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

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

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

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

Novel population pharmacokinetic model for Linezolid in critically Ill patients and evaluation of the adequacy of the current dosing recommendation

Antimicrobial treatment in critically ill patients remains challenging. The aim of this study was to develop a population pharmacokinetic model for linezolid in critically ill patients and to evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and effluent samples were drawn after linezolid administration at defined time points, and linezolid levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3. The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated (AUC24/MIC > 80 and 100% T>MIC). A two-compartment model best described the pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose of linezolid did not cover infections caused by pathogens with MIC ≥ 2 mg/L. Continuous infusion may be an alternative, especially when renal function is preserved

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

Estimating the completeness of AIDS reporting in Spain

[ES] ObjetivoValorar la notificación de casos de sida en las comunidades autónomas por comparación con las muertes por sida registradas en las estadísticas de defunciones, a fin de identificar posibles desviaciones indicativas de subnotificación. MétodosTomando como unidad de análisis la comunidad autónoma, se compararon las tasas de incidencia y mortalidad, según el Registro Nacional de Sida, con las de mortalidad por VIH y sida obtenidas de las estadísticas de defunciones del Instituto Nacional de Estadística. Se analizó globalmente el período 1986–1998, y se repitió el análisis para el período 1995–1998. ResultadosEn el período 1986-1998 hubo una buena correlación (r = 0,93) entre las tasas de incidencia de sida y las de mortalidad por VIH/sida según las estadísticas de defunciones. Algunas comunidades presentaron una incidencia de sida menor que la esperada por su tasa de mortalidad en comparación con el promedio estatal, destacando Asturias (–27%), la Comunidad Valenciana (–26%), Andalucía (–20%), Ceuta (–18%) y Cantabria (–13%). Tomando como referencia las cinco comunidades con mayor exhaustividad, la subnotificación estimada para el conjunto de España fue del 13%. En el período 1995–1998 estas desviaciones han aumentado moderadamente. En el período 1986–1998 se notificaron un 18,9% menos de muertes al Registro Nacional de Sida que a la estadística de defunciones, con una gran variabilidad entre comunidades. Conclusiones El nivel de notificación de sida en España es aceptable para los fines de la vigilancia epidemiológica, aunque en algunas comunidades deberían tomarse medidas para mejorarlo. La notificación de fallecimientos al registro de sida presenta grandes deficiencias. [EN] Objective To evaluate AIDS case reporting in the Spanish regions as compared with the AIDS deaths registered in mortality statistics, in order to identify possible deviations indicative of underreporting. Methods. We carried out an ecological analysis taking each region as a unit. We compared incidence and mortality obtained from the AIDS reporting system with the HIV/AIDS deaths obtained from the mortality statistics of the Spanish Institute for Statistics. The 1986–1998 period was analysed globally, then the analysis was repeated for the 1995–1998 period. Results In the 1986–1998 period there was a good correlation (r = 0.93) between the AIDS incidence rates and HIV/AIDS mortality rates obtained from death statistics. Some regions presented an AIDS incidence lower than expected according to their mortality rate when it was compared with the national average, with Asturias (–27%), Comunidad Valenciana (–26%), Andalucia (–20%), Ceuta (–18%) and Cantabria (–13%) standing out. Taking as a reference the five regions with the highest completeness, the underreporting in Spain was of 13%. In the 1995–1998 period these deviations increased moderately. In the 1986–1998 period, 18.9% less deaths were notified to the AIDS reporting system in comparison with death statistics, showing a great variability between regions. Conclusions In Spain the reporting level of AIDS cases is acceptable for the aims of surveillance, although in some regions measures to improve it should be taken. The notification of deaths to the AIDS reporting system presents great deficiencies.S

The C. elegans Snail homolog CES-1 can activate gene expression in vivo and share targets with bHLH transcription factors

Snail-type transcription factors (TFs) are found in numerous metazoan organisms and function in a plethora of cellular and developmental processes including mesoderm and neuronal development, apoptosis and cancer. So far, Snail-type TFs are exclusively known as transcriptional repressors. They repress gene expression by recruiting transcriptional co-repressors and/or by preventing DNA binding of activators from the basic helix-loop-helix (bHLH) family of TFs to CAGGTG E-box sequences. Here we report that the Caenorhabditis elegans Snail-type TF CES-1 can activate transcription in vivo. Moreover, we provide results that suggest that CES-1 can share its binding site with bHLH TFs, in different tissues, rather than only occluding bHLH DNA binding. Together, our data indicate that there are at least two types of CES-1 target genes and, therefore, that the molecular function of Snail-type TFs is more plastic than previously appreciated