revealed that its protein levels were up-regulated compared with corresponding nontransformed tissues. Importantly, depletion of endogenous PDE4D with three independent shRNAs caused apoptosis and growth inhibition in multiple types of cancer cells, including breast, lung, ovary, endometrium, gastric, and melanoma, which could be rescued by reexpression of PDE4D. We further showed that antitumor events triggered by PDE4D suppression were lineage-dependently associated with Bcl-2 interacting mediator of cell death (BIM) induction and microphthalmia-associated transcription factor (MITF) down-regulation. Furthermore, ectopic expression of the PDE4D short isoform, PDE4D2, enhanced the proliferation of cancer cells both in vitro and in vivo. Moreover, treatment of cancer cells with a unique specific PDE4D inhibitor, 26B, triggered massive cell death and growth retardation. Notably, these antineoplastic effects induced by either shRNAs or small molecule occurred preferentially in cancer cells but not in nonmalignant epithelial cells. These results suggest that although targeted by genomic homozygous microdeletions, PDE4D functions as a tumor-promoting factor and represents a unique targetable enzyme of cancer cells.

As one kind of meshless methods, the natural element method (NEM) constructs shape functions based on the Voronoi diagrams, and it has advantages of both the conventional meshless method and the finite element method. Since the nodes are independent of the integral mesh, it is more suitable for the analysis of seepage with a free surface than the finite element method. In addition, its shape functions satisfy the Kronecker δ conditions, therefore, its boundary conditions can be dealt with much easily than those of such meshless method as element-free Galerkin method (EFGM). In this paper, the NEM was used in the seepage analysis of dams. The initial free surface was assumed first in the calculations, and the location of the free surface was adjusted according to the calculation results. The examples showed that the natural element method lead to satisfactory results.

The present study was designed to investigate the phenotypic transformation and migration of adventitial fibroblasts using 5-bromo-2′-deoxyuridine (BrdU) labeling following angioplasty and to explore the correlation between adventitial cells and post-angioplasty restenosis. A vascular restenosis model was established in 23 rats by injuring the common carotid artery with a wire. BrDU was used to label the fibroblasts followed by immunohistochemistry for α-actin. Blood vessels were observed under light microscopy and scanning electron microscopy followed by image analysis. The number of BrDU-positive fibroblasts in the intima, media and adventitia of the blood vessels was determined 3, 7, 41 and 28 days after injury. The results demonstrated that at different time points, the number of BrDU-positive cells was significantly different in the intima, media and adventia (P

In the damage research before on the CT image of quasi-brittle materials such as concrete, the damage evolution is often described by the change of average CT values or image threshold segmentation method. However, the evolution of average CT values is insensitive to the damage, and the threshold value is always not only, which grimly depends on the researchers’ judgment. Because CT image is a gray image and different grayscale expresses different density distribution, it is tried in the paper to express the variety of material density with variety of grayscale of CT image. A description index of Rd from fractal theory is introduced in the paper to describe the variety of grayscale. Thereby, a damage variable is defined by Rd index, which can be used to study the developing process and evolving rule of concrete damage.

With expanding admissions in every college in our country this recent years,future education is changing forn elite to popular. Students and parents pay more and more attention in school’location.environment and other conditions, but some colleges are too far away form home for field observation, so they had to get some unintuition information about school form traditional 2D web pages ,now Virtual Campus if used with corresponding explain can work out this problem very well, and it can observe school in 360 degree comprehensivity. Virtual Campus’s design applied computer’s3D modeling method and internet informations, through computer shows the campus humanities and campus style and features, 3D Rhino is a classical “NURBS” software. It makes up surfaces rely on points and lines, and then makes up the basic grapes we need, it can establishes complex model conveniently and fastly the author select 3D Rhino as develop software make innovation study and realize in Virtual Campus. This passage introduces how to use 3D Rhino and Coogle SketchUP to make virtual school scenes, school’s 3D scene model’s making and narratives how to visit virtual campus through Google Earth ,the major content can divided into three parts. First: Study how to establish college surface 3D building’s outside scenes model ingreat detail through remote sensing satellites pictures and inside seenes shooting means get scenes datas, use 3DRhino modeling skill establish scene models.3DRhino can build complex surface effects, such as school’s sculptures\roofs\complex fences and walls’ scenes models. Second: Take Google SketchUP map measure make materials map into models to get lifelike 3D sculpture, use Google SketchUP’s truly grain or get form take photos add to model surface, Delete useless buildings details to optimization dealing with models, to prominent the features about buildings. With the advent of the Internet age , today, the computer has been deeply every family.Many famous universities such as Zhejiang University , Shanghai Jiaotong University , etc., adopting virtual reality technology to build a virtual campus .Virtual campus provides a platform ,which to help achieve the University 's resource management, environmental planning and school development , remote access, etc.In today's changing the technology will be applied to more schools with eelectronic information technology(Electronics IT) improve. In most of the campus network has been widely used, with the development of colleges and universities in our country, the improvement of the education system, more and more students have the opportunity to enter colleges and universities for further study. Many colleges and universities have to start expansion.Based on a series of teaching , accommodation and other facilities continue to increase, the effective management of the campus began to be taken seriously.Therefore, campus information management has become the most effective management.Most schools began to use the network to establish their own teaching , living, entertainment and other systems.And compared to traditional campus , virtual campus can give students a more intuitive, more effective understanding, so this technology has also vigorously developed in China. During the globalization of information, the virtual campus created the conditions for the country 's schools to the world.Online virtual campus provides many opportunities not only for Chinese students but also for foreign students to to understand each other's university , college life, and even the campus culture .Through virtual campus , schools can have a more in-depth exchanges and contacts , which not only promotes academic exchanges,but also provides favorable conditions for enhancing the competitiveness of schools and optimizing Campus. International Industrial Informatics and Computer Engineering Conference (IIICEC 2015) © 2015. The authors Published by Atlantis Press 943 Image-based modeling techniques to draw the photo images of buildings , based on a large number of environmental stresses multi-angle photos into the computer for analysis, using computer vision technology to help analyze and establish the geometry of buildings and the environment.This method does not have to establish a separate complex model to analyze automatically by a computer model , if the technology is mature , will greatly enhance the efficiency of the building modeling .In recent years, this modeling approach concern of many scholars , and is committed to improving the technology and the popularity of talk .But now computer vision technology is not mature enough , modeled by this method still requires producers to enter a lot of matching data.How to achieve between the face image matching , how to eliminate or reduce the image noise , also remains to be further studied.Image-based modeling method flow chart shown in Figure 1 . Figure 1 image modeling method 1.Virtual Campus Problems With the popularization of network technology and google , more and more universities have begun to build their own virtual campus .From a functional point of view , the virtual campus is divided into two categories: One virtual campus is mainly used to serve the campus teaching and management,and it is through the establishment of digital campus to expand the campus network functions;The other is mainly to show the campus scenery and school style, while making an inquiry and guided tours . Technically,no matter what type of virtual campuses are using virtual reality technology to show more intuitive campus buildings and scenery.But as we can see ,there are still many shortcomings in the virtual campus technology ,mainly in the interaction between the viewer and the navigation is not good enough .That there are many problems to solve and improve the process of building a virtual campus , mainly in the following aspects: 1.1 At present, virtual campus mainly adopts three-dimensional(3D) panoramic way fixed-point observation , it can not be close observation , unable to see the scenes details.In order to maximize the display of three-dimensional(3D) scenes , its preimage acquisition makes high demands . 1.2After a three-dimensional(3D) construction, virtual campus scenes are rendered into an image to be displayed. When a user browsing ,it only for fixed-point observation and not at liberty to browse ,, and it is more passive in terms of information inquiry , interaction is also poor. 1.3Realistic virtual campus scenes need to build a large geometric model, which is bound to take up a lot of storage space, the attendant problems is the browser opens the page in the network will take a long time .Therefore , a need to study the optimization method , making the model more realistic and less storage space on a balance can be achieved in improving the network transmission speed and fidelity scene coordination in hand, which in the future development of the virtual campus has very far-reaching significance. Virtual campus landscape model according to the theory of cognitive research , geographical scope of the performance of the spatial objects within the scope encompasses part of the campus .In

Nowdays, Chinese business pay more attention to build their commercial Stores Identity System. In recent years, during the process of the “ Second upgrade of corporate visual image”, academic and business circles focus on how to express the inherent brand ‘s cultural concepts and national characteristic effectively, and how to reflects psychological need of the crowd accurately. use different levels of design symbols coding rules, and get rid of some unnecessary information. Finally they will find the distinctive characteristics of the corporate brand image to enhance the brand culture and competitiveness. 1. Explore how to spread the space image with brand differences in the design methodology Based on years of practical experience, the author thinks that, in the process of national or brand characteristic symbol design, which means the encoding process of the symbol spreading, has a certain scientific laws and specific method. First in terms of methodology, we should realize clearly, in both the expression and the choice of construction materials, should be subject to the basic requirement of modern design theory and information communication, only in this way can get the accurate good symbol recognition and information arrival rate. Not split using some traditional Chinese symbols, but conformity the symbol by contemporary audience allow forms, instead of a variety of symbol of national culture, mining the most representative code combination according to scientific research, And spread these symbols according to the function different communication theory in a planned way hierarchical, is not only use ancestor or an area commonly used construction materials and technology as the carrier of the dissemination of information, but as far as possible use the most common material on the market at present, or the most easy to implement process the information. So no matter how the nationalization of the characteristic design, to meet the basic requirements of commercial space SI systemIdentify effective, moderate volume, no noise interference, convenient construction simple, easy to copy. As Mr LiZhong hair says in the book : A qualified modern designers should have three kinds of abilities-1 information understanding and application 2 constitute ability of design modelling and color 3 convey information and the ability to communicate through design. The three abilities actually represents the information of import and integration ability, design codes and performance ability, symbol of output control and message control ability. 2. Information coding level and rule of the difference brand space system According to the basic model of information communication of Shannon and Weaver., the communication process of a complete design information should abide by the following rules: From the information source(designer) get the information encoded(The design process) and then transformed into symbols or symbols groups(information)the symbol or information through certain information spreading media(channel) Interpretation by the sink(the information receiver), this process of interpretation symbols called decoding. In the links spreading channel, there is a noise interference problem, there are also symbol similar with spreading target symbolor confusing significance make the audience cannot accurately identify the symbol. So the accurate and effective coding link、control channel noise has become the key problem of this communication link which designers need to focus on. Ensure that the two links, the decoding process will fall into place, To International Industrial Informatics and Computer Engineering Conference (IIICEC 2015) © 2015. The authors Published by Atlantis Press 951 ensure the communication intention understands by the recipient. In short, the encoding process need to be aware of three major problems: The first is disseminate information for different purposes – analysis what types of information propagation, and then to determine the type of information design and code in what order which is design program, the last is the type of information needed to follow those rules or methods in the process of coding which is the design method as figure1shows. Fig 1 the symbol image Figure 2 communication link As the main brand’s space recognition, brand channel store exists in various forms、 business models and morphology,whether the brand interior stores in large shopping malls or similar kind of McDonald's outdoor shops on both sides of the street, whether it is as independent as Sinopec gas station chain form or large stores as Dazhong, Gome, as long as enterprises or brand after system of SI regulated, there are following five symbol characteristics in space system of communication channels in its business1 :1、logo and the word standard brands such as VI symbols2 performance style and modeling 3、the standard store color 4、system4 uniform material 5、The brand unique spatial aided shape。 In the multi view interpretation Symbols the designer,Symbolic interpretation’s horizons fusion shows a multiple loop structure, that is take the interpreter and the designer as the main body, the former’s attention is the interpreter perspective effect on the symbolic interpretation of behavior, the latter concern about the impact on the interpretation of the behavior of the designer perspective. As designers, we cannot control the decoding process, but can accurately interpretation symbols by careful arrangement of information and extensive research influence the information receiver, standing in the designer angle, the author believes that the above 5 big symbol feature groups can be divided into three sequentially coded information hierarchy according to their different purpose of propagation. The first is the necessary information hierarchy, including the logo and the standard word etc. the core brand visual symbols. The so-called necessary information refers to is the information need to spread, like a personal understanding another person must first know its name. Company logo and the standard word are the external performance of the enterprise internal culture, industry, and other aspects of the intrinsic characteristics of the concept, the core of the visual image or text point directly to the connotation of enterprise. No matter what stores need to first communicated to consumers is name or logo. It is known as the necessary information. Secondly the need to disseminate information hierarchy is homogeneous information hierarchy, the three main aspects of the hierarchical information including style and shape, store standard color system, unified material. The so-called homogeneous meaning is to code a dissemination of information and the same industry or the same population subdivision location nearest rival in all aspects of the requirements. This encoding is to ensure that the specification characteristics possible propagation of this industry in the practical application of SI space. After the study, different industries have different performance characteristics of the symbol, according to the features and the industry or the location of population subdivision in many industries tend to show a homogeneous rules. Take the color symbol as an example,the fast food industry such as McDonald's, KFC, pizza hut, real time, Yoshinoya etc. Volkswagen brand, its Wailimian main tone often focus on

This paper briefly introduces the clothing poster, explains the process of making this poster and simply talk about the inspiration origin of clothing designer. It points out that the corresponding poster background is produced according to related topics and images. It focuses on the poster image processing, font design, color design as well as layout design, and then orchestrate them reasonably. 1. Preparation for Poster Production 1.1 Materials collection Before producing this poster, we understand relevant contents first, and then collect relevant information and images, check out some books, search for some reference materials as comparison on the Internet and revise constantly. Designers from department of design ask about the category and inspiration of clothing and know that in most instances, clothing in each season can be divided into four series: woman series, office series, modern series and high-end series. While theme of this season is “Ocean Impression” which belongs to modern and leisure series. 1.2 Theme source Theme inspiration of this season comes from the movie “Avatar”. It draws on the ocean color system as well as the epidermal mimicry pattern of original ecological animals, and combines the heart geometric art in 1960s. In addition, it uses bionic, variation and reconstruction design techniques which makes the design modeling present a kind of relaxed and dynamic atmosphere, and highlights the modern, mysterious and cool ocean feeling of this season. 2. Poster Design Process 2.