Regression models with MoPs Bayesian networks

We present a model of Bayesian network for continuous variables, where densities and conditional densities are estimated with B-spline MoPs. We use a novel approach to directly obtain conditional densities estimation using B-spline properties. In particular we implement naive Bayes and wrapper variables selection. Finally we apply our techniques to the problem of predicting neurons morphological variables from electrophysiological ones.

Expressive power of binary relevance and chain classifiers based on Bayesian Networks for multi-label classification

Bayesian network classifiers are widely used in machine learning because they intuitively represent causal relations. Multi-label classification problems require each instance to be assigned a subset of a defined set of h labels. This problem is equivalent to finding a multi-valued decision function that predicts a vector of h binary classes. In this paper we obtain the decision boundaries of two widely used Bayesian network approaches for building multi-label classifiers: Multi-label Bayesian network classifiers built using the binary relevance method and Bayesian network chain classifiers. We extend our previous single-label results to multi-label chain classifiers, and we prove that, as expected, chain classifiers provide a more expressive model than the binary relevance method.

Neuronanatomy, neurology and Bayesian networks

Bayesian networks are data mining models with clear semantics and a sound theoretical foundation. In this keynote talk we will pinpoint a number of neuroscience problems that can be addressed using Bayesian networks. In neuroanatomy, we will show computer simulation models of dendritic trees and classification of neuron types, both based on morphological features. In neurology, we will present the search for genetic biomarkers in Alzheimer's disease and the prediction of health-related quality of life in Parkinson's disease. Most of these challenging problems posed by neuroscience involve new Bayesian network designs that can cope with multiple class variables, small sample sizes, or labels annotated by several experts.

Colonización bacteriana y oxidación de aceros inoxidables austeníticos, ferríticos y dúplex sinterizados

Las características y capacidades de los aceros inoxidables sinterizados se han investigado en una doble vertiente. Por una parte con vista a sus capacidades de resistencia a la oxidación en caliente y por otra parte se ha investigado su capacidad para retener microorganismos que contribuyan a la descontaminación de un ambiente. Por ello, para cada una de estas funciones se han utilizado los aceros inoxidables sinterizados, que se han considerado más adecuados. Para estudiar sus capacidades de resistencia a la oxidación en caliente se ha utilizado un acero inoxidable austenítico AISI 304L, un acero inoxidable ferrítico AISI 430L y un acero inoxidable Fe-16Cr-3Al. Para estudiar sus capacidades para retener microorganismos se ha utilizado un acero inoxidable austenítico AISI 316L, un acero inoxidable ferrítico AISI 430L y un acero inoxidable dúplex 50%/50% de los anteriores. Para esta última finalidad los aceros se han compactado a tres diferentes presiones 300, 500 y 700 MPa, a las que corresponden diferentes porosidades. En relación con el comportamiento frente a la oxidación en caliente, se han cuantificado los incrementos positivos o negativos de volumen, masa y densidad en los diferentes tipos de sinterización y estados de tratamiento de oxidación. Como tónica general de comportamiento, puede decirse que los aceros sinterizados bajo vacío son más resistentes a la oxidación, que los sinterizados en atmósfera de N2-5H2 y que los aceros inoxidables austeníticos son algo más resistentes, que los Cr-Al y estos, a su vez, más que los aceros inoxidables ferríticos. Respecto a la retención de microorganismos, los tres aceros inoxidables sinterizados se han ensayado en diferentes medios de cultivo, utilizando cuatro especies de bacterias. Los mejores resultados se han obtenido con Staphylococcus aureus, muy favorable para su observación y recuento. Se han cuantificado, una vez sinterizados y colonizados por los microorganismos, para cada material y presión de compactación, las áreas de cada uno de los poros y el número de microorganismos situados en los poros y en la superficie sin poros. Se ha establecido en cada caso la densidad de microorganismos en las zonas de poros y en las zonas sin poros. Como tónica general puede decirse, que los aceros inoxidables austeníticos aparecen más favorables para estos estudios, que los aceros dúplex y estos más que los inoxidables ferríticos. Asimismo, se desprende que las áreas de los poros dependen de forma unívoca de la presión de compactación y que para áreas de poros decrecientes las densidades de microorganismos son crecientes. En consecuencia, podría deducirse, que a igualdad de área de poros en una superficie, aquella que tuviera los poros más pequeños, retendría mayor cantidad de bacterias. ABSTRACT The characteristics and capacities of sintered stainless steels have been researched from two perspectives: firstly, with a view to their resistance to hot oxidation, and secondly their capacity to retain microorganisms able to decontaminate the environment. For both these functions, sintered stainless steels were used, which are considered to be the most fit for purpose. To study their resistance to hot oxidation, we used austenitic stainless steel AISI 304L, ferritic stainless steel AISI 430L and stainless steel Fe-16Cr-3Al. To study their ability to retain microorganisms, we used austenitic stainless steel AISI 316L, ferritic stainless steel AISI 430L, and duplex stainless steel, being a 50/50 blend of the two former ones. For this last purpose, the steels were compacted at three different pressures (300, 500 and 700 MPa) corresponding to different porosities. With regard to the hot oxidation, we quantified the positive or negative increments in volume, mass and density in the different types of sintering and oxidation treatment states. As a general performance trend, we observed that vacuum sintered steels are more resistant to oxidation than those sintered in an atmosphere of N2-5H2, and that austenitic stainless steels are slightly more resistant than the Cr-Al steels which, in turn, are more resistant than the ferritic stainless steels. With regard to the retention of microorganisms, the three sintered stainless steels were tested in different culture media using four types of bacteria. The best results for observation and counting were obtained with Staphylococcus aureus bacteria. Once sintered and colonized by microorganisms, for each material and compacting pressure we quantified the areas of the pores and the number of microorganisms situated in the pores and on the pore-free surface. In each case, the density of microorganisms in the pores and in the pore-free areas was established. As a general rule, we can say that the austenitic stainless steels appear to be more favourable for this type of study than the duplex steels which, in turn, are more favourable than the ferritic stainless steels. It also emerged that the areas with the pores depend unequivocally on the compacting pressure, and that the smaller the area of the pore the higher the density of the microorganisms. Consequently, it can be deduced that comparing an equal area of pores on a surface, the one with the smaller pores would retain a larger number of bacteria.

Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis.

Due to the resurgence of tuberculosis and the emergence of multidrug-resistant strains, fluoroquinolones (FQ) are being used in selected tuberculosis patients, but FQ-resistant strains of Mycobacterium tuberculosis have rapidly begun to appear. The mechanisms involved in FQ resistance need to be elucidated if the effectiveness of this class of antibiotics is to be improved and prolonged. By using the rapid-growing Mycobacterium smegmatis as a model genetic system, a gene was selected that confers low-level FQ resistance when present on a multicopy plasmid. This gene, lfrA, encodes a putative membrane efflux pump of the major facilitator family, which appears to recognize the hydrophilic FQ, ethidium bromide, acridine, and some quaternary ammonium compounds. It is homologous to qacA from Staphylococcus aureus, tcmA, of Streptomyces glaucescens, and actII and mmr, both from Streptomyces coelicoler. Increased expression of lfrA augments the appearance of subsequent mutations to higher-level FQ resistance.

Novel microbicidal agents derived from Naja atra cardiotoxin 1 (CTX-1)

During my PhD course, I focused my research on antimicrobial peptides (AMPs), in particular on the aspects of their computational design and development. This work led to the development of a new family of AMPs that I designed, starting from the amino acid sequence of a snake venom toxin, the cardiotoxin 1 (CTX-1) of Naja atra. Naja atra atra cardiotoxin 1, produced by Chinese cobra snakes belonging to Elapidae family, is included in the three-finger toxin family and exerts high cytotoxicity and antimicrobial activity too. This toxin family is characterized by specific folding of three beta-sheet loops (“fingers”) extending from the central core and by four conserved disulfide bridges. Using as template the first loop of this toxin, different sequences of 20 amino acids linear cationic peptides have been designed in order to avoid toxic effects but to maintain and strengthen the antimicrobial activity. As a result, the sequence NCP-0 (Naja Cardiotoxin Peptide-0) was designed as ancestor and subsequently other 4 variant sequences of NCP0 were developed. These variant sequences have shown microbicidal activity towards a panel of reference strains of Gram-positive and Gram-negative bacteria, fungi and an enveloped virus. In particular, the sequence designed as NCP-3 (Naja Cardiotoxin Peptide-3) and its variants NCP-3a and NCP-3b have shown the best antimicrobial activity together with low cytotoxicity against eukaryotic cells and low hemolytic activity. Bactericidal activity has been demonstrated by minimum bactericidal concentration (MBC) assay at values below 10 μg/ml for Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii ( clinical isolates), Moraxella catharralis ATCC 25238, MRSA ATCC 43400, while towards Staphylococcus aureus ATCC 25923, Enterococcus hirae ATCC 10541 and Streptococcus agalactiae ATCC 13813 the bactericidal activity was demonstrated even below 1.6 μg/ml concentration. This potent antimicrobial activity was confirmed even for unicellular fungi Candida albicans, Candida glabrata and Malassezia pachydermatis (MBC 32.26-6.4 μg/ml), and also against the fast-growing mycobacteria Mycobacterium smegmatis DSMZ 43756 and Mycobacterium fortuitum DSMZ 46621 (MBC 100 μg/ml). Moreover, NCP-3 has shown a virucidal activity on the enveloped virus Bovine Herpesvirus 1 (BoHV1) belonging to herpesviridae family. The bactericidal activity is maintained in a high salt concentration (125 and 250 mM NaCl) medium and PB +20% Mueller Hinton Medium for E. coli, MRSA and Pseudomonas aeruginosa reference strains. Considering these in vitro obtained data, we propose NCP-3 and its variants NCP-3a and NCP-3b as promising antimicrobial candidates. For this reason, the whole novel AMPs family has been protected by a national patent (n°102015000015951).