COST-SENSITIVE STRUCTURED PERCEPTRON INCORPORATING CATEGORY HIERARCHY FOR NAMED ENTITY RECOGNITION

Named Entity Recognition (NER) is a fundamental natural language processing task for the identifi cation and classifi cation of expressions into predefi ned categories, such as person and organization. Existing NER systems usually target about 10 categories and do not incorporate analysis of category relations. However, categories often belong naturally to some predefi ned hierarchy. In such cases, the distance between categories in the hierarchy becomes a rich source of information that can be exploited. This is intuitively useful particularly when the categories are numerous. On that account, this paper proposes an NER approach that can leverage category hierarchy information by introducing, in the structured perceptron framework, a cost function more strongly penalizing category predictions that are more distant from the correct category in the hierarchy. Experimental results on the GENIA biomedical text corpus indicate the effectiveness of the proposed approach as compared with the case where no cost function is utilized. In addition, the proposed approach demonstrates the superior performance over a representative work using multi-class support vector machines on the same corpus. A possible direction to further improve the proposed approach is to investigate more elaborate cost functions than a simple additive cost adopted in this work.

Cost-sensitive structured perceptron incorporating category hierarchy for named entity recognition

Named Entity Recognition (NER) is a fundamental natural language processing task for the identification and classification of expressions into predefined categories, such as person and organization.Existing NER systems usually target about 10 categories and do not incorporate analysis of category relations.However, categories often belong naturally to some predefined hierarchy.In such cases, the distance between categories in the hierarchy becomes a rich source of information that can be exploited.This is intuitively useful particularly when the categories are numerous.On that account, this paper proposes an NER approach that can leverage category hierarchy information by introducing, in the structured perceptron framework, a cost function more strongly penalizing category predictions that are more distant from the correct category in the hierarchy.Experimental results on the GENIA biomedical text corpus indicate the effectiveness of the proposed approach as compared with the case where no cost function is utilized. In addition, the proposed approach demonstrates the superior performance over a representative work using multi-class support vector machines on the same corpus.A possible direction to further improve the proposed approach is to investigate more elaborate cost functions than a simple additive cost adopted in this work

Hydrophobic Amino Acid Tryptophan Shows Promise as a Potential Absorption Enhancer for Oral Delivery of Biopharmaceuticals

Cell-penetrating peptides (CPPs) have great potential to efficiently deliver drug cargos across cell membranes without cytotoxicity. Cationic arginine and hydrophobic tryptophan have been reported to be key component amino acids for cellular internalization of CPPs. We recently found that l-arginine could increase the oral delivery of insulin in its single amino acid form. Therefore, in the present study, we evaluated the ability of another key amino acid, tryptophan, to enhance the intestinal absorption of biopharmaceuticals. We demonstrated that co-administration with l-tryptophan significantly facilitated the oral and intestinal absorption of the peptide drug insulin administered to rats. Furthermore, l-tryptophan exhibited the ability to greatly enhance the intestinal absorption of other peptide drugs such as glucagon-like peptide-1 (GLP-1), its analog Exendin-4 and macromolecular hydrophilic dextrans with molecular weights ranging from 4000 to 70,000 g/mol. However, no intermolecular interaction between insulin and l-tryptophan was observed and no toxic alterations to epithelial cellular integrity—such as changes to cell membranes, cell viability, or paracellular tight junctions—were found. This suggests that yet to be discovered inherent biological mechanisms are involved in the stimulation of insulin absorption by co-administration with l-tryptophan. These results are the first to demonstrate the significant potential of using the single amino acid l-tryptophan as an effective and versatile bioavailability enhancer for the oral delivery of biopharmaceuticals

In Vivo Efficacies and Pharmacokinetics of DX-619, a Novel Des-Fluoro(6) Quinolone, against Streptococcus pneumoniae in a Mouse Lung Infection Model

DX-619 is a novel des-fluoro(6) quinolone with potent activity against gram-positive pathogens. The in vivo activity of DX-619 against Streptococcus pneumoniae was compared with those of fluoro(6) quinolones, sitafloxacin, and ciprofloxacin in a mouse model. Two strains of S. pneumoniae were used: a penicillin-sensitive S. pneumoniae (PSSP) strain and a penicillin-resistant S. pneumoniae (PRSP) strain. Furthermore, these strains showed intermediate susceptibilities to ciprofloxacin. In murine lung infections caused by PSSP, the 50% effective doses (ED(50)s) of DX-619, sitafloxacin, and ciprofloxacin were 9.15, 11.1, and 127.6 mg/kg of body weight, respectively. Against PRSP-mediated pneumonia in mice, the ED(50)s of DX-619, sitafloxacin, and ciprofloxacin were 0.69, 4.84, and 38.75 mg/kg, respectively. The mean ± standard error of the mean viable bacterial counts in murine lungs infected with PSSP and treated with DX-619, sitafloxacin, ciprofloxacin (10 mg/kg twice daily), and saline (twice daily) were 1.75 ± 0.06, 1.92 ± 0.23, 6.48 ± 0.28, and 7.57 ± 0.13 log(10) CFU/ml, respectively. Furthermore, the numbers of viable bacteria in lungs infected with PRSP and treated with the three agents and not treated (control) were 1.73 ± 0.04, 2.28 ± 0.17, 4.61 ± 0.59, and 5.54 ± 0.72 log(10) CFU/ml, respectively. DX-619 and sitafloxacin significantly decreased the numbers of viable bacteria in the lungs compared to the numbers in the lungs of ciprofloxacin-treated and untreated mice. The pharmacokinetic parameter of the area under the concentration-time curve (AUC)/MIC ratio in the lungs for DX-619, sitafloxacin, and ciprofloxacin were 171.0, 21.92, and 1.22, respectively. The AUC/MIC ratio in the lungs was significantly higher for DX-619 than for sitafloxacin and ciprofloxacin. Our results suggest that DX-619 and sitafloxacin are potent against both PSSP and PRSP in our mouse pneumonia model

A Case of Bilateral Decidualized Endometriomas during Pregnancy: Radiologic-pathologic Correlation

Clinical differentiation between decidualized endometrioma and malignant transformation still poses difficulties as both are intracystic vascularized excrescences of an endometrial cyst and exhibit similar characteristics on color-flow Doppler sonography. This is a characteristic sonographic finding associated with ovarian cancer, but MRI can provide further information about mural excrescences that can aid in their differential diagnosis; for example, the signal of decidualized endometriomas is isointense with the placenta within the uterus on all sequences and the apparent diffusion coefficient is higher than that of malignant mural nodules. Thus, MRI should be an aid in deciding whether to intervene during pregnancy. However, considering that it is not yet possible to clearly differentiate decidualized endometriomas from ovarian cancer, surgery or watchful observation may still be needed to exclude the possibility of malignancy

A Case of Bilateral Decidualized Endometriomas during Pregnancy: Radiologic-pathologic Correlation

Clinical differentiation between decidualized endometrioma and malignant transformation still poses difficulties as both are intracystic vascularized excrescences of an endometrial cyst and exhibit similar characteristics on color-flow Doppler sonography. This is a characteristic sonographic finding associated with ovarian cancer, but MRI can provide further information about mural excrescences that can aid in their differential diagnosis; for example, the signal of decidualized endometriomas is isointense with the placenta within the uterus on all sequences and the apparent diffusion coefficient is higher than that of malignant mural nodules. Thus, MRI should be an aid in deciding whether to intervene during pregnancy. However, considering that it is not yet possible to clearly differentiate decidualized endometriomas from ovarian cancer, surgery or watchful observation may still be needed to exclude the possibility of malignancy

Azithromycin Inhibits MUC5AC Production Induced by the Pseudomonas aeruginosa Autoinducer N-(3-Oxododecanoyl) Homoserine Lactone in NCI-H292 Cells

The features of chronic airway diseases, including chronic bronchitis, cystic fibrosis, bronchiectasis, and diffuse panbronchiolitis, include chronic bacterial infection and airway obstruction by mucus. Pseudomonas aeruginosa is one of the most common pathogens in chronic lung infection, and quorum-sensing systems contribute to the pathogenesis of this disease. The quorum-sensing signal molecule [N-(3-oxododecanoyl) homoserine lactone (3O-C(12)-HSL)] not only regulates bacterial virulence but also is associated with the immune response. In this study, we investigated whether 3O-C(12)-HSL could stimulate the production of a major mucin core protein, MUC5AC. The effect of a macrolide on MUC5AC production was also studied. 3O-C(12)-HSL induced NCI-H292 cells to express MUC5AC at both the mRNA and the protein levels in time- and dose-dependent manners. A 15-membered macrolide, azithromycin, inhibited MUC5AC production that was activated by 3O-C(12)-HSL. 3O-C(12)-HSL induced extracellular signal-regulated kinase (ERK) 1/2 and I-κB phosphorylation in cells, and this induction was suppressed by azithromycin. 3O-C(12)-HSL-induced MUC5AC production was blocked by the ERK pathway inhibitor PD98059. Our findings suggest that the P. aeruginosa autoinducer 3O-C(12)-HSL contributes to excessive mucin production in chronic bacterial infection. Azithromycin seems to reduce this mucin production by interfering with intracellular signal transduction