Searching for Authoritative Documents in Knowledge-Base Communities

Knowledge-based communities are popular Web-based tools that allow members to share and seek knowledge globally. However, research on how to search effectively within such knowledge repositories is scant. In this paper we study the problem of finding authoritative documents for user queries within a knowledge-based community. Unlike prior research on the ranking function design which considers only content or hyperlink information, we leverage the social network information embedded in the rich social media, in addition to content, to design novel ranking strategies. Using the Knowledge Adoption Model as the guiding theoretical framework, we design features that gauge the two major factors affecting users’ knowledge adoption decisions: argument quality (AQ) and source credibility (SC). We design two ranking strategies that blend these two sources of evidence with the content-based relevance judgment. A preliminary study using a real world knowledge-based community showed that both AQ and SC features improved search effectiveness

Wnt1-Cre-mediated deletion of AP-2α causes multiple neural crest-related defects

AbstractThe AP-2α transcription factor is required for multiple aspects of vertebrate development and mice lacking the AP-2α gene (tcfap2a) die at birth from severe defects affecting the head and trunk. Several of the defects associated with the tcfap2a-null mutation affect neural crest cell (NCC) derivatives including the craniofacial skeleton, cranial ganglia, and heart outflow tract. Consequently, there is considerable interest in the role of AP-2α in neural crest cell function in development and evolution. In addition, the expression of the AP-2α gene is utilized as a marker for premigratory and migratory neural crest cells in many vertebrate species. Here, we have specifically addressed how the presence of AP-2α in neural crest cells affects development by creating a conditional (floxed) version of tcfap2a which has subsequently been intercrossed with mice expressing Cre recombinase under the control of Wnt1 cis-regulatory sequences. Neural crest-specific disruption of tcfap2a results in frequent perinatal lethality associated with neural tube closure defects and cleft secondary palate. A small but significant fraction of mutant mice can survive into adulthood, but have retarded craniofacial growth, abnormal middle ear development, and defects in pigmentation. The phenotypes obtained confirm that AP-2α directs important aspects of neural crest cell function. At the same time, we did not observe several neurocristopathies affecting the head and heart that might be expected based on the phenotype of the AP-2α-null mouse. These results have important implications for the evolution and function of the AP-2 gene family in both the neural crest and the vertebrate embryo

Whole Genome Association Analysis of Idiopathic Eosinophilic Enteritis in Brown Egg Layers

Idiopathic Eosinophilic Enteritis (IEE) is an intestine disease that affects absorption of nutrients and performance. Hens of a commercial breeding layer line and its two reciprocal crosses with another line were recorded for IEE related traits and genotyped for over 40,000 genetic markers across the genome. Whole genome association analysis was performed on 288 daughters from high and low incidence sire families. Single marker association analyses of IEE incidence in separate lines showed consistent significant regions on chromosomes 4 and 5 (p\u3c0.001). Simultaneous analyses of all SNPs in all 3 lines using Bayesian whole genome selection methods indicated evidence of associations on chromosomes 1, 2 and 4 for additive effects and on chromosome 5 for dominance effects. Line specific regions also appeared on chromosome Z. With further investigation, these results can be used to develop genetic markers to select against this disease and to understand its genetic basis

Chemoprevention of BBN-Induced Bladder Carcinogenesis by the Selective Estrogen Receptor Modulator Tamoxifen

AbstractBladder cancer is the fifth most frequent tumor in men and ninth in women in the United States. Due to a high likelihood of recurrence, effective chemoprevention is a significant unmet need. Estrogen receptors (ERs), primarily ERβ, are expressed in normal urothelium and urothelial carcinoma, and blocking ER function with selective ER modulators such as tamoxifen inhibits bladder cancer cell proliferation in vitro. Herein, the chemoprotective potential of tamoxifen was evaluated in female mice exposed to the bladder-specific carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Carcinogen treatment resulted in a 76% tumor incidence and increased mean bladder weights in comparison to controls. In contrast, mice receiving tamoxifen concurrent (8–20 weeks) or concurrent and subsequent (8–32 weeks) to BBN administration had no change in bladder weight and only 10% to 14% incidence of tumors. Non-muscle-invasive disease was present in animals treated with tamoxifen before (5–8 weeks) or after (20–32 weeks) BBN exposure, while incidence of muscle-invasive bladder carcinoma was reduced. ERβ was present in all mice and thus is a potential mediator of the tamoxifen chemoprotective effect. Surprisingly, ERα expression, which was detected in 74% of the mice exposed to BBN alone but not in any controlmice, was correlated with tumor incidence, indicating a possible role for this receptor in carcinogen-induced urothelial tumorigenesis. Thus, these data argue that both ERα and ERβ play a role in modulating carcinogen-induced bladder tumorigenesis. Administration of tamoxifen should be tested as a chemopreventive strategy for patients at high risk for bladder cancer recurrence

CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents

Multidrug resistance (MDR) of hepatocellular carcinoma is a serious problem. Although CD13 is a biomarker in human liver cancer stem cells, the relationship between CD13 and MDR remains uncertain. This study uses liver cancer cell model to understand the role of CD13 in enhancing the cytotoxic effect of chemotherapy agents. Cytotoxic agents can induce CD13 expression. CD13 inhibitor, bestatin, enhances the antitumor effect of cytotoxic agents. Meanwhile, CD13-targeting siRNA and neutralizing antibody can enhance the cytotoxic effect of 5-fluorouracil (5FU). CD13 overexpression increases cell survival upon cytotoxic agents treatment, while the knockdown of CD13 causes hypersensitivity of cells to cytotoxic agents treatment. Mechanistically, the inhibition of CD13 leads to the increase of cellular reactive oxygen species (ROS). BC-02 is a novel mutual prodrug (hybrid drug) of bestatin and 5FU. Notably, BC-02 can inhibit cellular activity in both parental and drug-resistant cells, accompanied with significantly increased ROS level. Moreover, the survival time of Kunming mice bearing H22 cells under BC-02 treatment is comparable to the capecitabine treatment at maximum dosage. These data implicate a therapeutic method to reverse MDR by targeting CD13, and indicate that BC-02 is a potent antitumor compound