Integrating Systems around the User: Combining Isabelle, Maple, and QEPCAD in the Prover's Palette

AbstractWe describe the Proverʼs Palette, a general, modular architecture for combining tools for formal verification, with the key differentiator that the integration emphasises the role of the user. A concrete implementation combining the theorem prover Isabelle with the computer algebra systems Maple and QEPCAD-B is then presented. This illustrates that the design principles of the Proverʼs Palette simplify tool integrations while enhancing the power and usability of theorem provers

Full-Length L1CAM and Not Its Δ2Δ27 Splice Variant Promotes Metastasis through Induction of Gelatinase Expression

Tumour-specific splicing is known to contribute to cancer progression. In the case of the L1 cell adhesion molecule (L1CAM), which is expressed in many human tumours and often linked to bad prognosis, alternative splicing results in a full-length form (FL-L1CAM) and a splice variant lacking exons 2 and 27 (SV-L1CAM). It has not been elucidated so far whether SV-L1CAM, classically considered as tumour-associated, or whether FL-L1CAM is the metastasis-promoting isoform. Here, we show that both variants were expressed in human ovarian carcinoma and that exposure of tumour cells to pro-metastatic factors led to an exclusive increase of FL-L1CAM expression. Selective overexpression of one isoform in different tumour cells revealed that only FL-L1CAM promoted experimental lung and/or liver metastasis in mice. In addition, metastasis formation upon up-regulation of FL-L1CAM correlated with increased invasive potential and elevated Matrix metalloproteinase (MMP)-2 and -9 expression and activity in vitro as well as enhanced gelatinolytic activity in vivo. In conclusion, we identified FL-L1CAM as the metastasis-promoting isoform, thereby exemplifying that high expression of a so-called tumour-associated variant, here SV-L1CAM, is not per se equivalent to a decisive role of this isoform in tumour progression

Bacterial Signatures of Paediatric Respiratory Disease : An Individual Participant Data Meta-Analysis

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies.Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses.Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively.Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.Peer reviewe

Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention

© 2016 International Society for Microbial Ecology All rights reserved. Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression. In this study multiple sputum samples were collected from adult CF patients over the course of CFPEs to better understand how changes in microbiota are associated with CFPE onset and management. Data were divided into five clinical periods: pre-CFPE baseline, CFPE, antibiotic treatment, recovery, and post-CFPE baseline. Samples were treated with propidium monoazide prior to DNA extraction, to remove the impact of bacterial cell death artefacts following antibiotic treatment, and then characterised by 16S rRNA gene-targeted high-throughput sequencing. Partitioning CF microbiota into core and rare groups revealed compositional resistance to CFPE and resilience to antibiotics interventions. Mixed effects modelling of core microbiota members revealed no significant negative impact on the relative abundance of Pseudomonas aeruginosa across the exacerbation cycle. Our findings have implications for current CFPE management strategies, supporting reassessment of existing antimicrobial treatment regimens, as antimicrobial resistance by pathogens and other members of the microbiota may be significant contributing factors

Petróleo y producción agropecuaria en las relaciones bilaterales entre Colombia y Venezuela

Las relaciones bilaterales entre Colombia y Venezuela se caracterizan por una interdependencia de tipo estructural dada por el petróleo como factor vinculante. La industria petrolera venezolana deterioro a tal punto su sector agropecuario, que puso en riesgo la seguridad alimentaria de los venezolanos, hecho que hace a Venezuela depender de los productos agropecuarios colombianos y a su vez, que la producción agropecuaria colombiana se enfoque a entender este mercado en Venezuela

Inventario micobi�tico de la regi�n de Tapalpa, Jalisco, M�xico

Se presentan 233 taxa (especies y variedades) de hongos (229 macromicetes y cuatro micromicetes) de la regi�n de Tapalpa, Jalisco. El material estudiado fue recolectado en los a�os 2000 al 2003, principalmente en bosques de Pinus y Quercus. Se examinaron adem�s otros ejemplares depositados en el Herbario IBUG provenientes de dicha �rea. Se registran por primera vez de Jalisco 21 taxa. Doscientos cinco especies (88%) pertenecen a Basidiomycota, 22 (9.5%) a Ascomycota y 6 (2.5%) a Myxomycota. �ste constituye el primer inventario micol�gico de la zona