The influence of economic incentives linked to road safety indicators on accidents: The case of toll concessions in Spain

The goal of this paper is to evaluate whether the incentives incorporated in toll highway concession contracts in order to encourage private operators to adopt measures to reduce accidents are actually effective at improving safety. To this end, we implemented negative binomial regression models using information about highway characteristics and accident data from toll highway concessions in Spain from 2007 to 2009. Our results show that even though road safety is highly influenced by variables that are not managed by the contractor, such as the annual average daily traffic (AADT), the percentage of heavy vehicles on the highway, number of lanes, number of intersections and average speed; the implementation of these incentives has a positive influence on the reduction of accidents and injuries. Consequently, this measure seems to be an effective way of improving safety performance in road networks.

p-medicine: a medical informatics platform for integrated large scale heterogeneous patient data

Secure access to patient data is becoming of increasing importance, as medical informatics grows in significance, to both assist with population health studies, and patient specific medicine in support of treatment. However, assembling the many different types of data emanating from the clinic is in itself a difficulty, and doing so across national borders compounds the problem. In this paper we present our solution: an easy to use distributed informatics platform embedding a state of the art data warehouse incorporating a secure pseudonymisation system protecting access to personal healthcare data. Using this system, a whole range of patient derived data, from genomics to imaging to clinical records, can be assembled and linked, and then connected with analytics tools that help us to understand the data. Research performed in this environment will have immediate clinical impact for personalised patient healthcare.

A Personal Agent Architecture for Task Automation in the Web of Data. Bringing intelligence to everyday tasks

Internet está evolucionando hacia la conocida como Live Web. En esta nueva etapa en la evolución de Internet, se pone al servicio de los usuarios multitud de streams de datos sociales. Gracias a estas fuentes de datos, los usuarios han pasado de navegar por páginas web estáticas a interacturar con aplicaciones que ofrecen contenido personalizado, basada en sus preferencias. Cada usuario interactúa a diario con multiples aplicaciones que ofrecen notificaciones y alertas, en este sentido cada usuario es una fuente de eventos, y a menudo los usuarios se sienten desbordados y no son capaces de procesar toda esa información a la carta. Para lidiar con esta sobresaturación, han aparecido múltiples herramientas que automatizan las tareas más habituales, desde gestores de bandeja de entrada, gestores de alertas en redes sociales, a complejos CRMs o smart-home hubs. La contrapartida es que aunque ofrecen una solución a problemas comunes, no pueden adaptarse a las necesidades de cada usuario ofreciendo una solucion personalizada. Los Servicios de Automatización de Tareas (TAS de sus siglas en inglés) entraron en escena a partir de 2012 para dar solución a esta liminación. Dada su semejanza, estos servicios también son considerados como un nuevo enfoque en la tecnología de mash-ups pero centra en el usuarios. Los usuarios de estas plataformas tienen la capacidad de interconectar servicios, sensores y otros aparatos con connexión a internet diseñando las automatizaciones que se ajustan a sus necesidades. La propuesta ha sido ámpliamante aceptada por los usuarios. Este hecho ha propiciado multitud de plataformas que ofrecen servicios TAS entren en escena. Al ser un nuevo campo de investigación, esta tesis presenta las principales características de los TAS, describe sus componentes, e identifica las dimensiones fundamentales que los defines y permiten su clasificación. En este trabajo se acuña el termino Servicio de Automatización de Tareas (TAS) dando una descripción formal para estos servicios y sus componentes (llamados canales), y proporciona una arquitectura de referencia. De igual forma, existe una falta de herramientas para describir servicios de automatización, y las reglas de automatización. A este respecto, esta tesis propone un modelo común que se concreta en la ontología EWE (Evented WEb Ontology). Este modelo permite com parar y equiparar canales y automatizaciones de distintos TASs, constituyendo un aporte considerable paraa la portabilidad de automatizaciones de usuarios entre plataformas. De igual manera, dado el carácter semántico del modelo, permite incluir en las automatizaciones elementos de fuentes externas sobre los que razonar, como es el caso de Linked Open Data. Utilizando este modelo, se ha generado un dataset de canales y automatizaciones, con los datos obtenidos de algunos de los TAS existentes en el mercado. Como último paso hacia el lograr un modelo común para describir TAS, se ha desarrollado un algoritmo para aprender ontologías de forma automática a partir de los datos del dataset. De esta forma, se favorece el descubrimiento de nuevos canales, y se reduce el coste de mantenimiento del modelo, el cual se actualiza de forma semi-automática. En conclusión, las principales contribuciones de esta tesis son: i) describir el estado del arte en automatización de tareas y acuñar el término Servicio de Automatización de Tareas, ii) desarrollar una ontología para el modelado de los componentes de TASs y automatizaciones, iii) poblar un dataset de datos de canales y automatizaciones, usado para desarrollar un algoritmo de aprendizaje automatico de ontologías, y iv) diseñar una arquitectura de agentes para la asistencia a usuarios en la creación de automatizaciones. ABSTRACT The new stage in the evolution of the Web (the Live Web or Evented Web) puts lots of social data-streams at the service of users, who no longer browse static web pages but interact with applications that present them contextual and relevant experiences. Given that each user is a potential source of events, a typical user often gets overwhelmed. To deal with that huge amount of data, multiple automation tools have emerged, covering from simple social media managers or notification aggregators to complex CRMs or smart-home Hub/Apps. As a downside, they cannot tailor to the needs of every single user. As a natural response to this downside, Task Automation Services broke in the Internet. They may be seen as a new model of mash-up technology for combining social streams, services and connected devices from an end-user perspective: end-users are empowered to connect those stream however they want, designing the automations they need. The numbers of those platforms that appeared early on shot up, and as a consequence the amount of platforms following this approach is growing fast. Being a novel field, this thesis aims to shed light on it, presenting and exemplifying the main characteristics of Task Automation Services, describing their components, and identifying several dimensions to classify them. This thesis coins the term Task Automation Services (TAS) by providing a formal definition of them, their components (called channels), as well a TAS reference architecture. There is also a lack of tools for describing automation services and automations rules. In this regard, this thesis proposes a theoretical common model of TAS and formalizes it as the EWE ontology This model enables to compare channels and automations from different TASs, which has a high impact in interoperability; and enhances automations providing a mechanism to reason over external sources such as Linked Open Data. Based on this model, a dataset of components of TAS was built, harvesting data from the web sites of actual TASs. Going a step further towards this common model, an algorithm for categorizing them was designed, enabling their discovery across different TAS. Thus, the main contributions of the thesis are: i) surveying the state of the art on task automation and coining the term Task Automation Service; ii) providing a semantic common model for describing TAS components and automations; iii) populating a categorized dataset of TAS components, used to learn ontologies of particular domains from the TAS perspective; and iv) designing an agent architecture for assisting users in setting up automations, that is aware of their context and acts in consequence.

A Constitutively “Phosphorylated” Guanylyl Cyclase-linked Atrial Natriuretic Peptide Receptor Mutant Is Resistant to Desensitization

Dephosphorylation of the natriuretic peptide receptor-A (NPR-A) is hypothesized to mediate its desensitization in response to atrial natriuretic peptide (ANP) binding. Recently, we identified six phosphorylation sites within the kinase homology domain of NPR-A and determined that the conversion of these residues to alanine abolished the ability of the receptor to be phosphorylated or to be activated by ANP and ATP. In an attempt to generate a form of NPR-A that mimics a fully phosphorylated receptor but that is resistant to dephosphorylation, we engineered a receptor variant (NPR-A-6E) containing glutamate substitutions at all six phosphorylation sites. Consistent with the known ability of negatively charged glutamate residues to substitute functionally, in some cases, for phosphorylated residues, we found that NPR-A-6E was activated 10-fold by ANP and ATP. As determined by guanylyl cyclase assays, the hormone-stimulated activity of the wild-type receptor declined over time in membrane preparations in vitro, and this loss was blocked by the serine/threonine protein phosphatase inhibitor microcystin. In contrast, the activity of NPR-A-6E was more linear with time and was unaffected by microcystin. The nonhydrolyzable ATP analogue adenosine 5′-(β,γ-imino)-triphosphate was half as effective as ATP in stimulating the wild-type receptor but was equally as potent in stimulating NPR-A-6E, suggesting that ATP is required to keep the wild-type but not 6E variant phosphorylated. Finally, the desensitization of NPR-A-6E in whole cells was markedly blunted compared with that of the wild-type receptor, consistent with its inability to shed the negative charge from its kinase homology domain via dephosphorylation. These data provide the first direct test of the requirement for dephosphorylation in guanylyl cyclase desensitization and they indicate that it is an essential component of this process.

Adapter proteins SLP-76 and BLNK both are expressed by murine macrophages and are linked to signaling via Fcγ receptors I and II/III

The SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kDa) adapter protein is expressed in T cells and myeloid cells, whereas its homologue BLNK (B cell linker protein) is expressed in B cells. SLP-76 and BLNK link immunoreceptor tyrosine-based activation motif-containing receptors to signaling molecules that include phospholipase C-γ, mitogen-activated protein kinases, and the GTPases Ras and Rho. SLP-76 plays a critical role in T cell receptor, FcɛRI and gpVI collagen receptor signaling, and participates in signaling via FcγR and killer cell inhibitory receptors. BLNK plays a critical role in B cell receptor signaling. We show that murine bone marrow-derived macrophages express both SLP-76 and BLNK. Selective ligation of FcγRI and FcγRII/III resulted in tyrosine phosphorylation of both SLP-76 and BLNK. SLP-76−/− bone marrow-derived macrophages display FcγR-mediated tyrosine phosphorylation of Syk, phospholipase C-γ2, and extracellular signal regulated kinases 1 and 2, and normal FcγR-dependent phagocytosis. These data suggest that both SLP-76 and BLNK are coupled to FcγR signaling in murine macrophages.

Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway

PTEN/MMAC1 is a tumor suppressor gene located on chromosome 10q23. Inherited PTEN/MMAC1 mutations are associated with a cancer predisposition syndrome known as Cowden’s disease. Somatic mutation of PTEN has been found in a number of malignancies, including glioblastoma, melanoma, and carcinoma of the prostate and endometrium. The protein product (PTEN) encodes a dual-specificity protein phosphatase and in addition can dephosphorylate certain lipid substrates. Herein, we show that PTEN protein induces a G1 block when reconstituted in PTEN-null cells. A PTEN mutant associated with Cowden’s disease (PTEN;G129E) has protein phosphatase activity yet is defective in dephosphorylating inositol 1,3,4,5-tetrakisphosphate in vitro and fails to arrest cells in G1. These data suggest a link between induction of a cell-cycle block by PTEN and its ability to dephosphorylate, in vivo, phosphatidylinositol 3,4,5-trisphosphate. In keeping with this notion, PTEN can inhibit the phosphatidylinositol 3,4,5-trisphosphate-dependent Akt kinase, a downstream target of phosphatidylinositol 3-kinase, and constitutively active, but not wild-type, Akt overrides a PTEN G1 arrest. Finally, tumor cells lacking PTEN contain high levels of activated Akt, suggesting that PTEN is necessary for the appropriate regulation of the phosphatidylinositol 3-kinase/Akt pathway.

Human Immunodeficiency Virus Reverse Transcriptase and Protease Sequence Database: an expanded data model integrating natural language text and sequence analysis programs

The HIV Reverse Transcriptase and Protease Sequence Database is an on-line relational database that catalogs evolutionary and drug-related sequence variation in the human immunodeficiency virus (HIV) reverse transcriptase (RT) and protease enzymes, the molecular targets of anti-HIV therapy (http://hivdb.stanford.edu). The database contains a compilation of nearly all published HIV RT and protease sequences, including submissions from International Collaboration databases and sequences published in journal articles. Sequences are linked to data about the source of the sequence sample and the antiretroviral drug treatment history of the individual from whom the isolate was obtained. During the past year 3500 sequences have been added and the data model has been expanded to include drug susceptibility data on sequenced isolates. Database content has also been integrated with didactic text and the output of two sequence analysis programs.

Three-dimensional model of the potyviral genome-linked protein.

The full sequence of the genome-linked viral protein (VPg) cistron located in the central part of potato virus Y (common strain) genome has been identified. The VPg gene codes for a protein of 188 amino acids, with significant homology to other known potyviral VPg polypeptides. A three-dimensional model structure of VPg is proposed on the basis of similarity of hydrophobic-hydrophilic residue distribution to the sequence of malate dehydrogenase of known crystal structure. The 5' end of the viral RNA can be fitted to interact with the protein through the exposed hydroxyl group of Tyr-64, in agreement with experimental data. The complex favors stereochemically the formation of a phosphodiester bond [5'-(O4-tyrosylphospho)adenylate] typical for representatives of picornavirus-like viruses. The chemical mechanisms of viral RNA binding to VPg are discussed on the basis of the model structure of protein-RNA complex.

GSP-1 genes are linked to the grain hardness locus (Ha) on wheat chromosome 5D.

An important determinant of wheat grain quality is the hardness of the grain. The trait is controlled by a major locus, Ha, on the short arm of chromosome 5D. Purified starch granules from soft-grained wheats have associated with them 15-kDa polypeptides called grain softness proteins (GSPs) or "friabilins." Genes that encode one family of closely related GSP polypeptides - GSP-1 genes - were mapped using chromosome substitution lines to the group 5 chromosomes. An F2 population segregating for hard and soft alleles at the Ha locus on a near-isogenic background was used in a single-seed study of the inheritance of grain softness and of GSP-1 alleles. Grain softness versus grain hardness was inherited in a 3:1 ratio. The presence versus absence of GSPs in single seed starch preparations was coinherited with grain softness versus hardness. This showed that grain softness is primarily determined by seed, and not by maternal, genotype. In addition, no recombination was detected in 44 F2 plants between GSP-1 restriction fragment length polymorphisms and Ha alleles. Differences between hard and soft wheat grains in membrane structure and lipid extractability have been described and, of the three characterized proteins that are part of the mixture of 15-kDa polypeptides called GSPs, at least two, and probably all three, are proteins that bind polar lipids. The data are interpreted to suggest that the Ha locus may encode one or more members of a large family of lipid-binding proteins.

Progression of human breast cancers to the metastatic state is linked to hydroxyl radical-induced DNA damage.

Hydroxyl radical damage in metastatic tumor DNA was elucidated in women with breast cancer, and a comparison was made with nonmetastatic tumor DNA. The damage was identified by using statistical models of modified base and Fourier transform-infrared spectral data. The modified base models revealed a greater than 2-fold increase in hydroxyl radical damage in the metastatic tumor DNA compared with the nonmetastatic tumor DNA. The metastatic tumor DNA also exhibited substantially greater base diversity than the nonmetastatic DNA, and a progression of radical-induced base damage was found to be associated with the growth of metastatic tumors. A three-dimensional plot of principal components from factor analysis, derived from infrared spectral data, also showed that the metastatic tumor DNA was substantially more diverse than the tightly grouped nonmetastatic tumor DNA. These cohesive, independently derived findings suggest that the hydroxyl radical generates DNA phenotypes with various metastatic potentials that likely contribute to the diverse physiological properties and heterogeneity characteristic of metastatic cell populations.

Genetic heterogeneity in cystinuria: the SLC3A1 gene is linked to type I but not to type III cystinuria.

Cystinuria is an autosomal recessive amino-aciduria where three urinary phenotypes have been described (I, II, and III). An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. To assess whether mutations in SLC3A1 are involved in different cystinuria phenotypes, linkage with this gene and its nearest marker (D2S119) was analyzed in 22 families with type I and/or type III cystinuria. Linkage with heterogeneity was proved (alpha = 0.45; P < 0.008). Type I/I families showed homogeneous linkage to SLC3A1 (Zmax > 3.0 at theta = 0.00; alpha = 1), whereas types I/III and III/III were not linked. Our data suggest that type I cystinuria is due to mutations in the SLC3A1 gene, whereas another locus is responsible for type III. This result establishes genetic heterogeneity for cystinuria, classically considered as a multiallelic monogenic disease.

Complete congruence between gene diversity estimates derived from genotypic data at enzyme and random amplified polymorphic DNA loci in black spruce.

Controversy still exists over the adaptive nature of variation of enzyme loci. In conifers, random amplified polymorphic DNAs (RAPDs) represent a class of marker loci that is unlikely to fall within or be strongly linked to coding DNA. We have compared the genetic diversity in natural populations of black spruce [Picea mariana (Mill.) B.S.P.] using genotypic data at allozyme loci and RAPD loci as well as phenotypic data from inferred RAPD fingerprints. The genotypic data for both allozymes and RAPDs were obtained from at least six haploid megagametophytes for each of 75 sexually mature individuals distributed in five populations. Heterozygosities and population fixation indices were in complete agreement between allozyme loci and RAPD loci. In black spruce, it is more likely that the similar levels of variation detected at both enzyme and RAPD loci are due to such evolutionary forces as migration and the mating system, rather than to balancing selection and overdominance. Furthermore, we show that biased estimates of expected heterozygosity and among-population differentiation are obtained when using allele frequencies derived from dominant RAPD phenotypes.

Open business intelligence: on the importance of data quality awareness in user-friendly data mining

Citizens demand more and more data for making decisions in their daily life. Therefore, mechanisms that allow citizens to understand and analyze linked open data (LOD) in a user-friendly manner are highly required. To this aim, the concept of Open Business Intelligence (OpenBI) is introduced in this position paper. OpenBI facilitates non-expert users to (i) analyze and visualize LOD, thus generating actionable information by means of reporting, OLAP analysis, dashboards or data mining; and to (ii) share the new acquired information as LOD to be reused by anyone. One of the most challenging issues of OpenBI is related to data mining, since non-experts (as citizens) need guidance during preprocessing and application of mining algorithms due to the complexity of the mining process and the low quality of the data sources. This is even worst when dealing with LOD, not only because of the different kind of links among data, but also because of its high dimensionality. As a consequence, in this position paper we advocate that data mining for OpenBI requires data quality-aware mechanisms for guiding non-expert users in obtaining and sharing the most reliable knowledge from the available LOD.

Mineral and chemical composition of hydrothermally altered rocks and sediments from the Middle Valley, ODP Leg 139 data

The Middle Valley segment at the northern end of the Juan de Fuca Ridge is a deep extensional rift blanketed with 200-500 m of Pleistocene turbiditic sediment. Sites 857 and 858 were drilled during Ocean Drilling Program Leg 139 to determine whether these two sites were hydrologically linked end members of an active hydrothermal circulation system. Site 858 was placed in an area of active hydrothermal discharge with fluids up to 270°C venting through anhydrite-bearing mounds on top of altered sediment. The shallow basement of fine-grained basalt that underlies the vents at Site 858 is interpreted as a seamount that was subsequently buried by turbidites. Site 857 was placed 1.6 km south of the Site 858 vents in a zone of high heat flow and numerous seismically imaged ridge-parallel faults. Drilling at Site 857 encountered sediments that are increasingly altered with depth and that overlie a series of mafic sills at depths of 460-940 m below sea floor. Sill margins and adjacent baked sediment are highly altered to magnesian chlorite and crosscut with veins filled with quartz, chlorite, sulfides, epidote, and wairakite. The sill interiors vary from slightly altered, with unaltered plagioclase and clinopyroxene in a mesostasis replaced by chlorite, to local zones of intense alteration and brecciation. In these latter zones, the sill interiors are pervasively replaced by chlorite, epidote, quartz, pyrite, titanite, and rare actinolite. The most complete replacement is associated with brecciated horizons with low recovery and slickensides on fracture surfaces, which we interpret as intersections between faults and the sills. Geochemically, the alteration of the sill complex is reflected in significant whole-rock depletions in Ca, Sr, and Na with corresponding enrichments in Mg, Al, and most metals. The latter results from the formation of conspicuous sulfide poikiloblasts. In contrast, metamorphism of the Site 858 seamount includes incomplete albitization of plagioclase phenocrysts and replacement of sparse mafic phenocrysts. Much of the basement alteration at Site 858 is confined to crosscutting veins except for a highly altered and veined horizon at the contact between basaltic basement and the overlying sediment. The sill complex at Site 857 is more highly depleted in 18O (d18O = 2.4 per mil - 4.7 per mil) and more pervasively replaced by secondary minerals relative to the extrusives at Site 858 (d18O = 4.5 per mil - 5.5 per mil). There is no evidence of significant albitization of the plagioclase at Site 857, suggesting high Ca/Na in the pore fluids. Fluid-inclusion data from hydrothermal minerals in altered mafic rocks and veins at Sites 857 and 858 show a consistency of homogenization temperatures, varying from 245 to 270°C, which is within the range of temperatures observed for the fluids venting at Site 858. The consistency of the fluid inclusion temperatures, the lack of albitization within the Site 857 sills, and the apparently low water/rock ratio collectively suggest that the sill complex at Site 857 is in thermal equilibrium and being altered by a highly evolved Ca-rich fluid similar to the fluids now venting at Site 858. The alteration evident in these two deep crustal drillsites is a result of the ongoing hydrothermal circulation and is consistent with downhole logging results, instrumented borehole results, and hydrothermal fluid chemistry. The pervasive alteration of the laterally extensive sill-sediment complex at Site 857 determines the chemistry of the fluids that are venting at Site 858. The limited alteration of the Site 858 lavas suggests that this basement edifice acts as a penetrator or ventilator for the regional hydrothermal reservoir with much of the flow focussed at the highly altered and veined sediment-basalt contact.

Early Eocene benthic carbon isotope data of ODP Site 208-1263

The early Eocene represents a time of major changes in the global carbon cycle and fluctuations in global temperatures on both short- and long-time scales. These perturbations of the ocean-atmosphere system have been linked to orbital forcing and changes in net organic carbon burial, but accurate age models are required to disentangle the various forcing mechanisms and assess causal relationships. Discrepancies between the employed astrochronological and radioisotopic dating techniques prevent the construction of a robust time frame between ~49 and ~54 Ma. Here we present an astronomically tuned age model for this critical time period based on a new high-resolution benthic d13C record of ODP Site 1263, SE Atlantic. First, we assess three possible tuning options to the stable long-eccentricity cycle (405-kyr), starting from Eocene Thermal Maximum 2 (ETM2, ~54 Ma). Next we compare our record to the existing bulk carbonate d13C record from the equatorial Atlantic (Demerara Rise, ODP Site 1258) to evaluate our three initial age models and compare them with alternative age models previously established for this site. Finally, we refine our preferred age model by expanding our tuning to the 100-kyr eccentricity cycle of the La2010d solution. This solution appears to accurately reflect the long- and short-term eccentricity-related patterns in our benthic d13C record of ODP Site 1263 back to at least 52 Ma and possibly to 54 Ma. Our time scale not only aims to provide a new detailed age model for this period, but it may also serve to enhance our understanding of the response of the climate system to orbital forcing during this super greenhouse period as well as trends in its background state.