The Acquisition Of Lexical Knowledge From The Web For Aspects Of Semantic Interpretation

This work investigates the effective acquisition of lexical knowledge from the Web to perform semantic interpretation. The Web provides an unprecedented amount of natural language from which to gain knowledge useful for semantic interpretation. The knowledge acquired is described as common sense knowledge, information one uses in his or her daily life to understand language and perception. Novel approaches are presented for both the acquisition of this knowledge and use of the knowledge in semantic interpretation algorithms. The goal is to increase accuracy over other automatic semantic interpretation systems, and in turn enable stronger real world applications such as machine translation, advanced Web search, sentiment analysis, and question answering. The major contributions of this dissertation consist of two methods of acquiring lexical knowledge from the Web, namely a database of common sense knowledge and Web selectors. The first method is a framework for acquiring a database of concept relationships. To acquire this knowledge, relationships between nouns are found on the Web and analyzed over WordNet using information-theory, producing information about concepts rather than ambiguous words. For the second contribution, words called Web selectors are retrieved which take the place of an instance of a target word in its local context. The selectors serve for the system to learn the types of concepts that the sense of a target word should be similar. Web selectors are acquired dynamically as part of a semantic interpretation algorithm, while the relationships in the database are useful to iii stand-alone programs. A final contribution of this dissertation concerns a novel semantic similarity measure and an evaluation of similarity and relatedness measures on tasks of concept similarity. Such tasks are useful when applying acquired knowledge to semantic interpretation. Applications to word sense disambiguation, an aspect of semantic interpretation, are used to evaluate the contributions. Disambiguation systems which utilize semantically annotated training data are considered supervised. The algorithms of this dissertation are considered minimallysupervised; they do not require training data created by humans, though they may use humancreated data sources. In the case of evaluating a database of common sense knowledge, integrating the knowledge into an existing minimally-supervised disambiguation system significantly improved results – a 20.5% error reduction. Similarly, the Web selectors disambiguation system, which acquires knowledge directly as part of the algorithm, achieved results comparable with top minimally-supervised systems, an F-score of 80.2% on a standard noun disambiguation task. This work enables the study of many subsequent related tasks for improving semantic interpretation and its application to real-world technologies. Other aspects of semantic interpretation, such as semantic role labeling could utilize the same methods presented here for word sense disambiguation. As the Web continues to grow, the capabilities of the systems in this dissertation are expected to increase. Although the Web selectors system achieves great results, a study in this dissertation shows likely improvements from acquiring more data. Furthermore, the methods for acquiring a database of common sense knowledge could be applied in a more exhaustive fashion for other types of common sense knowledge. Finally, perhaps the greatest benefits from this work will come from the enabling of real world technologies that utilize semantic interpretation

The molecular genetic analysis of the expanding pachyonychia congenita case collection

BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma and nail dystrophy, often accompanied by oral leucokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16 or KRT17. OBJECTIVES: To identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry during the last few years. METHODS: Genomic DNA isolated from saliva or peripheral blood leucocytes was amplified using primers specific for the PC-associated keratin genes and polymerase chain reaction products were directly sequenced. RESULTS: Mutations were identified in 84 families in the PC-associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105. CONCLUSIONS: By identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17, this study has confirmed, at the molecular level, the clinical diagnosis of PC in these families

Finding the glass half full? Optimism is protective of 10-year incident CHD in a population-based study: The Canadian Nova Scotia Health Survey

While some convenience studies have found that optimism is protective for the risk of incident coronary heart disease (CHD) events, others have not. Optimism is separate from, but related to positive affect. We examined whether optimism was associated with a lower long-term risk of coronary heart disease (CHD) events in a large, population-based sample, independent of positive affect with 10 years follow-up after adjusting for positive affect

Determination of a lower bound on Earth’s climate sensitivity

Transient and equilibrium sensitivity of Earth's climate has been calculated using global temperature, forcing and heating rate data for the period 1970–2010. We have assumed increased long-wave radiative forcing in the period due to the increase of the long-lived greenhouse gases. By assuming the change in aerosol forcing in the period to be zero, we calculate what we consider to be lower bounds to these sensitivities, as the magnitude of the negative aerosol forcing is unlikely to have diminished in this period. The radiation imbalance necessary to calculate equilibrium sensitivity is estimated from the rate of ocean heat accumulation as 0.37±0.03W m^−2 (all uncertainty estimates are 1−σ). With these data, we obtain best estimates for transient climate sensitivity 0.39±0.07K (W m^−2)^−1 and equilibrium climate sensitivity 0.54±0.14K (W m^−2)^−1, equivalent to 1.5±0.3 and 2.0±0.5K (3.7W m^−2)^−1, respectively. The latter quantity is equal to the lower bound of the ‘likely’ range for this quantity given by the 2007 IPCC Assessment Report. The uncertainty attached to the lower-bound equilibrium sensitivity permits us to state, within the assumptions of this analysis, that the equilibrium sensitivity is greater than 0.31K (W m^−2)^−1, equivalent to 1.16K(3.7W m^−2)^−1, at the 95% confidence level

Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119

AbstractGPR119 is a Gαs-coupled lipid-sensor in the gut, where it mediates release of incretin hormones from the enteroendocrine cells and in pancreatic α-cells, where it releases insulin. Naturally occurring lipids such as monoacylglycerols (MAGs) and N-acylethanolamines (NAEs), like oleoylethanolamide (OEA), activate GPR119, and multiple synthetic ligands have been described. Here, we extend the GPR119 signaling profile to Gαq and Gαi in addition to β-arrestin recruitment and the downstream transcription factors CRE (cAMP response element), SRE (serum response element) and NFAT (nuclear factor of activated T cells). The endogenous OEA and the synthetic AR231453 were full agonists in all pathways except for NFAT, where no ligand-modulation was observed. The potency of AR231453 varied <16-fold (EC50 from 6 to 95nM) across the different signaling pathways, whereas that of OEA varied >175-fold (from 85nM to 15μM) indicating a biased signaling for OEA. The degree of constitutive activity was 1–10%, 10–30% and 30–70% of OEA-induced Emax in Gαi, Gαq and Gαs-driven pathways, respectively. This coincided with the lowest and highest OEA potency observed in Gαi and Gαs-driven pathways, respectively. Incubation for 2h with the 2-MAG-lipase inhibitor JZL84 doubled the constitutive activity, indicating that endogenous lipids contribute to the apparent constitutive activity. Finally, besides being an agonist, AR231453 acted as a positive allosteric modulator of OEA and increased its potency by 54-fold at 100nM AR231453. Our studies uncovering broad and biased signaling, masked constitutive activity by endogenous MAGs, and ago-allosteric properties of synthetic ligands may explain why many GPR119 drug-discovery programs have failed so far

Comprehensive Analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 Loci and Squamous Cell Cervical Cancer Risk

Variation in human major histocompatibility genes may influence the risk of squamous cell cervical cancer (SCC) by altering the efficiency of the T-cell–mediated immune response to human papillomavirus (HPV) antigens. We used high-resolution methods to genotype human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1 and DQB1) loci in 544 women with SCC and 542 controls. Recognizing that HLA molecules are codominantly expressed, we focused on co-occurring alleles. Among 137 allele combinations present at >5% in the case or control groups, 36 were significantly associated with SCC risk. All but one of the 30 combinations that increased risk included DQB1*0301, and 23 included subsets of A*0201-B*4402-Cw*0501-DRB1*0401-DQB1*0301. Another combination, B*4402-DRB1*1101-DQB1*0301, conferred a strong risk of SCC (odds ratio, 10.0; 95% confidence interval, 3.0–33.3). Among the six combinations that conferred a decreased risk of SCC, four included Cw*0701 or DQB1*02. Most multilocus results were similar for SCC that contained HPV16; a notable exception was A*0101-B*0801-Cw*0701-DRB1*0301-DQB1*0201 and its subsets, which were associated with HPV16-positive SCC (odds ratio, 0.5; 95% confidence interval, 0.3–0.9). The main multilocus associations were replicated in studies of cervical adenocarcinoma and vulvar cancer. These data confirm that T helper and cytotoxic T-cell responses are both important cofactors with HPV in cervical cancer etiology and indicate that co-occurring HLA alleles across loci seem to be more important than individual alleles. Thus, certain co-occurring alleles may be markers of disease risk that have clinical value as biomarkers for targeted screening or development of new therapies

Critical behavior of a fluid in a disordered porous matrix: An Ornstein-Zernike approach

Using a liquid-state approach based on Ornstein-Zernike equations, we study the behavior of a fluid inside a porous disordered matrix near the liquid-gas critical point.The results obtained within various standard approximation schemes such as lowest-order $\gamma$-ordering and the mean-spherical approximation suggest that the critical behavior is closely related to that of the random-field Ising model (RFIM).Comment: 10 pages, revtex, to appear in Physical Review Letter

Human Vascular Tissue Models Formed from Human Induced Pluripotent Stem Cell Derived Endothelial Cells

Here we describe a strategy to model blood vessel development using a well-defined induced pluripotent stem cell-derived endothelial cell type (iPSC-EC) cultured within engineered platforms that mimic the 3D microenvironment. The iPSC-ECs used here were first characterized by expression of endothelial markers and functional properties that included VEGF responsiveness, TNF-α-induced upregulation of cell adhesion molecules (MCAM/CD146; ICAM1/CD54), thrombin-dependent barrier function, shear stress-induced alignment, and 2D and 3D capillary-like network formation in Matrigel. The iPSC-ECs also formed 3D vascular networks in a variety of engineering contexts, yielded perfusable, interconnected lumen when co-cultured with primary human fibroblasts, and aligned with flow in microfluidics devices. iPSC-EC function during tubule network formation, barrier formation, and sprouting was consistent with that of primary ECs, and the results suggest a VEGF-independent mechanism for sprouting, which is relevant to therapeutic anti-angiogenesis strategies. Our combined results demonstrate the feasibility of using a well-defined, stable source of iPSC-ECs to model blood vessel formation within a variety of contexts using standard in vitro formats.National Institutes of Health (U.S.) (NIH 1UH2 TR000506-01)National Institutes of Health (U.S.) (3UH2 TR000506-02S1)National Institutes of Health (U.S.) (T32 HL007936-12)National Institutes of Health (U.S.) (RO1 HL093282)National Institutes of Health (U.S.) (R21 EB016381-01

Electron heating at Saturn's bow shock

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94695/1/jgra21551.pd