The KB paradigm and its application to interactive configuration

The knowledge base paradigm aims to express domain knowledge in a rich formal language, and to use this domain knowledge as a knowledge base to solve various problems and tasks that arise in the domain by applying multiple forms of inference. As such, the paradigm applies a strict separation of concerns between information and problem solving. In this paper, we analyze the principles and feasibility of the knowledge base paradigm in the context of an important class of applications: interactive configuration problems. In interactive configuration problems, a configuration of interrelated objects under constraints is searched, where the system assists the user in reaching an intended configuration. It is widely recognized in industry that good software solutions for these problems are very difficult to develop. We investigate such problems from the perspective of the KB paradigm. We show that multiple functionalities in this domain can be achieved by applying different forms of logical inferences on a formal specification of the configuration domain. We report on a proof of concept of this approach in a real-life application with a banking company. To appear in Theory and Practice of Logic Programming (TPLP).Comment: To appear in Theory and Practice of Logic Programming (TPLP

Identification and inhibition of carbonic anhydrases from nematodes.

Carbonic anhydrases (CAs) are metalloenzymes, and classified into the evolutionarily distinct α, β, γ, δ, ζ, and η classes. α-CAs are present in many living organisms. β- and γ-CAs are expressed in most prokaryotes and eukaryotes, except for vertebrates. δ- and ζ-CAs are present in phytoplanktons, and η-CAs have been found in Plasmodium spp. Since the identification of α- and β-CAs in Caenorhabditis elegans, the nematode CAs have been considered as an emerging target in research focused on antiparasitic CA inhibitors. Despite the presence of α-CAs in both helminths and vertebrates, structural studies have revealed different kinetic and inhibition results. Moreover, lack of β-CAs in vertebrates makes this enzyme as an attractive target for inhibitory studies against helminthic infection. Some CA inhibitors, such as sulfonamides, have been evaluated against nematode CAs. This review article aims to present comprehensive information about the nematode CAs and their inhibitors as potential anthelminthic drugs

One More Decidable Class of Finitely Ground Programs

Abstract. When a logic program is processed by an answer set solver, the first task is to generate its instantiation. In a recent paper, Calimeri et el. made the idea of efficient instantiation precise for the case of disjunctive programs with function symbols, and introduced the class of “finitely ground ” programs that can be efficiently instantiated. Since that class is undecidable, it is important to find its large decidable subsets. In this paper, we introduce such a subset—the class of argument-restricted programs. It includes, in particular, all finite domain programs, ω-restricted programs, and λ-restricted programs.

HLA-G Alleles Impact the Perinatal Father–Child HPV Transmission

The host factors that influence father-to-child human papillomavirus (HPV) transmission remain unknown. This study evaluated whether human leukocyte antigen (HLA)-G alleles are important in father-to-child HPV transmission during the perinatal period. Altogether, 134 father–newborn pairs from the Finnish Family HPV Study were included. Oral, semen and urethral samples from the fathers were collected before the delivery, and oral samples were collected from their offspring at delivery and postpartum on day 3 and during 1-, 2- and 6-month follow-up visits. HLA-G alleles were tested by direct sequencing. Unconditional logistic regression was used to determine the association of the father–child HLA-G allele and genotype concordance with the father–child HPV prevalence and concordance at birth and during follow-up. HLA-G allele G*01:01:03 concordance was associated with the father’s urethral and child’s oral high-risk (HR)-HPV concordance at birth (OR 17.00, 95% CI: 1.24–232.22). HLA-G allele G*01:04:01 concordance increased the father’s oral and child’s postpartum oral any- and HR-HPV concordance with an OR value of 7.50 (95% CI: 1.47–38.16) and OR value of 7.78 (95% CI: 1.38–43.85), respectively. There was no association between different HLA-G genotypes and HPV concordance among the father–child pairs at birth or postpartum. To conclude, the HLA-G allele concordance appears to impact the HPV transmission between the father and his offspring.Peer reviewe

beta carbonic anhydrase is required for female fertility in Drosophila melanogaster

Background: Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous enzymes that catalyze the reversible hydration reaction of carbon dioxide. CAs are present as six structurally divergent enzyme families: alpha, beta, gamma, delta, zeta and eta. beta-CAs have a wide distribution across different species including invertebrates. Previously, we showed that Drosophila melanogaster beta-CA is a highly active mitochondrial enzyme. In this study, we investigated the function of Drosophila beta-CA by silencing the expression of the beta-CA gene using UAS/GAL4-based RNA interference (RNAi) in Drosophila in vivo. Results: Crossing beta-CA RNAi lines over ubiquitous Actin driver flies did not produce any viable progeny, indicating that beta-CA expression is required for fly development. RNAi silencing of beta-CA ubiquitously in adult flies did not affect their survival rate or function of mitochondrial electron transport chain. Importantly, beta-CA RNAi led to impaired reproduction. All beta-CA knockdown females were sterile, and produced few or no eggs. Whole ovaries of knockdown females looked normal but upon cadherin staining, there was an apparent functional defect in migration of border cells, which are considered essential for normal fertilization. Conclusions: These results indicate that although Drosophila beta-CA is dispensable for survival of adult flies, it is essential for female fertility.Peer reviewe

Characterization of the first beta-class carbonic anhydrase from an arthropod (Drosophila melanogaster) and phylogenetic analysis of beta-class carbonic anhydrases in invertebrates

BACKGROUND: The beta-carbonic anhydrase (CA, EC 4.2.1.1) enzymes have been reported in a variety of organisms, but their existence in animals has been unclear. The purpose of the present study was to perform extensive sequence analysis to show that the beta-CAs are present in invertebrates and to clone and characterize a member of this enzyme family from a representative model organism of the animal kingdom, e.g., Drosophila melanogaster. RESULTS: The novel beta-CA gene, here named DmBCA, was identified from FlyBase, and its orthologs were searched and reconstructed from sequence databases, confirming the presence of beta-CA sequences in 55 metazoan species. The corresponding recombinant enzyme was produced in Sf9 insect cells, purified, kinetically characterized, and its inhibition was investigated with a series of simple, inorganic anions. Holoenzyme molecular mass was defined by dynamic light scattering analysis and gel filtration, and the results suggested that the holoenzyme is a dimer. Double immunostaining confirmed predictions based on sequence analysis and localized DmBCA protein to mitochondria. The enzyme showed high CO2 hydratase activity, with a kcat of 9.5 x 105 s-1 and a kcat/KM of 1.1 x 108 M-1s-1. DmBCA was appreciably inhibited by the clinically-used sulfonamide acetazolamide, with an inhibition constant of 49 nM. It was moderately inhibited by halides, pseudohalides, hydrogen sulfide, bisulfite and sulfate (KI values of 0.67 - 1.36 mM) and more potently by sulfamide (KI of 0.15 mM). Bicarbonate, nitrate, nitrite and phenylarsonic/boronic acids were much weaker inhibitors (KIs of 26.9 - 43.7 mM). CONCLUSIONS: The Drosophila beta-CA represents a highly active mitochondrial enzyme that is a potential model enzyme for anti-parasitic drug development

The association of HLA-G polymorphism with oral and genital HPV infection in men

The host genetic factors that influence the natural history of human papillomavirus (HPV) infection in men are not well known. Our aim was to evaluate the role of human leukocyte antigen (HLA)-G polymorphism in oral and genital HPV infection in men. Altogether, 130 men from the Finnish Family HPV Study, with a 6-year follow-up, were included in the analyses. HLA-G alleles were tested by direct sequencing. Oral, urethral, and semen samples were collected and analyzed for 24 different HPV genotypes. Unconditional logistic regression was used to determine associations between HLA-G alleles and genotypes with HPV infection and its outcomes. Overall, eight different HLA-G alleles were identified with 15 different HLA-G genotype combinations. The most common HLA-G allele among the men was G*01:01:01 (86.2%, n = 112) followed by G*01:01:02 (36.2%, n = 47). Allele G*01:01:02 showed to be protective against any- and high-risk (HR) oral HPV (OR range of 0.20-0.24, 95% CI range of 0.06-0.85). Men having allele G*01:01:01 showed a reduced risk for incident (OR 0.30, 95% CI 0.11-0.84) and persistent (OR 0.24, 95% CI 0.08-0.69) oral infections. Allele G*01:01:03 was associated with increased risk for urethral HR-HPV infections (OR 4.94, 95% CI 1.34-18.27). Among self-reported demographic data, genotype G*01:01:01/01:01:03 was associated with an increased risk for oral warts (OR 8.00, 95% CI 1.23-51.89) and allele G*01:03:01 increased the risk of pollen and/or animal allergy (OR 13.59, 95% CI 1.57-117.25). To conclude, HLA-G polymorphism in men largely impacts the outcome of an oral HPV infection and seems to associate with self-reported allergies.Peer reviewe

The association of HLA-G polymorphism with oral and genital HPV infection in men

The host genetic factors that influence the natural history of human papillomavirus (HPV) infection in men are not well known. Our aim was to evaluate the role of human leukocyte antigen (HLA)-G polymorphism in oral and genital HPV infection in men. Altogether, 130 men from the Finnish Family HPV Study, with a 6-year follow-up, were included in the analyses. HLA-G alleles were tested by direct sequencing. Oral, urethral, and semen samples were collected and analyzed for 24 different HPV genotypes. Unconditional logistic regression was used to determine associations between HLA-G alleles and genotypes with HPV infection and its outcomes. Overall, eight different HLA-G alleles were identified with 15 different HLA-G genotype combinations. The most common HLA-G allele among the men was G*01:01:01 (86.2%, n = 112) followed by G*01:01:02 (36.2%, n = 47). Allele G*01:01:02 showed to be protective against any- and high-risk (HR) oral HPV (OR range of 0.20-0.24, 95% CI range of 0.06-0.85). Men having allele G*01:01:01 showed a reduced risk for incident (OR 0.30, 95% CI 0.11-0.84) and persistent (OR 0.24, 95% CI 0.08-0.69) oral infections. Allele G*01:01:03 was associated with increased risk for urethral HR-HPV infections (OR 4.94, 95% CI 1.34-18.27). Among self-reported demographic data, genotype G*01:01:01/01:01:03 was associated with an increased risk for oral warts (OR 8.00, 95% CI 1.23-51.89) and allele G*01:03:01 increased the risk of pollen and/or animal allergy (OR 13.59, 95% CI 1.57-117.25). To conclude, HLA-G polymorphism in men largely impacts the outcome of an oral HPV infection and seems to associate with self-reported allergies