Semantic Matchmaking as Non-Monotonic Reasoning: A Description Logic Approach

Matchmaking arises when supply and demand meet in an electronic marketplace, or when agents search for a web service to perform some task, or even when recruiting agencies match curricula and job profiles. In such open environments, the objective of a matchmaking process is to discover best available offers to a given request. We address the problem of matchmaking from a knowledge representation perspective, with a formalization based on Description Logics. We devise Concept Abduction and Concept Contraction as non-monotonic inferences in Description Logics suitable for modeling matchmaking in a logical framework, and prove some related complexity results. We also present reasonable algorithms for semantic matchmaking based on the devised inferences, and prove that they obey to some commonsense properties. Finally, we report on the implementation of the proposed matchmaking framework, which has been used both as a mediator in e-marketplaces and for semantic web services discovery

PRICKLE1-related early onset epileptic encephalopathy

The PRICKLE1 (Prickle Planar Cell Polarity Protein 1-MIM 608500) gene is involved in different phases of human development. The related diseases include autosomal recessive progressive myoclonus epilepsy - ataxia syndrome, neural tube defects associated with heterozygous mutations, agenesis of corpus callosum, polymicrogyria, and autistic spectrum disorder. Reported here is a young boy with a new variant (NM_153026.2:c.820G>A, p.Ala274Thr) presenting with an early infantile epileptic encephalopathy with developmental arrest

The Human SLC25A33 and SLC25A36 Genes of Solute Carrier Family 25 Encode Two Mitochondrial Pyrimidine Nucleotide Transporters

The human genome encodes 53 members of the solute carrier family 25 (SLC25), also called the mitochondrial carrier family, many of which have been shown to transport inorganic anions, amino acids, carboxylates, nucleotides, and coenzymes across the inner mitochondrial membrane, thereby connecting cytosolic and matrix functions. Here two members of this family, SLC25A33 and SLC25A36, have been thoroughly characterized biochemically. These proteins were overexpressed in bacteria and reconstituted in phospholipid vesicles. Their transport properties and kinetic parameters demonstrate that SLC25A33 transports uracil, thymine, and cytosine (deoxy)nucleoside di- and triphosphates by an antiport mechanism and SLC25A36 cytosine and uracil (deoxy)nucleoside mono-, di-, and triphosphates by uniport and antiport. Both carriers also transported guanine but not adenine (deoxy)nucleotides. Transport catalyzed by both carriers was saturable and inhibited by mercurial compounds and other inhibitors of mitochondrial carriers to various degrees. In confirmation of their identity (i) SLC25A33 and SLC25A36 were found to be targeted to mitochondria and (ii) the phenotypes of Saccharomyces cerevisiae cells lacking RIM2, the gene encoding the well characterized yeast mitochondrial pyrimidine nucleotide carrier, were overcome by expressing SLC25A33 or SLC25A36 in these cells. The main physiological role of SLC25A33 and SLC25A36 is to import/export pyrimidine nucleotides into and from mitochondria, i.e. to accomplish transport steps essential for mitochondrial DNA and RNA synthesis and breakdown

Estudio análitico de resinas sintéticas : aisladas, mezcladas entre sí y mezcladas con resinas naturales

La gran variedad de resinas sintéticas obtenidas a partir de variostipos fundamentales y sus modificaciones, así como tambien su empleo en distintosgrados de polimerización, han creado un problema complejo para los químicosanalistas, sobre todo cuando se presentan en mezclas entre sí y con resinas naturales. Nuestro propósito ha sido, en base a la bibliografía más moderna sobreel tema, verificar hasta qué punto es posible resolver estos tipos de mezclas eidentificar sus componentes. Pasaremos por alto lo que se refiere a resinografíay técnicas espectrográficas, fuera de nuestro alcance, y también dejaremossin abordar el problema de los cauchos sintéticos, que algunos autores incluyenentre los plásticos. Se estudian en particular, las marchas analíticas propuestas por T.P. Gladstone Shaw, E. Fischer y técnicas o reacciones propuestas por otros autores. Se transcribe, en la primera parte de este trabajo, una clasificacióngeneral de las resinas naturales y sintéticas; sus características y aplicaciones. En la segunda parte, se desarrollan los métodos analíticos generalesy marchas propuestas para el exámen de estos productos.Fil: Di Noia, Ernesto M.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Evidence for Non-Essential Salt Bridges in the M-Gates of Mitochondrial Carrier Proteins

Mitochondrial carriers, which transport metabolites, nucleotides, and cofactors across the mitochondrial inner membrane, have six transmembrane α-helices enclosing a translocation pore with a central substrate binding site whose access is controlled by a cytoplasmic and a matrix gate (M-gate). The salt bridges formed by the three PX[DE]XX[RK] motifs located on the odd-numbered transmembrane α-helices greatly contribute to closing the M-gate. We have measured the transport rates of cysteine mutants of the charged residue positions in the PX[DE]XX[RK] motifs of the bovine oxoglutarate carrier, the yeast GTP/GDP carrier, and the yeast NAD+ transporter, which all lack one of these charged residues. Most single substitutions, including those of the non-charged and unpaired charged residues, completely inactivated transport. Double mutations of charged pairs showed that all three carriers contain salt bridges non-essential for activity. Two double substitutions of these non-essential charge pairs exhibited higher transport rates than their corre-sponding single mutants, whereas swapping the charged residues in these positions did not increase activity. The results demonstrate that some of the residues in the charged residue positions of the PX[DE]XX[KR] motifs are important for reasons other than forming salt bridges, probably for playing specific roles related to the substrate interaction-mediated conformational changes leading to the M-gate opening/closing

The Saccharomyces cerevisiae gene YPR011c encodes a mitochondrial transporter of adenosine 5'-phosphosulfate and 3'-phospho-adenosine 5'-phosphosulfate

The genome of Saccharomyces cerevisiae contains 35 members of the mitochondrial carrier family, nearly all of which have been functionally characterized. In this study, the identification of the mitochondrial carrier for adenosine 5'-phosphosulfate (APS) is described. The corresponding gene (YPR011c) was overexpressed in bacteria. The purified protein was reconstituted into phospholipid vesicles and its transport properties and kinetic parameters were characterized. It transported APS, 3'-phospho-adenosine 5'-phosphosulfate, sulfate and phosphate almost exclusively by a counter-exchange mechanism. Transport was saturable and inhibited by bongkrekic acid and other inhibitors. To investigate the physiological significance of this carrier in S. cerevisiae, mutants were subjected to thermal shock at 45°C in the presence of sulfate and in the absence of methionine. At 45°C cells lacking YPR011c, engineered cells (in which APS is produced only in mitochondria) and more so the latter cells, in which the exit of mitochondrial APS is prevented by the absence of YPR011cp, were less thermotolerant. Moreover, at the same temperature all these cells contained less methionine and total glutathione than wild-type cells. Our results show that S. cerevisiae mitochondria are equipped with a transporter for APS and that YPR011cp-mediated mitochondrial transport of APS occurs in S. cerevisiae under thermal stress condition

A yeast-based screening unravels potential therapeutic molecules for mitochondrial diseases associated with dominant ant1 mutations

Mitochondrial diseases result from inherited or spontaneous mutations in mitochondrial or nuclear DNA, leading to an impairment of the oxidative phosphorylation responsible for the synthesis of ATP. To date, there are no effective pharmacological therapies for these pathologies. We performed a yeast-based screening to search for therapeutic drugs to be used for treating mito-chondrial diseases associated with dominant mutations in the nuclear ANT1 gene, which encodes for the mitochondrial ADP/ATP carrier. Dominant ANT1 mutations are involved in several degen-erative mitochondrial pathologies characterized by the presence of multiple deletions or depletion of mitochondrial DNA in tissues of affected patients. Thanks to the presence in yeast of the AAC2 gene, orthologue of human ANT1, a yeast mutant strain carrying the M114P substitution equivalent to adPEO-associated L98P mutation was created. Five molecules were identified for their ability to suppress the defective respiratory growth phenotype of the haploid aac2M114P . Furthermore, these molecules rescued the mtDNA mutability in the heteroallelic AAC2/aac2M114P strain, which mimics the human heterozygous condition of adPEO patients. The drugs were effective in reducing mtDNA instability also in the heteroallelic strain carrying the R96H mutation equivalent to the more severe de novo dominant missense mutation R80H, suggesting a general therapeutic effect on diseases associated with dominant ANT1 mutations

Adherence and Constancy in LIME-RS Explanations for Recommendation

Explainable Recommendation has attracted a lot of attention due to a renewed interest in explainable artificial intelligence. In particular, post-hoc approaches have proved to be the most easily applicable ones to increasingly complex recommendation models, which are then treated as black boxes. The most recent literature has shown that for post-hoc explanations based on local surrogate models, there are problems related to the robustness of the approach itself. This consideration becomes even more relevant in human-related tasks like recommendation. The explanation also has the arduous task of enhancing increasingly relevant aspects of user experience such as transparency or trustworthiness. This paper aims to show how the characteristics of a classical post-hoc model based on surrogates is strongly model-dependent and does not prove to be accountable for the explanations generatedThe authors acknowledge partial support of PID2019-108965GB-I00, PONARS01_00876BIO-D,CasadelleTecnologie mergenti della Cittàdi Matera, PONARS01_00821FLET4.0, PIAServiziLocali2.0,H2020Passapartout-Grantn. 101016956, PIAERP4.0,andIPZS-PRJ4_IA_NORMATIV

MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils

The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a ‘homeologous' recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6−/− and Pms2−/− DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVλ GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of ‘homeologous' recombination insensitive to MM

Description Logics Approach to Semantic Matching of Web Services

As more resources and services become available on the Web, there is a growing need for infrastructures that, based on advertised descriptions, semantically match in a peer-to-peer way providers with requesters of web services. We address the problem of matchmaking of web services from a knowledge representation perspective. Based on our approach we propose match categorization in terms of exact match, potential match – when request and offer though not identical are compatible – and partial match – when one or more inconsistency is present – and rank of matches within categories. Then we report on our implementation of the proposed matchmaking framework in a prototype system