Knowledge Reused Outlier Detection

Tremendous efforts have been invested in the unsupervised outlier detection research, which is conducted on unlabeled data set with abnormality assumptions. With abundant related labeled data available as auxiliary information, we consider transferring the knowledge from the labeled source data to facilitate the unsupervised outlier detection on target data set. To fully make use of the source knowledge, the source data and target data are put together for joint clustering and outlier detection using the source data cluster structure as a constraint. To achieve this, the categorical utility function is employed to regularize the partitions of target data to be consistent with source data labels. With an augmented matrix, the problem is completely solved by a K-means - a based method with the rigid mathematical formulation and theoretical convergence guarantee. We have used four real-world data sets and eight outlier detection methods of different kinds for extensive experiments and comparison. The results demonstrate the effectiveness and significant improvements of the proposed methods in terms of outlier detection and cluster validity metrics. Moreover, the parameter analysis is provided as a practical guide, and noisy source label analysis proves that the proposed method can handle real applications where source labels can be noisy

(5-Bromo-2-chloro­phen­yl)(4-ethoxy­phen­yl)methanone

In the title mol­ecule, C15H12BrClO2, the two benzene rings form a dihedral angle of 69.30 (3)°. In the crystal structure, weak inter­molecular C—H⋯O hydrogen bonds link mol­ecules into chains propagating along the b axis

FoxM1 Promotes Cell Proliferation, Invasion, and Stem Cell Properties in Nasopharyngeal Carcinoma

Background: The self-renewal and tumourigenicity of FoxM1 in nasopharyngeal carcinoma (NPC) remain largely unknown. In this study, we attempt to investigate the self-renewal and tumourigenicity of FoxM1 and its clinical significance in nasopharyngeal carcinoma (NPC).Methods: Several assays including cell counting Kit-8 (CCK-8) assays, colony formation, flow cytometry, immunofluorescence, tumor spheres, and mice model were used to detect the biological function of FoxM1 in NPC. The association between FoxM1 and clinical pathological features, and stem cell markers was analyzed using immunohistochemistry.Results: High expression of FoxM1 was prominently present in the T4 stages, cancer cells migrating into the stroma and vasculature. Overexpression of FoxM1 enhanced tumor proliferation, cell cycle progression, migration and stress fibers formation in vitro. In NPC tissues, FoxM1 correlated significantly with stem cells-related clinical pathological features including late clinical stage, tumor recurrence and distant metastasis. Meanwhile, FoxM1 linked closely with the expression levels of stem cell markers including Nanog, Sox2, and OCT4 in tumor samples, and also promoted the expression of these stemness-related genes in vitro. Moreover, FoxM1 conferred the self-renewal properties of cancer cells by increasing side populations (SP) cells and formed larger and more tumor spheres. Importantly, FoxM1 enhanced the ability of tumourigenicity of NPC cell lines in mice xenograft.Conclusions: We demonstrate that FoxM1 greatly induces cancer progression and cancer stem cell (CSC) features in NPC

Protective effect of Macleaya cordata isoquinoline alkaloids on lipopolysaccharide-induced liver injury in broilers

Objective This experiment aimed to explore the protective action of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata on lipopolysaccharide (LPS)-induced liver injury in broilers. Methods Total 216 healthy broilers were selected in a 21-d trial and assigned randomly to the following 3 treatments: control (CON) group, LPS group, and LPS+IA group. The CON and LPS groups were provided with a basal diet, whereas the LPS+IA group received the basal diet supplemented with 0.6 mg/kg Macleaya cordata IA. Broilers in LPS and LPS+IA groups were intraperitoneally injected with LPS (1 mg/kg body weight) at 17, 19, and 21 days of age, while those in CON group were injected with equivalent amount of saline solution. Results Results showed LPS injection caused systemic and liver inflammation in broilers, inhibited immune function, and ultimately lead to liver injury. By contrast, supplementation of IA ameliorated LPS-induced adverse change in serum parameters, boosted immunity in LPS+IA group. Furthermore, IA suppressed the elevation of hepatic inflammatory cytokines and caspases levels induced by LPS, as well as the expressions of genes related to the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Conclusion Dietary inclusion of 0.6 mg/kg Macleaya cordata IA could enhance immune function of body and inhibit liver damage via inactivating TLR4/MyD88/NF-κB signaling pathway in broilers

Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma

<p>Abstract</p> <p>Introduction</p> <p>The aim of the present study was to analyze the expression of matrix metalloproteinase 9 (<it>MMP9</it>) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including the survival of patients with NPC.</p> <p>Methods</p> <p>Using real-time PCR, we detected the mRNA expression of <it>MMP9 </it>in normal nasopharyngeal tissues and nasopharyngeal carcinoma (NPC) tissues. Using immunohistochemistry analysis, we analyzed <it>MMP9 </it>protein expression in clinicopathologically characterized 164 NPC cases (116 male and 48 female) with age ranging from 17 to 80 years (median = 48.4 years) and 32 normal nasopharyngeal tissues. Cases with greater than or equal to 6 and less than 6 of the score value of cytoplasmic <it>MMP9 </it>immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of <it>MMP9 </it>and clinical features was analyzed.</p> <p>Results</p> <p>The expression level of <it>MMP9 </it>mRNA was markedly greater in NPC tissues than that in the nasopharyngeal tissues. Immunohistochemical analysis revealed that the protein expression of <it>MMP9 </it>detected in NPC tissues was higher than that in the nasopharyngeal tissues (<it>P </it>= 0.004). In addition, high levels of <it>MMP9 </it>protein were positively correlated with the status of lymph node metastasis (N classification) (<it>P </it>= 0.002) and clinical stage (<it>P </it>< 0.001) of NPC patients. Patients with higher <it>MMP9 </it>expression had a significantly shorter overall survival time than did patients with low <it>MMP9 </it>expression. Multivariate analysis suggested that the level of <it>MMP9 </it>expression was an independent prognostic indicator (<it>P </it>= 0.008) for the survival of patients with NPC.</p> <p>Conclusion</p> <p>High level of <it>MMP9 </it>expression is a potential unfavorable prognostic factor for patients with NPC.</p

Analysis of single-cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma

BACKGROUND: Exhausted T cells and regulatory T cells (Tregs) comprise diverse subsets of tumor immunosuppressive microenvironment that play key roles in tumor progress. Understanding subset diversity in T cells is a critical question for developing cancer immunotherapy. METHODS: A total of 235 specimens from surgical resections of hepatocellular carcinoma (HCC) patients were examined for infiltration of exhausted T cell (Tex) in tumor and adjacent tissue. We conducted deep single-cell targeted immune profiling on CD3 RESULTS: We observed transitional differentiation of exhausted CD8 CONCLUSIONS: T cell exhaustion is a progressive process, and the gene-expression profiling displayed T cell exhaustion and anergy are different. Accordingly, it is possible that functional exhaustion is caused by the combination effects of passive defects and overactivation in stress response. The results help to understand the dynamic framework of T cells function in cancer which is important for designing rational cancer immunotherapies

Elevated expression of CDK4 in lung cancer

<p/> <p>Background</p> <p>The aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 (<it>CDK4</it>) in lung cancer and its correlation with clinicopathologic features. Furthermore, the involvement of <it>CDK4</it>-mediated cell cycle progression and its molecular basis were investigated in the pathogenesis of lung cancer.</p> <p>Methods</p> <p>Using immunohistochemistry analysis, we analyzed <it>CDK4 </it>protein expression in 89 clinicopathologically characterized lung cancer patients (59 males and 30 females) with ages ranging from 36 to 78 years and compared them to 23 normal lung tissues. Cases with cytoplasmic and nuclear <it>CDK4 </it>immunostaining score values greater than or equal to 7 were regarded as high expression while scores less than 7 were considered low expression. The correlation between the expression level of <it>CDK4 </it>and clinical features was analyzed. Furthermore, we used lentiviral-mediated shRNA to suppress the expression of CDK4 and investigate its function and molecular mechanism for mediating cell cycle progression.</p> <p>Results</p> <p>The expression level of <it>CDK4 </it>protein was significantly increased in lung cancer tissues compared to normal tissues (<it>P </it>< 0.001). In addition, high levels of <it>CDK4 </it>protein were positively correlated with the status of pathology classification (<it>P </it>= 0.047), lymph node metastasis (<it>P </it>= 0.007), and clinical stage (<it>P </it>= 0.004) of lung cancer patients. Patients with higher <it>CDK4 </it>expression had a markedly shorter overall survival time than patients with low <it>CDK4 </it>expression. Multivariate analysis suggested the level of <it>CDK4 </it>expression was an independent prognostic indicator (<it>P </it>< 0.001) for the survival of patients with lung cancer. Use of lentiviral-mediated shRNA to inhibit the expression of <it>CDK4 </it>in lung cancer cell line A549 not only inhibited cell cycle progression, but also dramatically suppressed cell proliferation, colony formation, and migration. Furthermore, suppressing <it>CDK4 </it>expression also significantly elevated the expression of cell cycle regulator <it>p21</it></p> <p>Conclusion</p> <p>Overexpressed <it>CDK4 </it>is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression of <it>p21 </it>in lung cancer</p

Inhibition of P-Glycoprotein by HIV Protease Inhibitors Increases Intracellular Accumulation of Berberine in Murine and Human Macrophages

Background HIV protease inhibitor (PI)-induced inflammatory response in macrophages is a major risk factor for cardiovascular diseases. We have previously reported that berberine (BBR), a traditional herbal medicine, prevents HIV PI-induced inflammatory response through inhibiting endoplasmic reticulum (ER) stress in macrophages. We also found that HIV PIs significantly increased the intracellular concentrations of BBR in macrophages. However, the underlying mechanisms of HIV PI-induced BBR accumulation are unknown. This study examined the role of P-glycoprotein (P-gp) in HIV PI-mediated accumulation of BBR in macrophages. Methodology and Principal Findings Cultured mouse RAW264.7 macrophages, human THP-1-derived macrophages, Wild type MDCK (MDCK/WT) and human P-gp transfected (MDCK/P-gp) cells were used in this study. The intracellular concentration of BBR was determined by HPLC. The activity of P-gp was assessed by measuring digoxin and rhodamine 123 (Rh123) efflux. The interaction between P-gp and BBR or HIV PIs was predicated by Glide docking using Schrodinger program. The results indicate that P-gp contributed to the efflux of BBR in macrophages. HIV PIs significantly increased BBR concentrations in macrophages; however, BBR did not alter cellular HIV PI concentrations. Although HIV PIs did not affect P-gp expression, P-gp transport activities were significantly inhibited in HIV PI-treated macrophages. Furthermore, the molecular docking study suggests that both HIV PIs and BBR fit the binding pocket of P-gp, and HIV PIs may compete with BBR to bind P-gp. Conclusion and Significance HIV PIs increase the concentration of BBR by modulating the transport activity of P-gp in macrophages. Understanding the cellular mechanisms of potential drug-drug interactions is critical prior to applying successful combinational therapy in the clinic

Concept for a Future Super Proton-Proton Collider

Following the discovery of the Higgs boson at LHC, new large colliders are being studied by the international high-energy community to explore Higgs physics in detail and new physics beyond the Standard Model. In China, a two-stage circular collider project CEPC-SPPC is proposed, with the first stage CEPC (Circular Electron Positron Collier, a so-called Higgs factory) focused on Higgs physics, and the second stage SPPC (Super Proton-Proton Collider) focused on new physics beyond the Standard Model. This paper discusses this second stage.Comment: 34 pages, 8 figures, 5 table