Upgrading Relational Legacy Data to eh Semantic Web

In this poster, we describe a framework composed of the R2O mapping language and the ODEMapster processor to upgrade relational legacy data to the Semantic Web. The framework is based on the declarative description of mappings between relational and ontology elements and the exploitation of such mapping descriptions by a generic processor capable of performing both massive and query driven data upgrade

Fund Finder: A case study of database-to-ontology mapping

The mapping between databases and ontologies is a basic problem when trying to "upgrade" deep web content to the semantic web. Our approach suggests the declarative definition of mappings as a way to achieve domain independency and reusability. A specific language (expressive enough to cover some real world mapping situations like lightly structured databases or not 1st normal form ones) is defined for this purpose. Along with this mapping description language, the ODEMapster processor is in charge of carrying out the effective instance data migration. We illustrate this by testing both the mappings definition and processor on a case study

R2O, an extensible and semantically based database-to-ontology mapping language

We present R2O, an extensible and declarative language to describe mappings between relational DB schemas and ontologies implemented in RDF(S) or OWL. R2O provides an extensible set of primitives with welldefined semantics. This language has been conceived expressive enough to cope with complex mapping cases arisen from situations of low similarity between the ontology and the DB models

Actividad antibacteriana de quince antibióticos frente a enterobacterias aisladas en otitis externas caninas crónicas

Hemos estudiado la sensibilidad a quince antimicrobianos de las enterobacterias aisladas en otitis externas caninas crónicas. Se analizaron 20 cepas: 10 Proteus mirabilis, 9 Eseheriehia coli y 1 Klebsiella oxytoca. Se observaron diferencias en sensibilidad en función del género. Todas las cepas de enterobacterias fueron sensibles a ceftazidima, cefoxitina, gentamicina y netilmicina. Todas las cepas de Proteus mirabilis fueron sensibles además a amikacina, cefotaxima, piperacilina, ticarcilina, ciprofloxacina, enrofloxacina y marbofloxacina. En el caso de E. coli, todas las cepas fueron sensibles a tobramicina, además de a los 4 antibióticos descritos para el totaí de entero bacterias. La cepa de Klebsiella oxytoea fue sensible a 13 de los antibióticos estudiados, presentando una sensibilidad intermedia a piperacilina y siendo resistente a ticarcilina. Se realizaron encuestas alos veterinarios clínicos sobre los tratamientos que utilizaban para comparar nuestros resultados con la práctica clínica. Nuestros resultados apoyan la importancia de los ensayos de sensibilidad a antimicrobianos en las infeccionesen animales y sugieren que la gentamicina podría ser, en nuestra área, el antibiótico de elección para otitisexternas caninas crónicas causadas por enterobacterias

Dihydropyrimidine-thiones and clioquinol synergize to target beta-amyloid cellular pathologies through a metal-dependent mechanism

The lack of therapies for neurodegenerative diseases arises from our incomplete understanding of their underlying cellular toxicities and the limited number of predictive model systems. It is critical that we develop approaches to identify novel targets and lead compounds. Here, a phenotypic screen of yeast proteinopathy models identified dihydropyrimidine-thiones (DHPM-thiones) that selectively rescued the toxicity caused by β-amyloid (Aβ), the peptide implicated in Alzheimer’s disease. Rescue of Aβ toxicity by DHPM-thiones occurred through a metal-dependent mechanism of action. The bioactivity was distinct, however, from that of the 8-hydroxyquinoline clioquinol (CQ). These structurally dissimilar compounds strongly synergized at concentrations otherwise not competent to reduce toxicity. Cotreatment ameliorated Aβ toxicity by reducing Aβ levels and restoring functional vesicle trafficking. Notably, these low doses significantly reduced deleterious off-target effects caused by CQ on mitochondria at higher concentrations. Both single and combinatorial treatments also reduced death of neurons expressing Aβ in a nematode, indicating that DHPM-thiones target a conserved protective mechanism. Furthermore, this conserved activity suggests that expression of the Aβ peptide causes similar cellular pathologies from yeast to neurons. Our identification of a new cytoprotective scaffold that requires metal-binding underscores the critical role of metal phenomenology in mediating Aβ toxicity. Additionally, our findings demonstrate the valuable potential of synergistic compounds to enhance on-target activities, while mitigating deleterious off-target effects. The identification and prosecution of synergistic compounds could prove useful for developing AD therapeutics where combination therapies may be required to antagonize diverse pathologies.D.F.T was funded by NRSA Fellowship NIH 5F32NS061419. D.F.T. and S.L. were supported by WIBR funds in support of research on Regenerative Disease, the Picower/JPB Foundation, and the Edward N. and Della L. Thome Foundation. G.A.C. and S.L. were funded by a Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award. L.E.B., R.T., and S.E.S. were funded by NIH GM086180, NIH GM067041, and NIH GM111625. (5F32NS061419 - NRSA Fellowship NIH; WIBR funds in support of research on Regenerative Disease; Picower/JPB Foundation; Edward N. and Della L. Thome Foundation; Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award; GM086180 - NIH; NIH GM067041 - NIH; NIH GM111625 - NIH)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705239/Accepted manuscrip

New CRISPR Mutagenesis Strategies Reveal Variation in Repair Mechanisms among Fungi

We have created new vectors for clustered regularly interspaced short palindromic repeat (CRISPR) mutagenesis in Candida albicans, Saccharomyces cerevisiae, Candida glabrata, and Naumovozyma castellii These new vectors permit a comparison of the requirements for CRISPR mutagenesis in each of these species and reveal different dependencies for repair of the Cas9 double-stranded break. Both C. albicans and S. cerevisiae rely heavily on homology-directed repair, whereas C. glabrata and N. castellii use both homology-directed and nonhomologous end-joining pathways. The high efficiency of these vectors permits the creation of unmarked deletions in each of these species and the recycling of the dominant selection marker for serial mutagenesis in prototrophs. A further refinement, represented by the "Unified" Solo vectors, incorporates Cas9, guide RNA, and repair template into a single vector, thus enabling the creation of vector libraries for pooled screens. To facilitate the design of such libraries, we have identified guide sequences for each of these species with updated guide selection algorithms.IMPORTANCE CRISPR-mediated genome engineering technologies have revolutionized genetic studies in a wide range of organisms. Here we describe new vectors and guide sequences for CRISPR mutagenesis in the important human fungal pathogens C. albicans and C. glabrata, as well as in the related yeasts S. cerevisiae and N. castellii The design of these vectors enables efficient serial mutagenesis in each of these species by leaving few, if any, exogenous sequences in the genome. In addition, we describe strategies for the creation of unmarked deletions in each of these species and vector designs that permit the creation of vector libraries for pooled screens. These tools and strategies promise to advance genetic engineering of these medically and industrially important species.National Institutes of Health (U.S.) (Grant GM035010)National Institutes of Health (U.S.) (Grant GM118135)National Institutes of Health (U.S.) (Grant R15AI130950

Infraestructura tecnológica de servicios semánticos para la Web Semántica

This project aims at creating a network of distributed interoperable semantic services for building more complex ones. These services will be available in semantic Web service libraries, so that they can be invoked by other systems (e.g., semantic portals, software agents, etc.). Thus, to accomplish this objective, the project proposes: a) To create specific technology for developing and composing Semantic Web Services. b) To migrate the WebODE ontology development workbench to this new distributed interoperable semantic service architecture. c) To develop new semantic services (ontology learning, ontology mappings, incremental ontology evaluation, and ontology evolution). d) To develop technological support that eases semantic portal interoperability, using Web services and Semantic Web Services. The project results will be open source, so as to improve their technological transfer. The quality of these results is ensured by a benchmarking process. Keywords: Ontologies and Semantic We

PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal

Many acute and chronic anaemias, including haemolysis, sepsis and genetic bone marrow failure diseases such as Diamond–Blackfan anaemia, are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production. Treatment of these anaemias requires a drug that acts at an earlier stage of red cell formation and enhances the formation of Epo-sensitive CFU-E progenitors. Recently, we showed that glucocorticoids specifically stimulate self-renewal of an early erythroid progenitor, burst-forming unit erythroid (BFU-E), and increase the production of terminally differentiated erythroid cells. Here we show that activation of the peroxisome proliferator-activated receptor α (PPAR-α) by the PPAR-α agonists GW7647 and fenofibrate synergizes with the glucocorticoid receptor (GR) to promote BFU-E self-renewal. Over time these agonists greatly increase production of mature red blood cells in cultures of both mouse fetal liver BFU-Es and mobilized human adult CD34+ peripheral blood progenitors, with a new and effective culture system being used for the human cells that generates normal enucleated reticulocytes. Although Ppara−/− mice show no haematological difference from wild-type mice in both normal and phenylhydrazine (PHZ)-induced stress erythropoiesis, PPAR-α agonists facilitate recovery of wild-type but not Ppara−/− mice from PHZ-induced acute haemolytic anaemia. We also show that PPAR-α alleviates anaemia in a mouse model of chronic anaemia. Finally, both in control and corticosteroid-treated BFU-E cells, PPAR-α co-occupies many chromatin sites with GR; when activated by PPAR-α agonists, additional PPAR-α is recruited to GR-adjacent sites and presumably facilitates GR-dependent BFU-E self-renewal. Our discovery of the role of PPAR-α agonists in stimulating self-renewal of early erythroid progenitor cells suggests that the clinically tested PPAR-α agonists we used may improve the efficacy of corticosteroids in treating Epo-resistant anaemias.United States. Defense Advanced Research Projects Agency (Grant HR0011-14-2-0005)United States. Army Medical Research and Materiel Command (Grant W81WH-12-1-0449)National Heart, Lung, and Blood Institute (Grant 2 P01 HL032262-25

Evaluating synergy between marbofloxacin and gentamicin in Pseudomonas aeruginosa strains isolated from dogs with otitis externa

The aim of this study was to determine antimicrobial susceptibility of Pseudomonas aeruginosa strains to marbofloxacin and gentamicin, and investigate the possible synergistic, additive, indifferent or antagonistic effects between the two agents. P. aeruginosa strains can develop resistance quickly against certain antibiotics if used alone, thus the need emerges to find synergistic combinations. A total of 68 P. aeruginosa strains isolated from dogs were examined. In order to describe interactions between marbofloxacin and gentamicin the checkerboard microdilution method was utilized. The MICs (minimum inhibitory concentrations) for marbofloxacin and gentamicin were in the range 0.25–64 mg/L and 0.25–32 mg/L, respectively. The combination of marbofloxacin and gentamicin was more effective with a MIC range of 0.031–8 mg/L and a MIC90 of 1 mg/L, compared to 16 mg/L for marbofloxacin alone and 8 mg/L for gentamicin alone. The FIC (fractional inhibitory concentration) indices ranged from 0.0945 (pronounced synergy) to 1.0625 (indifference). Synergy between marbofloxacin and gentamicin was found in 33 isolates. The mean FIC index is 0.546, which represents a partial synergistic/additive effect close to the full synergy threshold. In vitro results indicate that marbofloxacin and gentamicin as partially synergistic agents may prove clinically useful in combination therapy against P. aeruginosa infections. Although marbofloxacin is not used in the human practice, the interactions between fluoroquinolones and aminoglycosides may have importance outside the veterinary field

A hybrid approach with agent-based simulation and clustering for sociograms

In the last years, some features of sociograms have proven to be strongly related to the performance of groups. However, the prediction of sociograms according to the features of individuals is still an open issue. In particular, the current approach presents a hybrid approach between agent-based simulation and clustering for simulating sociograms according to the psychological features of their members. This approach performs the clustering extracting certain types of individuals regarding their psychological characteristics, from training data. New people can then be associated with one of the types in order to run a sociogram simulation. This approach has been implemented with the tool called CLUS-SOCI (an agent-based and CLUStering tool for simulating SOCIograms). The current approach has been experienced with real data from four different secondary schools, with 38 real sociograms involving 714 students. Two thirds of these data were used for training the tool, while the remaining third was used for validating it. In the validation data, the resulting simulated sociograms were similar to the real ones in terms of cohesion, coherence of reciprocal relations and intensity, according to the binomial test with the correction of Bonferroni