Minimal Coverability Set for Petri Nets: Karp and Miller Algorithm with Pruning

This paper presents the Monotone-Pruning algorithm (MP) for computing the minimal coverability set of Petri nets. The original Karp and Miller algorithm (KM) unfolds the reachability graph of a Petri net and uses acceleration on branches to ensure termination. The MP algorithm improves the KM algorithm by adding pruning between branches of the tree. This idea was first introduced in the Minimal Coverability Tree algorithm (MCT), however it was recently shown to be incomplete. The MP algorithm can be viewed as the MCT algorithm with a slightly more aggressive pruning strategy which ensures completeness. Experimental results show that this algorithm is a strong improvement over the KM algorithm as it dramatically reduces the exploration tree

Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue

International audienceBackground: Dengue is the most widespread mosquito-borne viral disease of public health concern. In some patients, endothelial cell and platelet dysfunction lead to life-threatening hemorrhagic dengue fever or dengue shock syndrome. Prognostication of disease severity is urgently required to improve patient management. The pathogenesis of severe dengue has not been fully elucidated, and the role of host proteins associated with viral particles has received little exploration. Methods: The proteomes of virion-enriched fractions purified from plasma pools of patients with dengue fever or severe dengue were compared. Virions were purified by ultracentrifugation combined with a water-insoluble polyelectrolyte-based technique. Following in-gel hydrolysis, peptides were analyzed by nano-liquid chromatography coupled to ion trap mass spectrometry and identified using data libraries.Results: Both dengue fever and severe dengue viral-enriched fractions contained identifiable viral envelope proteins and host cellular proteins. Canonical pathway analysis revealed the identified host proteins are mainly involved in the coagulation cascade, complement pathway or acute phase response signaling pathway. Some host proteins were over- or under-represented in plasma from patients with severe dengue compared to patients with dengue fever. ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. Among 22 host proteins tested, two could differentiate between dengue fever and severe dengue in two independent cohorts (olfactomedin-4: area under the curve (AUC), 0.958; and platelet factor-4: AUC, 0.836).Conclusion: A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. The impact of these host proteins on pathogenicity and disease outcome are discussed

Additional file 4: of Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue

ELISA C1R and ceruloplasmin on DF of SD Cambodian plasma specimen. Results showed no significant difference between the two populations tested. (TIF 65 kb

Additional file 1: of Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue

Virus-enriched fraction proteome change in purified plasma pools obtained from acute dengue patients. (PDF 196 kb

Additional file 2: of Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue

Expression levels and relationship of the proteins identified by LC-MS/MS in the Acute Phase Response Signaling (2), the Complement system (3) and the Coagulation system (4). Diagrams have been obtained using the IPA software. Proteins are displayed by various shapes that represent the functional classes of proteins. Proteins in red correspond to proteins found over-represented in the SD pool. Proteins in green correspond to proteins found over-represented in the DF pool. Proteins in grey are only identified in the SD pool. The color intensity of each node is related to the level of expression. Uncolored node: no data available. (ZIP 815 kb

Additional file 3: of Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue

Network of the proteins identified by LC-MS/MS. The nature of the relationship between proteins is indicated by various line styles. Proteins are displayed by shapes that represent the functional classes of proteins. Proteins in red correspond to proteins found over-represented in the SD pool. Proteins in green correspond to proteins found over-represented in the DF pool. Proteins in grey are only identified in the SD pool. The color intensity of each node is related to the level of expression. (TIF 441 kb

Gene Expression Profiles in Alveolar Macrophages Induced by Lipopolysaccharide in Humans

Lipopolysaccharide (LPS) is ubiquitous in the environment. Inhalation of LPS has been implicated in the pathogenesis and/or severity of several lung diseases, including pneumonia, chronic obstructive pulmonary disease and asthma. Alveolar macrophages are the main resident leukocytes exposed to inhaled antigens. To obtain insight into which innate immune pathways become activated within human alveolar macrophages upon exposure to LPS in vivo, we conducted a study in eight healthy humans, in which we instilled sterile saline into a lung segment by bronchoscope, followed by instillation of LPS into the contralateral lung. Six hours later, a bilateral bronchoalveolar lavage was performed and whole-genome transcriptional profiling was done on purified alveolar macrophages, comparing cells exposed to saline or LPS from the same individuals. LPS induced differential expression of 2,932 genes in alveolar macrophages; 1,520 genes were upregulated, whereas 1,440 genes were downregulated. A total of 26 biological functions were overrepresented in LPS-exposed macrophages; 44 canonical pathways affected by LPS were identified, among which the genes associated with the role of pattern recognition receptors in recognition of bacteria and viruses represented the top pathway. Other pathways included cellular immune response, signaling by tumor necrosis factor (receptor) family members, cytokine signaling and glucocorticoid receptor signaling. These results reveal for the first time a large number of functional pathways influenced by the biologically relevant challenge provided by LPS administered into the airways. These data can assist in identifying novel targets for therapeutic intervention in pulmonary diseases associated with LPS exposure, including pneumonia, asthma and chronic obstructive pulmonary diseas

MOESM1 of Gene Expression Profiles in Alveolar Macrophages Induced by Lipopolysaccharide in Humans

Supplementary material, approximately 823 KB

Blood transcriptomics reveal the evolution and resolution of the immune response in tuberculosis

Blood transcriptomics have revealed major characteristics of the immune response in active TB, but the signature early after infection is unknown. In a unique clinically and temporally well-defined cohort of household contacts of active TB patients that progressed to TB, we define minimal changes in gene expression in incipient TB increasing in subclinical and clinical TB. While increasing with time, changes in gene expression were highest at 30 d before diagnosis, with heterogeneity in the response in household TB contacts and in a published cohort of TB progressors as they progressed to TB, at a bulk cohort level and in individual progressors. Blood signatures from patients before and during anti-TB treatment robustly monitored the treatment response distinguishing early and late responders. Blood transcriptomics thus reveal the evolution and resolution of the immune response in TB, which may help in clinical management of the disease