Constraint-based sequence mining using constraint programming

The goal of constraint-based sequence mining is to find sequences of symbols that are included in a large number of input sequences and that satisfy some constraints specified by the user. Many constraints have been proposed in the literature, but a general framework is still missing. We investigate the use of constraint programming as general framework for this task. We first identify four categories of constraints that are applicable to sequence mining. We then propose two constraint programming formulations. The first formulation introduces a new global constraint called exists-embedding. This formulation is the most efficient but does not support one type of constraint. To support such constraints, we develop a second formulation that is more general but incurs more overhead. Both formulations can use the projected database technique used in specialised algorithms. Experiments demonstrate the flexibility towards constraint-based settings and compare the approach to existing methods.Comment: In Integration of AI and OR Techniques in Constraint Programming (CPAIOR), 201

Comparative evaluation of pyrethroid insecticide formulations against Triatoma infestans (Klug): residual efficacy on four substrates

We investigated the residual efficacy of four insecticide formulations used in Chagas disease vector control campaigns: cyfluthrin 12.5% suspension concentrace (SC), lambda- cyhalothrin 10% wettable powder (WP), deltamethrin 2.5% SC, and 2.5% WP on four types of circular blocks of wood, straw with mud, straw with mud painted with lime, and mud containing 5% of cement. Three concentrations of these insecticides were tested: the LC90 (previously determined on filter paper), the double of the LC90, and the recommended operational dose. For each bioassay test, 15 third-stage nymphs of Triatoma infestans (Klug) (Hemiptera: Reduviidae) were exposed for 120 h to each treatment at 24 h, 30, 60, 90, and 180 days post-spraying. Mortality rates, moulting history and behaviour were recorded at 24, 48, 72, and 120 h of exposure. Mortality rates were highest during the first 30 days post-spraying. Highest mortality rates (above 50%) were observed for deltamethrin 2.5% SC and lambda-cyhalothrin 10% WP on wood blocks up to three months post-spraying. Mud was the substrate on which treatments showed lowest persistence, with the other two substrates showing intermediate residual efficacy of all treatments. During the first 30 days WP formulations were not as effective as SC flowable formulations but, overall in the longer term, WP gave grater mortality rates of T. infestans nymphs exposed at up to six months post-spraying. Porous surfaces, especially mud, showed most variability presumably due to absorption of the insecticide. In contrast the less porous surfaces (i.e. wood and lime-coated mud) kept mortality rates high for longer post-treatment, irrespective of the insecticide concentration used

Developing a coding scheme for analysing classroom dialogue across educational contexts

The research reported sought to develop a framework for systematically analysing classroom dialogue for application across a range of educational settings. The paper outlines the development and refinement of a coding scheme that attempts to represent and operationalise commonalities amongst some key theorists in the field concerning productive forms of educational dialogue. The team has tested it using video recordings from classroom settings in the UK and Mexico, across age phases, subject areas, and different interactional contexts including whole class, group and paired work. Our Scheme for Educational Dialogue Analysis (SEDA) is situated within a sociocultural paradigm, and draws on Hymes' Ethnography of Communication to highlight the importance of context. We examined how such a tool could be used in practice. We found that concentrating on the ‘communicative act’ to explore dialogue between participants was an appropriate level of granularity, while clustering the 33 resulting codes according to function of the acts helped to highlight dialogic sequences within lessons. We report on the application of the scheme in two different learning contexts and reflect on its fitness for purpose, including perceived limitations. Development of specialised sub-schemes and a version for teachers is underway

Developing a coding scheme for analysing classroom dialogue across d educational contexts.

The research reported sought to develop a framework for systematically analysing classroom dialogue for application across a range of educational settings. The paper outlines the development and refinement of a coding scheme that attempts to represent and operationalise commonalities amongst some key theorists in the field concerning productive forms of educational dialogue. The team has tested it using video recordings from classroom settings in the UK and Mexico, across age phases, subject areas, and different interactional contexts including whole class, group and paired work. Our Scheme for Educational Dialogue Analysis (SEDA) is situated within a sociocultural paradigm, and draws on Hymes' Ethnography of Communication to highlight the importance of context. We examined how such a tool could be used in practice. We found that concentrating on the ‘communicative act’ to explore dialogue between participants was an appropriate level of granularity, while clustering the 33 resulting codes according to function of the acts helped to highlight dialogic sequences within lessons. We report on the application of the scheme in two different learning contexts and reflect on its fitness for purpose, including perceived limitations. Development of specialised sub-schemes and a version for teachers is underway.This collaborative work was carried out for a project entitled “A Tool for Analysing Dialogic Interactions in Classrooms” (http://tinyurl.com/BAdialogue) funded through the British Academy International Partnership and Mobility Scheme (ref. RG66509), between January 2013 - December 2015. We are most grateful to colleagues on the project teams who made significant contributions and helpful input during development and testing of the scheme and preparation of the manuscript, including Farah Ahmed, Riikka Hofmann, Christine Howe, Ruth Kershner, Fiona Jackson, Karen Littleton, Neil Mercer, Paul Warwick (UK team); Mariana Alarcón, Nube Estrada, Erika Gil, Kissy Guzmán, Flora Hernández, José Hernández, Haydeé Pedraza, Ana Luisa Rubio, Brenda Itzel Sánchez, Ana Laura Trigo, Maricela Velez (Mexico team). We also thank all of the teachers (especially Lloyd and Tania) and students who participated in our previous research from which examples were taken. We appreciate the support of the Economic and Social Research Council, sponsor of most of the UK team’s work in this area over the years

Aplicación de la topología molecular en la predicción de la inhibición de Trypanosoma cruzi Hexokinasa y un grupo de derivados bifosfonatos

A topological-mathematical model has been arranged to search for new derivatives of bisphosphonate compounds actingas inhibitors against Trypanosoma cruzi hexokinase. By using linear discriminant analysis, a four-variable function wasachieved allowing an accurate prediction of the IC50 for each compound of the training and test series. After carryingout a virtual screening based upon such a model, new structures potentially actives against T. cruzi are proposedSe ha desarrollado un modelo topológico-matemático para la búsqueda de nuevos derivados bisfosfonatos activosfrente a la hexokinasa de Trypanosoma cruzi. Utilizando el análisis lineal discriminante se ha seleccionado una funcióncon cuatro variables capaz de predecir adecuadamente la CI50 para cada compuesto de las series de entrenamientoy test. El modelo propuesto se ha aplicado a una librería molecular y se han propuesto nuevas estructuraspotencialmente activas frente a T. cruzi

La pérdida de fitness de Acinetobacter baumannii resistente a colistina está asociada con una menor capacidad para crecer en condiciones deficientes en hierro.

Motivación: En un estudio anterior demostramos que las cepas de Acinetobacter baumannii que adquieren resistencia a colistina gracias a mutaciones en el sistema PmrAB presentan reducción in vivo del fitness y disminución de la virulencia1. El objetivo del presente estudio es caracterizar el papel del hierro libre en el fitness in vitro de estas cepas. Métodos: Se utilizaron las cepas de A. baumannii ATTCC 19606 (CMI colistina = 0,5 mg/L) y RC64, su derivado colistina-resistente obtenido mediante crecimiento en presencia de colistina (CMI colistina = 64 mg/L)2. Se realizaron curvas de crecimiento durante 24 horas en Mueller Hinton Broth (MHB) y suero humano (SH). Posteriormente, se determinó el crecimiento en Mueller Hinton Agar (MHA) con o sin el quelante de hierro 2,2'-bipiridil (Bip) mediante el cultivo en gotas de concentraciones decrecientes de las cepas (de 8 a 3 Log10 UFC/mL). Además, se determinó la CMI de Bip para ambas cepas, así como la concentración de hierro necesaria para permitir el crecimiento en SH. Por último, se caracterizó el crecimiento de ambas cepas en SH suplementado con Fe2+. Resultados: Ambas cepas presentaron un crecimiento similar al ser cultivadas en MHB; sin embargo, en SH la cepa RC64 mostró un crecimiento reducido. Adicionalmente, RC64 presentó un menor crecimiento en comparación con ATCC 19606 en placas de MHA suplementadas con Bip; sin embargo, cuando se crecieron en MHA sin Bip el crecimiento fue similar. La CMI de Bip en MHB fue de 64 mg/L para la cepa ATCC 19606 y 32 mg/L para RC64. Cuando se suplementó el SH con Fe2+, ATCC 19606 creció sin necesidad de dicho suplemento, mientras que RC64 requirió la adición de 0,5 mg/L de Fe2+. La cepa RC64 presentó una mayor tasa de crecimiento en SH suplementado con Fe2+ en comparación con su crecimiento en SH no suplementado. Conclusiones: La pérdida de fitness y virulencia en Acinetobacter baumannii asociada a la resistencia a colistina adquirida por mutaciones en el sistema PmrAB podría estar relacionada con una menor capacidad para crecer en condiciones pobres en hierro libre

Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

This work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.PostprintPeer reviewe

Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4

The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer

High Diversity of vacA and cagA Helicobacter pylori Genotypes in Patients with and without Gastric Cancer

BACKGROUND: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008), and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003). A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036). A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003). Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. CONCLUSION/SIGNIFICANCE: High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work