Regulation of two P450 isoforms: CYP2D6 and CYP4F11

Cytochromes P450 catalyze a monooxygenase reaction in which molecular oxygen is split and one oxygen atom is incorporated into the substrate. As a whole, P450 researchers have focused most of their attention on substrate metabolism and relatively little on how these enzymes are regulated. This study will focus on the regulation of two P450 isoforms known as, CYP2D6 and CYP4F11. ^ The human CYP2D gene locus contains two pseudogenes and one functional gene known as CYP2D6. This locus is highly polymorphic and produces several alternatively spliced transcripts from the pseudogene CYP2D7. My objective was to understand the role of SV5-in (splice variant 5), one of several alternative splice variants transcribed from the CYP2D7 pseudogene. My results indicate that SV5-in mRNA causes an increase in CYP2D6 protein levels and suggest that there is a role for SV5-in in regulation of CYP2D6 expression. ^ Second, CYP4F11 is a recently discovered and uncharacterized isoform, derived from the CYP4F subfamily. It metabolizes several clinically relevant drugs (i.e.—erythromycin and benzphetamine) and some endogenous inflammatory mediators (i.e.—LTB4). After evaluation of microarray data, I observed an increase in CYP4F11 mRNA levels from wild-type HCT116 cells compared to p53-null cells. Our objectives were to explore and understand this connection between p53 and CYP4F11. Microarray data were confirmed by Q-PCR, after which this effect was again observed at the protein level via Western blot and again at the promoter level via luciferase assay and chromatin immunoprecipitation. Our results indicate that p53 protein regulates expression of CYP4F11 mRNA and protein through CYP4F11 promoter binding (note that p53 binding to CYP4F11 DNA was not shown to be direct). These results signify a whole new level of regulation of drug metabolizing enzymes by p53. ^ An understanding of CYP4F11 regulation by p53 could help us understand another pathway leading to apoptosis or cell growth arrest. This can aid future drug studies and discover new drug metabolism pathways under the control of a tumor suppressor protein. An understanding of the CYP2D6 regulation pathway could illuminate the role of non-coding RNAs in the P450 field and potentially explain several inter-individual drug response variations observed in clinical medicine that are not yet completely explained by genotyping analysis. ^

The epidemiology of left ventricular outflow tract obstruction defects in Texas, 2002-2008: An update and assessment of effect heterogeneity

Left ventricular outflow tract (LVOT) defects are an important group of congenital heart defects (CHDs) because of their associated mortality and long-term complications. LVOT defects include aortic valve stenosis (AVS), coarctation of aorta (CoA), and hypoplastic left heart syndrome (HLHS). Despite their clinical significance, their etiology is not completely understood. Even though the individual component phenotypes (AVS, CoA, and HLHS) may have different etiologies, they are often "lumped" together in epidemiological studies. Though "lumping" of component phenotypes may improve the power to detect associations, it may also lead to ambiguous findings if these defects are etiologically distinct. This is due to potential for effect heterogeneity across component phenotypes. ^ This study had two aims: (1) to identify the association between various risk factors and both the component (i.e., split) and composite (i.e., lumped) LVOT phenotypes, and (2) to assess the effect heterogeneity of risk factors across component phenotypes of LVOT defects. ^ This study was a secondary data analysis. Primary data were obtained from the Texas Birth Defect Registry (TBDR). TBDR uses an active surveillance method to ascertain birth defects in Texas. All cases of non complex LVOT defects which met our inclusion criteria during the period of 2002–2008 were included in the study. The comparison groups included all unaffected live births for the same period (2002–2008). Data from vital statistics were used to evaluate associations. Statistical associations between selected risk factors and LVOT defects was determined by calculating crude and adjusted prevalence ratio using Poisson regression analysis. Effect heterogeneity was evaluated using polytomous logistic regression. ^ There were a total of 2,353 cases of LVOT defects among 2,730,035 live births during the study period. There were a total of 1,311 definite cases of non-complex LVOT defects for analysis after excluding "complex" cardiac cases and cases associated with syndromes (n=168). Among infant characteristics, males were at a significantly higher risk of developing LVOT defects compared to females. Among maternal characteristics, significant associations were seen with maternal age > 40 years (compared to maternal age 20–24 years) and maternal residence in Texas-Mexico border (compared to non-border residence). Among birth characteristics, significant associations were seen with preterm birth and small for gestation age LVOT defects. ^ When evaluating effect heterogeneity, the following variables had significantly different effects among the component LVOT defect phenotypes: infant sex, plurality, maternal age, maternal race/ethnicity, and Texas-Mexico border residence. ^ This study found significant associations between various demographic factors and LVOT defects. While many findings from this study were consistent with results from previous studies, we also identified new factors associated with LVOT defects. Additionally, this study was the first to assess effect heterogeneity across LVOT defect component phenotypes. These findings contribute to a growing body of literature on characteristics associated with LVOT defects. ^

Grain-size distribution, carbon and calcium carbonate at DSDP Leg 63 Holes

Sand-silt-clay distribution was determined at Scripps on samples collected at the time the cores were split and described. The sediment classification used here is that of Shepard (1954); sand, silt, and clay boundaries are determined on the basis of the Wentworth (1922) scale. Thus the sand, silt, and clay fractions are composed of particles whose diameters range from 2000 to 62.5 µm, 62.5 to 3.91 µm, and less than 3.91 µm, respectively. This classification is applied regardless of sediment type and origin.

Grain-size, carbon and calcium carbonate at DSDP Leg 77 Holes

Sand-silt-clay distribution was determined on 10-cm**3 sediment samples collected at the time the cores were split and described.

Grain-size, carbona and calcium carbonate at DSDP Leg 58 Holes

Sand-silt-clay distribution was determined on 10-cm**3 sediment samples collected at the time the cores were split and described. The sediment classification used here is that of Shepard (1954), with the sand, silt, and clay boundaries based on the Wentworth (1922) scale. Thus the sand, silt, and clay fractions are composed of particles whose diameters are 2000 to 62.5 µm, 62.5 to 3.91 µm, and less than 3.91 µm, respectively. This classification is applied without regard to sediment type and origin; therefore, the sediment names used in this table may differ from those used elsewhere in this volume; e.g., a silt composed of nannofossils may be called a nannofossil ooze in a site chapter.

Grain-size and carbon/carbonate analyses at DSDP Site 61-462

Sand-silt-clay distribution was determined on 10-cm**3 sediment samples collected at the time the cores were split and described. The sediment classification used here is that of Shepard (1954), with the sand, silt, and clay boundaries based on the Wentworth (1922) scale. Thus, the sand, silt, and clay fractions are composed of particles whose diameters range from 2000 to 62.5 µm, 62.5 to 3.91 µm, and less than 3.91 µm, respectively. This classification is applied regardless of sediment type and origin; therefore, the sediment names used in this table may differ from those used elsewhere in this volume, e.g., a silt composed of nannofossils in this table may be called a nannofossil ooze in a site-summary chapter.

OntoTag - A Linguistic and Ontological Annotation Model Suitable for the Semantic Web

OntoTag - A Linguistic and Ontological Annotation Model Suitable for the Semantic Web 1. INTRODUCTION. LINGUISTIC TOOLS AND ANNOTATIONS: THEIR LIGHTS AND SHADOWS Computational Linguistics is already a consolidated research area. It builds upon the results of other two major ones, namely Linguistics and Computer Science and Engineering, and it aims at developing computational models of human language (or natural language, as it is termed in this area). Possibly, its most well-known applications are the different tools developed so far for processing human language, such as machine translation systems and speech recognizers or dictation programs. These tools for processing human language are commonly referred to as linguistic tools. Apart from the examples mentioned above, there are also other types of linguistic tools that perhaps are not so well-known, but on which most of the other applications of Computational Linguistics are built. These other types of linguistic tools comprise POS taggers, natural language parsers and semantic taggers, amongst others. All of them can be termed linguistic annotation tools. Linguistic annotation tools are important assets. In fact, POS and semantic taggers (and, to a lesser extent, also natural language parsers) have become critical resources for the computer applications that process natural language. Hence, any computer application that has to analyse a text automatically and ‘intelligently’ will include at least a module for POS tagging. The more an application needs to ‘understand’ the meaning of the text it processes, the more linguistic tools and/or modules it will incorporate and integrate. However, linguistic annotation tools have still some limitations, which can be summarised as follows: 1. Normally, they perform annotations only at a certain linguistic level (that is, Morphology, Syntax, Semantics, etc.). 2. They usually introduce a certain rate of errors and ambiguities when tagging. This error rate ranges from 10 percent up to 50 percent of the units annotated for unrestricted, general texts. 3. Their annotations are most frequently formulated in terms of an annotation schema designed and implemented ad hoc. A priori, it seems that the interoperation and the integration of several linguistic tools into an appropriate software architecture could most likely solve the limitations stated in (1). Besides, integrating several linguistic annotation tools and making them interoperate could also minimise the limitation stated in (2). Nevertheless, in the latter case, all these tools should produce annotations for a common level, which would have to be combined in order to correct their corresponding errors and inaccuracies. Yet, the limitation stated in (3) prevents both types of integration and interoperation from being easily achieved. In addition, most high-level annotation tools rely on other lower-level annotation tools and their outputs to generate their own ones. For example, sense-tagging tools (operating at the semantic level) often use POS taggers (operating at a lower level, i.e., the morphosyntactic) to identify the grammatical category of the word or lexical unit they are annotating. Accordingly, if a faulty or inaccurate low-level annotation tool is to be used by other higher-level one in its process, the errors and inaccuracies of the former should be minimised in advance. Otherwise, these errors and inaccuracies would be transferred to (and even magnified in) the annotations of the high-level annotation tool. Therefore, it would be quite useful to find a way to (i) correct or, at least, reduce the errors and the inaccuracies of lower-level linguistic tools; (ii) unify the annotation schemas of different linguistic annotation tools or, more generally speaking, make these tools (as well as their annotations) interoperate. Clearly, solving (i) and (ii) should ease the automatic annotation of web pages by means of linguistic tools, and their transformation into Semantic Web pages (Berners-Lee, Hendler and Lassila, 2001). Yet, as stated above, (ii) is a type of interoperability problem. There again, ontologies (Gruber, 1993; Borst, 1997) have been successfully applied thus far to solve several interoperability problems. Hence, ontologies should help solve also the problems and limitations of linguistic annotation tools aforementioned. Thus, to summarise, the main aim of the present work was to combine somehow these separated approaches, mechanisms and tools for annotation from Linguistics and Ontological Engineering (and the Semantic Web) in a sort of hybrid (linguistic and ontological) annotation model, suitable for both areas. This hybrid (semantic) annotation model should (a) benefit from the advances, models, techniques, mechanisms and tools of these two areas; (b) minimise (and even solve, when possible) some of the problems found in each of them; and (c) be suitable for the Semantic Web. The concrete goals that helped attain this aim are presented in the following section. 2. GOALS OF THE PRESENT WORK As mentioned above, the main goal of this work was to specify a hybrid (that is, linguistically-motivated and ontology-based) model of annotation suitable for the Semantic Web (i.e. it had to produce a semantic annotation of web page contents). This entailed that the tags included in the annotations of the model had to (1) represent linguistic concepts (or linguistic categories, as they are termed in ISO/DCR (2008)), in order for this model to be linguistically-motivated; (2) be ontological terms (i.e., use an ontological vocabulary), in order for the model to be ontology-based; and (3) be structured (linked) as a collection of ontology-based triples, as in the usual Semantic Web languages (namely RDF(S) and OWL), in order for the model to be considered suitable for the Semantic Web. Besides, to be useful for the Semantic Web, this model should provide a way to automate the annotation of web pages. As for the present work, this requirement involved reusing the linguistic annotation tools purchased by the OEG research group (http://www.oeg-upm.net), but solving beforehand (or, at least, minimising) some of their limitations. Therefore, this model had to minimise these limitations by means of the integration of several linguistic annotation tools into a common architecture. Since this integration required the interoperation of tools and their annotations, ontologies were proposed as the main technological component to make them effectively interoperate. From the very beginning, it seemed that the formalisation of the elements and the knowledge underlying linguistic annotations within an appropriate set of ontologies would be a great step forward towards the formulation of such a model (henceforth referred to as OntoTag). Obviously, first, to combine the results of the linguistic annotation tools that operated at the same level, their annotation schemas had to be unified (or, preferably, standardised) in advance. This entailed the unification (id. standardisation) of their tags (both their representation and their meaning), and their format or syntax. Second, to merge the results of the linguistic annotation tools operating at different levels, their respective annotation schemas had to be (a) made interoperable and (b) integrated. And third, in order for the resulting annotations to suit the Semantic Web, they had to be specified by means of an ontology-based vocabulary, and structured by means of ontology-based triples, as hinted above. Therefore, a new annotation scheme had to be devised, based both on ontologies and on this type of triples, which allowed for the combination and the integration of the annotations of any set of linguistic annotation tools. This annotation scheme was considered a fundamental part of the model proposed here, and its development was, accordingly, another major objective of the present work. All these goals, aims and objectives could be re-stated more clearly as follows: Goal 1: Development of a set of ontologies for the formalisation of the linguistic knowledge relating linguistic annotation. Sub-goal 1.1: Ontological formalisation of the EAGLES (1996a; 1996b) de facto standards for morphosyntactic and syntactic annotation, in a way that helps respect the triple structure recommended for annotations in these works (which is isomorphic to the triple structures used in the context of the Semantic Web). Sub-goal 1.2: Incorporation into this preliminary ontological formalisation of other existing standards and standard proposals relating the levels mentioned above, such as those currently under development within ISO/TC 37 (the ISO Technical Committee dealing with Terminology, which deals also with linguistic resources and annotations). Sub-goal 1.3: Generalisation and extension of the recommendations in EAGLES (1996a; 1996b) and ISO/TC 37 to the semantic level, for which no ISO/TC 37 standards have been developed yet. Sub-goal 1.4: Ontological formalisation of the generalisations and/or extensions obtained in the previous sub-goal as generalisations and/or extensions of the corresponding ontology (or ontologies). Sub-goal 1.5: Ontological formalisation of the knowledge required to link, combine and unite the knowledge represented in the previously developed ontology (or ontologies). Goal 2: Development of OntoTag’s annotation scheme, a standard-based abstract scheme for the hybrid (linguistically-motivated and ontological-based) annotation of texts. Sub-goal 2.1: Development of the standard-based morphosyntactic annotation level of OntoTag’s scheme. This level should include, and possibly extend, the recommendations of EAGLES (1996a) and also the recommendations included in the ISO/MAF (2008) standard draft. Sub-goal 2.2: Development of the standard-based syntactic annotation level of the hybrid abstract scheme. This level should include, and possibly extend, the recommendations of EAGLES (1996b) and the ISO/SynAF (2010) standard draft. Sub-goal 2.3: Development of the standard-based semantic annotation level of OntoTag’s (abstract) scheme. Sub-goal 2.4: Development of the mechanisms for a convenient integration of the three annotation levels already mentioned. These mechanisms should take into account the recommendations included in the ISO/LAF (2009) standard draft. Goal 3: Design of OntoTag’s (abstract) annotation architecture, an abstract architecture for the hybrid (semantic) annotation of texts (i) that facilitates the integration and interoperation of different linguistic annotation tools, and (ii) whose results comply with OntoTag’s annotation scheme. Sub-goal 3.1: Specification of the decanting processes that allow for the classification and separation, according to their corresponding levels, of the results of the linguistic tools annotating at several different levels. Sub-goal 3.2: Specification of the standardisation processes that allow (a) complying with the standardisation requirements of OntoTag’s annotation scheme, as well as (b) combining the results of those linguistic tools that share some level of annotation. Sub-goal 3.3: Specification of the merging processes that allow for the combination of the output annotations and the interoperation of those linguistic tools that share some level of annotation. Sub-goal 3.4: Specification of the merge processes that allow for the integration of the results and the interoperation of those tools performing their annotations at different levels. Goal 4: Generation of OntoTagger’s schema, a concrete instance of OntoTag’s abstract scheme for a concrete set of linguistic annotations. These linguistic annotations result from the tools and the resources available in the research group, namely • Bitext’s DataLexica (http://www.bitext.com/EN/datalexica.asp), • LACELL’s (POS) tagger (http://www.um.es/grupos/grupo-lacell/quees.php), • Connexor’s FDG (http://www.connexor.eu/technology/machinese/glossary/fdg/), and • EuroWordNet (Vossen et al., 1998). This schema should help evaluate OntoTag’s underlying hypotheses, stated below. Consequently, it should implement, at least, those levels of the abstract scheme dealing with the annotations of the set of tools considered in this implementation. This includes the morphosyntactic, the syntactic and the semantic levels. Goal 5: Implementation of OntoTagger’s configuration, a concrete instance of OntoTag’s abstract architecture for this set of linguistic tools and annotations. This configuration (1) had to use the schema generated in the previous goal; and (2) should help support or refute the hypotheses of this work as well (see the next section). Sub-goal 5.1: Implementation of the decanting processes that facilitate the classification and separation of the results of those linguistic resources that provide annotations at several different levels (on the one hand, LACELL’s tagger operates at the morphosyntactic level and, minimally, also at the semantic level; on the other hand, FDG operates at the morphosyntactic and the syntactic levels and, minimally, at the semantic level as well). Sub-goal 5.2: Implementation of the standardisation processes that allow (i) specifying the results of those linguistic tools that share some level of annotation according to the requirements of OntoTagger’s schema, as well as (ii) combining these shared level results. In particular, all the tools selected perform morphosyntactic annotations and they had to be conveniently combined by means of these processes. Sub-goal 5.3: Implementation of the merging processes that allow for the combination (and possibly the improvement) of the annotations and the interoperation of the tools that share some level of annotation (in particular, those relating the morphosyntactic level, as in the previous sub-goal). Sub-goal 5.4: Implementation of the merging processes that allow for the integration of the different standardised and combined annotations aforementioned, relating all the levels considered. Sub-goal 5.5: Improvement of the semantic level of this configuration by adding a named entity recognition, (sub-)classification and annotation subsystem, which also uses the named entities annotated to populate a domain ontology, in order to provide a concrete application of the present work in the two areas involved (the Semantic Web and Corpus Linguistics). 3. MAIN RESULTS: ASSESSMENT OF ONTOTAG’S UNDERLYING HYPOTHESES The model developed in the present thesis tries to shed some light on (i) whether linguistic annotation tools can effectively interoperate; (ii) whether their results can be combined and integrated; and, if they can, (iii) how they can, respectively, interoperate and be combined and integrated. Accordingly, several hypotheses had to be supported (or rejected) by the development of the OntoTag model and OntoTagger (its implementation). The hypotheses underlying OntoTag are surveyed below. Only one of the hypotheses (H.6) was rejected; the other five could be confirmed. H.1 The annotations of different levels (or layers) can be integrated into a sort of overall, comprehensive, multilayer and multilevel annotation, so that their elements can complement and refer to each other. • CONFIRMED by the development of: o OntoTag’s annotation scheme, o OntoTag’s annotation architecture, o OntoTagger’s (XML, RDF, OWL) annotation schemas, o OntoTagger’s configuration. H.2 Tool-dependent annotations can be mapped onto a sort of tool-independent annotations and, thus, can be standardised. • CONFIRMED by means of the standardisation phase incorporated into OntoTag and OntoTagger for the annotations yielded by the tools. H.3 Standardisation should ease: H.3.1: The interoperation of linguistic tools. H.3.2: The comparison, combination (at the same level and layer) and integration (at different levels or layers) of annotations. • H.3 was CONFIRMED by means of the development of OntoTagger’s ontology-based configuration: o Interoperation, comparison, combination and integration of the annotations of three different linguistic tools (Connexor’s FDG, Bitext’s DataLexica and LACELL’s tagger); o Integration of EuroWordNet-based, domain-ontology-based and named entity annotations at the semantic level. o Integration of morphosyntactic, syntactic and semantic annotations. H.4 Ontologies and Semantic Web technologies (can) play a crucial role in the standardisation of linguistic annotations, by providing consensual vocabularies and standardised formats for annotation (e.g., RDF triples). • CONFIRMED by means of the development of OntoTagger’s RDF-triple-based annotation schemas. H.5 The rate of errors introduced by a linguistic tool at a given level, when annotating, can be reduced automatically by contrasting and combining its results with the ones coming from other tools, operating at the same level. However, these other tools might be built following a different technological (stochastic vs. rule-based, for example) or theoretical (dependency vs. HPS-grammar-based, for instance) approach. • CONFIRMED by the results yielded by the evaluation of OntoTagger. H.6 Each linguistic level can be managed and annotated independently. • REJECTED: OntoTagger’s experiments and the dependencies observed among the morphosyntactic annotations, and between them and the syntactic annotations. In fact, Hypothesis H.6 was already rejected when OntoTag’s ontologies were developed. We observed then that several linguistic units stand on an interface between levels, belonging thereby to both of them (such as morphosyntactic units, which belong to both the morphological level and the syntactic level). Therefore, the annotations of these levels overlap and cannot be handled independently when merged into a unique multileveled annotation. 4. OTHER MAIN RESULTS AND CONTRIBUTIONS First, interoperability is a hot topic for both the linguistic annotation community and the whole Computer Science field. The specification (and implementation) of OntoTag’s architecture for the combination and integration of linguistic (annotation) tools and annotations by means of ontologies shows a way to make these different linguistic annotation tools and annotations interoperate in practice. Second, as mentioned above, the elements involved in linguistic annotation were formalised in a set (or network) of ontologies (OntoTag’s linguistic ontologies). • On the one hand, OntoTag’s network of ontologies consists of − The Linguistic Unit Ontology (LUO), which includes a mostly hierarchical formalisation of the different types of linguistic elements (i.e., units) identifiable in a written text; − The Linguistic Attribute Ontology (LAO), which includes also a mostly hierarchical formalisation of the different types of features that characterise the linguistic units included in the LUO; − The Linguistic Value Ontology (LVO), which includes the corresponding formalisation of the different values that the attributes in the LAO can take; − The OIO (OntoTag’s Integration Ontology), which  Includes the knowledge required to link, combine and unite the knowledge represented in the LUO, the LAO and the LVO;  Can be viewed as a knowledge representation ontology that describes the most elementary vocabulary used in the area of annotation. • On the other hand, OntoTag’s ontologies incorporate the knowledge included in the different standards and recommendations for linguistic annotation released so far, such as those developed within the EAGLES and the SIMPLE European projects or by the ISO/TC 37 committee: − As far as morphosyntactic annotations are concerned, OntoTag’s ontologies formalise the terms in the EAGLES (1996a) recommendations and their corresponding terms within the ISO Morphosyntactic Annotation Framework (ISO/MAF, 2008) standard; − As for syntactic annotations, OntoTag’s ontologies incorporate the terms in the EAGLES (1996b) recommendations and their corresponding terms within the ISO Syntactic Annotation Framework (ISO/SynAF, 2010) standard draft; − Regarding semantic annotations, OntoTag’s ontologies generalise and extend the recommendations in EAGLES (1996a; 1996b) and, since no stable standards or standard drafts have been released for semantic annotation by ISO/TC 37 yet, they incorporate the terms in SIMPLE (2000) instead; − The terms coming from all these recommendations and standards were supplemented by those within the ISO Data Category Registry (ISO/DCR, 2008) and also of the ISO Linguistic Annotation Framework (ISO/LAF, 2009) standard draft when developing OntoTag’s ontologies. Third, we showed that the combination of the results of tools annotating at the same level can yield better results (both in precision and in recall) than each tool separately. In particular, 1. OntoTagger clearly outperformed two of the tools integrated into its configuration, namely DataLexica and FDG in all the combination sub-phases in which they overlapped (i.e. POS tagging, lemma annotation and morphological feature annotation). As far as the remaining tool is concerned, i.e. LACELL’s tagger, it was also outperformed by OntoTagger in POS tagging and lemma annotation, and it did not behave better than OntoTagger in the morphological feature annotation layer. 2. As an immediate result, this implies that a) This type of combination architecture configurations can be applied in order to improve significantly the accuracy of linguistic annotations; and b) Concerning the morphosyntactic level, this could be regarded as a way of constructing more robust and more accurate POS tagging systems. Fourth, Semantic Web annotations are usually performed by humans or else by machine learning systems. Both of them leave much to be desired: the former, with respect to their annotation rate; the latter, with respect to their (average) precision and recall. In this work, we showed how linguistic tools can be wrapped in order to annotate automatically Semantic Web pages using ontologies. This entails their fast, robust and accurate semantic annotation. As a way of example, as mentioned in Sub-goal 5.5, we developed a particular OntoTagger module for the recognition, classification and labelling of named entities, according to the MUC and ACE tagsets (Chinchor, 1997; Doddington et al., 2004). These tagsets were further specified by means of a domain ontology, namely the Cinema Named Entities Ontology (CNEO). This module was applied to the automatic annotation of ten different web pages containing cinema reviews (that is, around 5000 words). In addition, the named entities annotated with this module were also labelled as instances (or individuals) of the classes included in the CNEO and, then, were used to populate this domain ontology. • The statistical results obtained from the evaluation of this particular module of OntoTagger can be summarised as follows. On the one hand, as far as recall (R) is concerned, (R.1) the lowest value was 76,40% (for file 7); (R.2) the highest value was 97, 50% (for file 3); and (R.3) the average value was 88,73%. On the other hand, as far as the precision rate (P) is concerned, (P.1) its minimum was 93,75% (for file 4); (R.2) its maximum was 100% (for files 1, 5, 7, 8, 9, and 10); and (R.3) its average value was 98,99%. • These results, which apply to the tasks of named entity annotation and ontology population, are extraordinary good for both of them. They can be explained on the basis of the high accuracy of the annotations provided by OntoTagger at the lower levels (mainly at the morphosyntactic level). However, they should be conveniently qualified, since they might be too domain- and/or language-dependent. It should be further experimented how our approach works in a different domain or a different language, such as French, English, or German. • In any case, the results of this application of Human Language Technologies to Ontology Population (and, accordingly, to Ontological Engineering) seem very promising and encouraging in order for these two areas to collaborate and complement each other in the area of semantic annotation. Fifth, as shown in the State of the Art of this work, there are different approaches and models for the semantic annotation of texts, but all of them focus on a particular view of the semantic level. Clearly, all these approaches and models should be integrated in order to bear a coherent and joint semantic annotation level. OntoTag shows how (i) these semantic annotation layers could be integrated together; and (ii) they could be integrated with the annotations associated to other annotation levels. Sixth, we identified some recommendations, best practices and lessons learned for annotation standardisation, interoperation and merge. They show how standardisation (via ontologies, in this case) enables the combination, integration and interoperation of different linguistic tools and their annotations into a multilayered (or multileveled) linguistic annotation, which is one of the hot topics in the area of Linguistic Annotation. And last but not least, OntoTag’s annotation scheme and OntoTagger’s annotation schemas show a way to formalise and annotate coherently and uniformly the different units and features associated to the different levels and layers of linguistic annotation. This is a great scientific step ahead towards the global standardisation of this area, which is the aim of ISO/TC 37 (in particular, Subcommittee 4, dealing with the standardisation of linguistic annotations and resources).

Overlapping species boundaries and hybridization within the Monastraea "annularis" reef coral complex in the Pleistocene of the Bahama Islands

Recent molecular analyses indicate that many reef coral species belong to hybridizing species complexes or "syngameons." Such complexes consist of numerous genetically distinct-species or lineages, which periodically split and/or fuse as they extend through time. During splitting and fusion, morphologic intermediates form and species overlap. Here we focus on processes associated with lineage fusion, specifically introgressive hybridization, and the recognition of such hybridization in the fossil record. Our approach involves comparing patterns of ecologic and morphologic overlap in genetically characterized modern species with fossil representatives of the same or closely related species. We similarly consider the long-term consequences of past hybridization on the structure of modern-day species boundaries. Our study involves the species complex Montastraea annularis s.l. and is based in the Bahamas, where, unlike other Caribbean locations, two of the three members of the complex today are not genetically distinct. We measured and collected colonies along linear transects across Pleistocene reef terraces of last interglacial age (approximately 125 Ka) on the islands of San Salvador, Andros, and Great Inagua. We performed quantitative ecologic and morphologic analyses of the fossil data, and compared patterns of overlap among species with data from modern localities where species are and are not genetically distinct. Ecologic and morphologic analyses reveal "moderate" overlap (>10%, but statistically significant differences) and sometimes "high" overlap (no statistically significant differences) among Pleistocene growth forms (= "species"). Ecologic analyses show that three species (massive, column, organ-pipe) co-occurred. Although organ-pipes had higher abundances in patch reef environments, columnar and massive species exhibited broad, completely overlapping distributions and had abundances that were not related to reef environment. For morphometric analyses, we used multivariate discriminant analysis on landmark data and linear measurements. The results show that columnar species overlap "moderately" with organ-pipe and massive species. Comparisons with genetically characterized colonies from Panama show that the Pleistocene Bahamas species have intermediate morphologies, and that the observed "moderate" overlap differs from the morphologic separation among the three modern species. In contrast, massive and columnar species from the Pleistocene of the Dominican Republic comprise distinct morphologic clusters, similar to the modern species; organ-pipe species exhibit "low" overlap (

100-Gb/s point-to-point solutions for long-reach passive optical networks in sparse rural and urban areas

Long reach-passive optical networks (LR-PON) are being proposed as a means of enabling ubiquitous fiber-to-the-home (FTTH) by massive sharing of network resources and therefore reducing per customer costs to affordable levels. In this paper, we analyze the chain solutions for LR-PON deployment in urban and rural areas at 100-Gb/s point-to-point transmission using dual polarization-quaternary phase shift-keying (DP-QPSK) modulation. The numerical analysis shows that with appropriate finite impulse response (FIR) filter designs, 100-Gb/s transmission can be achieved with at least 512 way split and up to 160 km total distance, which is sufficient for many of the optical paths in a practical situation, for point-to-point link from one LR-PON to another LR-PON through the optical switch at the metro nodes and across a core light path through the core network without regeneration.

Direct Observation of Tetragonal Distortion in Epitaxial Structures through Secondary Peak Split in a Synchrotron Radiation Renninger Scan

This paper reports a direct observation of an interesting split of the (022)(022) four-beam secondary peak into two (022) and (022) three-beam peaks, in a synchrotron radiation Renninger scan (phi-scan), as an evidence of the layer tetragonal distortion in two InGaP/GaAs (001) epitaxial structures with different thicknesses. The thickness, composition, (a perpendicular to) perpendicular lattice parameter, and (01) in-plane lattice parameter of the two epitaxial ternary layers were obtained from rocking curves (omega-scan) as well as from the simulation of the (022)(022) split, and then, it allowed for the determination of the perpendicular and parallel (in-plane) strains. Furthermore, (022)(022) omega:phi mappings were measured in order to exhibit the multiple diffraction condition of this four-beam case with their split measurement.

Minor and major consolidations in inverse DEA:definition and determination

Many production systems have acquisition and merge operations to increase productivity. This paper proposes a novel method to anticipate whether a merger in a market is generating a major or a minor consolidation, using InvDEA model. A merger between two or more decision making units (DMUs) producing a single merged DMU that affects the efficiency frontier, defined by the pre-consolidation market conditions, is called a major consolidation. The corresponding alternative case is called a minor consolidation. A necessary and sufficient condition to distinguish the two types of consolidations is proven and two numerical illustrations in banking and supply chain management are discussed. The crucial importance of anticipating the magnitude of a consolidation in a market is outlined.

Lesões esportivas em atletas com deficiencia visual

Universidade Estadual de Campinas . Faculdade de Educação Física

Does a final rinse to remove smear layer interfere on dentin permeability of root canals?

Objective. The objective of this study was to assess the influence of different final irrigating solutions on dentin permeability and smear layer removal using the same specimens and relate the results obtained. Study design. Forty anterior human teeth were instrumented and divided into 4 groups (n = 10) at the final rinse step, according to the irrigant used: G I (control) - 1% NaOCl; G II - 17% EDTA; G III - 17% EDTAT; and G IV - Biopure MTAD. The canals were filled with 0.5% methylene blue and maintained in bottles for 48 hours. The roots were transversally split in coronal, middle, and apical fragments. The specimens were photographed and analyzed regarding dye penetration. The fragments were then axially split and prepared for SEM. The photomicrographs were analyzed and qualified by scores. Results. Only the EDTA-T group exhibited statistical difference in which the apical third had less dentin permeability (P < .05). When a decalcifying agent was used, smear layer was removed, which did not happen in the NaOCl group. Regarding smear layer removal, differences were found only in the EDTA group in which the apical third presented more smear layer (P < .05). No correlation was found for both studies (r = 0.4207). Conclusions. There was not an even relationship between the results from both studies, which inferes that higher or lower dentinal permeability does not necessarily correspond to a higher or lower amount of smear layer. The analysis of dentin permeability and smear layer removal was shown to be a feasible procedure using the same specimens. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107: e47-e51)

Multi-fluorescent silica colloids for encoding large combinatorial libraries

Large chemical libraries can be synthesized on solid-support beads by the combinatorial split-and-mix method. A major challenge associated with this type of library synthesis is distinguishing between the beads and their attached compounds. A new method of encoding these solid-support beads, 'colloidal bar-coding', involves attaching fluorescent silica colloids ('reporters') to the beads as they pass through the compound synthesis, thereby creating a fluorescent bar code on each bead. In order to obtain sufficient reporter varieties to bar code extremely large libraries, many of the reporters must contain multiple fluorescent dyes. We describe here the synthesis and spectroscopic analysis of various mono- and multi-fluorescent silica particles for this purpose. It was found that by increasing the amount of a single dye introduced into the particle reaction mixture, mono- fluorescent silica particles of increasing intensities could be prepared. This increase was highly reproducible and was observed for six different fluorescent dyes. Multi-fluorescent silica particles containing up to six fluorescent dyes were also prepared. The resultant emission intensity of each dye in the multi-fluorescent particles was found to be dependent upon a number of factors; the hydrolysis rate of each silane-dye conjugate, the magnitude of the inherent emission intensity of each dye within the silica matrix, and energy transfer effects between dyes. We show that by varying the relative concentration of each silane-dye conjugate in the synthesis of multi-fluorescent particles, it is possible to change and optimize the resultant emission intensity of each dye to enable viewing in a fluorescence detection instrument.

Synthesis of optically complex core-shell colloidal suspensions: Pathways to multiplexed biological screening

The ability to generate enormous random libraries of DNA probes via split-and-mix synthesis on solid supports is an important biotechnological application of colloids that has not been fully utilized to date. To discriminate between colloid-based DNA probes each colloidal particle must be 'encoded' so it is distinguishable from all other particles. To this end, we have used novel particle synthesis strategies to produce large numbers of optically encoded particle suitable for DNA library synthesis. Multifluorescent particles with unique and reproducible optical signatures (i.e., fluorescence and light-scattering attributes) suitable for high-throughput flow cytometry have been produced. In the spectroscopic study presented here, we investigated the optical characteristics of multi-fluorescent particles that were synthesized by coating silica 'core' particles with up to six different fluorescent dye shells alternated with non-fluorescent silica 'spacer' shells. It was observed that the diameter of the particles increased by up to 20% as a result of the addition of twelve concentric shells and that there was a significant reduction in fluorescence emission intensities from inner shells as an increasing number of shells were deposited.