Efficient mining of top-k breaker emerging subgraph patterns from graph datasets

This paper introduces a new type of discriminative subgraph pattern called breaker emerging subgraph pattern by introducing three constraints and two new concepts: base and breaker. A breaker emerging sub-graph pattern consists of three subpatterns: a con-strained emerging subgraph pattern, a set of bases and a set of breakers. An efficient approach is pro-posed for the discovery of top-k breaker emerging sub-graph patterns from graph datasets. Experimental re-sults show that the approach is capable of efficiently discovering top-k breaker emerging subgraph patterns from given datasets, is more efficient than two previ-ous methods for mining discriminative subgraph pat-terns. The discovered top-k breaker emerging sub-graph patterns are more informative, more discrim-inative, more accurate and more compact than the minimal distinguishing subgraph patterns. The top-k breaker emerging patterns are more useful for sub-structure analysis, such as molecular fragment analy-sis. © 2009, Australian Computer Society, Inc.

Validation of a multiplex reverse transcription and pre-amplification method using TaqMan(®) MicroRNA assays.

Since the discovery of microRNAs (miRNAs), different approaches have been developed to label, amplify and quantify miRNAs. The TaqMan(®) technology, provided by Applied Biosystems (ABIs), uses a stem-loop reverse transcription primer system to reverse transcribe the RNA and amplify the cDNA. This method is widely used to identify global differences between the expression of 100s of miRNAs across comparative samples. This technique also allows the quantification of the expression of targeted miRNAs to validate observations determined by whole-genome screening or to analyze few specific miRNAs on a large number of samples. Here, we describe the validation of a method published by ABIs on their web site allowing to reverse transcribe and pre-amplify multiple miRNAs and snoRNAs simultaneously. The validation of this protocol was performed on human muscle and plasma samples. Fast and cost efficient, this method achieves an easy and convenient way to screen a relatively large number of miRNAs in parallel.

Mimtags: the use of phage display technology to produce novel protein-specific probes

In recent times the use of protein-specific probes in the field of proteomics has undergone evolutionary changes leading to the discovery of new probing techniques. Protein-specific probes serve two main purposes: epitope mapping and detection assays. One such technique is the use of phage display in the random selection of peptide mimotopes (mimtags) that can tag epitopes of proteins, replacing the use of monoclonal antibodies in detection systems. In this study, phage display technology was used to screen a random peptide library with a biologically active purified human interleukin-4 receptor (IL-4R) and interleukin-13 (IL-13) to identify mimtag candidates that interacted with these proteins. Once identified, the mimtags were commercially synthesised, biotinylated and used for in vitro immunoassays. We have used phage display to identify M13 phage clones that demonstrated specific binding to IL-4R and IL-13 cytokine. A consensus in binding sequences was observed and phage clones characterised had identical peptide sequence motifs. Only one was synthesised for use in further immunoassays, demonstrating significant binding to either IL-4R or IL-13. We have successfully shown the use of phage display to identify and characterise mimtags that specifically bind to their target epitope. Thus, this new method of probing proteins can be used in the future as a novel tool for immunoassay and detection technique, which is cheaper and more rapidly produced and therefore a better alternative to the use of monoclonal antibodies.

Hierarchical dirichlet process for tracking complex topical structure evolution and its application to autism research literature

In this paper we describe a novel framework for the discovery of the topical content of a data corpus, and the tracking of its complex structural changes across the temporal dimension. In contrast to previous work our model does not impose a prior on the rate at which documents are added to the corpus nor does it adopt the Markovian assumption which overly restricts the type of changes that the model can capture. Our key technical contribution is a framework based on (i) discretization of time into epochs, (ii) epoch-wise topic discovery using a hierarchical Dirichlet process-based model, and (iii) a temporal similarity graph which allows for the modelling of complex topic changes: emergence and disappearance, evolution, splitting and merging. The power of the proposed framework is demonstrated on the medical literature corpus concerned with the autism spectrum disorder (ASD) - an increasingly important research subject of significant social and healthcare importance. In addition to the collected ASD literature corpus which we made freely available, our contributions also include two free online tools we built as aids to ASD researchers. These can be used for semantically meaningful navigation and searching, as well as knowledge discovery from this large and rapidly growing corpus of literature.

Stabilizing sparse cox model using statistic and semantic structures in electronic medical records

Stability in clinical prediction models is crucial for transferability between studies, yet has received little attention. The problem is paramount in high dimensional data, which invites sparse models with feature selection capability. We introduce an effective method to stabilize sparse Cox model of time-to-events using statistical and semantic structures inherent in Electronic Medical Records (EMR). Model estimation is stabilized using three feature graphs built from (i) Jaccard similarity among features (ii) aggregation of Jaccard similarity graph and a recently introduced semantic EMR graph (iii) Jaccard similarity among features transferred from a related cohort. Our experiments are conducted on two real world hospital datasets: a heart failure cohort and a diabetes cohort. On two stability measures – the Consistency index and signal-to-noise ratio (SNR) – the use of our proposed methods significantly increased feature stability when compared with the baselines.

BacHbpred: support vector machine methods for the prediction of bacterial hemoglobin-like proteins

The recent upsurge in microbial genome data has revealed that hemoglobin-like (HbL) proteins may be widely distributed among bacteria and that some organisms may carry more than one HbL encoding gene. However, the discovery of HbL proteins has been limited to a small number of bacteria only. This study describes the prediction of HbL proteins and their domain classification using a machine learning approach. Support vector machine (SVM) models were developed for predicting HbL proteins based upon amino acid composition (AC), dipeptide composition (DC), hybrid method (AC + DC), and position specific scoring matrix (PSSM). In addition, we introduce for the first time a new prediction method based on max to min amino acid residue (MM) profiles. The average accuracy, standard deviation (SD), false positive rate (FPR), confusion matrix, and receiver operating characteristic (ROC) were analyzed. We also compared the performance of our proposed models in homology detection databases. The performance of the different approaches was estimated using fivefold cross-validation techniques. Prediction accuracy was further investigated through confusion matrix and ROC curve analysis. All experimental results indicate that the proposed BacHbpred can be a perspective predictor for determination of HbL related proteins. BacHbpred, a web tool, has been developed for HbL prediction.

Learning entry profiles of children with autism from multivariate treatment information using restricted boltzmann machines

Entry profiles can be generated before children with Autism Spectrum Disorders (ASD) begin to traverse an intervention program. They can help evaluate the progress of each child on the dedicated syllabus in addition to enabling narrowing down the best intervention course over time. However, the traits of ASD are expressed in different ways in every individual affected. The resulting spectrum nature of the disorder makes it challenging to discover profiles of children with ASD. Using data from 491 children, traversing the syllabus of a comprehensive intervention program on iPad called TOBY Playpad, we learn the entry profiles of the children based on their age, sex and performance on their first skills of the syllabus. Mixed-variate restricted Boltzmann machines allow us to integrate the heterogeneous data into one model making it a suitable technique. The data based discovery of entry profiles may assist in developing systems that can automatically suggest best suitable paths through the syllabus by clustering the children based on the characteristics they present at the beginning of the program. This may open the pathway for personalised intervention.

The politics of memory in Harold Pinter's Ashes to Ashes

The present work proposes an investigation of the treatment given to memory in Pinter’s latest play, Ashes to Ashes, and of its function in the development of Pinter’s work. In order to do that, different aspects of the construction of meaning in the theatre are analysed, so that the specificity of its reception is determined. A survey of techniques used to present information, time and space in the theatre is made. The analytical drama, the history drama, and the theatre of the absurd are defined. After that, the evolution of the author’s work is analysed to determine what characterises Pinter’s work, while at the same time determining how his treatment of themes like menace, memory, and political oppression of the individual has evolved. Finally, a detailed survey of the apparently disconnected elements that are mentioned in Ashes to Ashes is made. The intertextual analysis allied to a study of the analytical form as used in this play enables the discovery of several layers of meaning. Through the connection established between the Holocaust and man’s fall followed by expulsion from Eden, Pinter examines the use of memory as a way of dealing with personal and collective responsibility and guilt. It is through the recovery of memory (also through writing) that the present can establish a critical and responsible relation with the past.

Cozinha da Madeira website: the online touchpoint for a sustainability oriented service of Madeira Island

Over the past several years technology has been evolving in a way that it has become crucial for most businesses and companies to have interactive technology enabled touchpoints available online. Such interactive touchpoints can be developed as mobile application, webpages, or even through social networks. In the end such touchpoints will most surely represent the most easily reachable and marketable side of the business. Today selling a product alone is no longer enough to make consumers satisfied and complete, businesses and business models are changing. Increasingly, companies are choosing to not just sell products but to combine both sale and service. These service-based approaches will provide the client with a unique and personalized experience of what the company is selling. By selling a service the company transmits values that are more complex than the simple selling of a product. A service is something immaterial, happens over time and exists in the moment of the delivery. When conceiving and designing services, the use of the new technologies becomes a crucial step in order to craft touchpoints that facilitate the whole experience cycle of the service, from attracting, orienting, interacting and retaining the client, as well as providing later support to the consumer to advocate for the service itself. This thesis reports on the design and implementation of the online touchpoint of Cozinha da Madeira, which is a service designed to support tourism, specifically promoting the discovery of tradition and landscapes in the island of Madeira. Such touchpoint developed in the form of a website, embodies completely or partially various stages of the Service Experience cycle, from attracting and connecting, orienting, interacting as well as retaining and advocating. Through this thesis we will describe the design and implementation of such touchpoint as well as the evaluation and possible future implications.

Efeito anti-inflamatório do heparinóide isolado do camarão Litopenaeus vannamei sobre a peritonite aguda

In recent years the heparin has been the subject of several studies that aim to expand its use as a therapeutic agent, due to its ability to modulate the activity of various proteins that play important roles in the regulation of pathophysiological processes. In several experiments and preclinical trials, heparin has demonstrated an anti-inflammatory role. However, its clinical use is limited, due to its strong anticoagulant activity and hemorrhagic complications. For this reason, considerable efforts have been employed in discovery of heparin analogous (heparinoid) with reduced side effects, that retain the anti-inflammatory properties of heparin. In this context, a heparinoid obtained from the head of Litopenaeus vannamei shrimp, which presents a structural similarity to heparin, showed, in previous studies, anti-inflammatory activity in a model of acute peritonitis with reduced anticoagulant effect in vitro and low hemorrhagic activity. Thus, the present work had as objective to evaluate the effect the heparinoid of the cephalothorax of gray shrimp on the acute inflammatory response in different times (3 or 6 hours after the induction of inflammatory stimulus), using the model of acute peritonitis induced in mice. It was also analyzed the HL effect over the activity of elastase, an enzyme involved in leukocyte recruitment. Furthermore to check if the different doses of heparin and heparinoid change the hemostatic balance in vivo, was assessed the effect of these compounds on the plasma clotting time in animals submitted to inflammation. The results show that in 3 hours, all doses of heparinoid were able to prevent efficiently in the acute inflammatory process without any anticoagulant effects, unlike the extrapolation dose of heparin, which has induced a large hemorrhage due its high anticoagulant activity. However, 6 hours after induction of inflammation, only the dosages of 0.1 and 1.0 μg/Kg of heparin and 1.0 μg/Kg of heparinoid kept anti-migratory effect, without changing of the hemostatic balance. These results indicate that the anti-migratory effect of theses compounds depends on the dosage and time of inflammatory stimulus. The HL and heparin were also able to inhibit the activity of the enzyme elastase. The discovery of this bioactive compound in the cephalothorax of shrimps can arouse great interest in biotechnology, since this compound could be useful as a structural model interesting for the development of new therapeutic agents for peritonitis

Characterization of bovine transcripts preferentially expressed in testis and with a putative role in spermatogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Assessment of estrogenic, mutagenic and antimutagenic activity of nemorosone

Currently, a wide range of research involving natural products is focused on the discovery of new drugs in many different therapeutic areas. A great number of the synthetic compounds on the market were derived from natural products, especially plants. Nemorosone is the major constituent of the floral resin of Clusia rosea Jacq., Clusiaceae, and in Cuban propolis. In vitro studies have shown cytotoxic activity in this substance against various tumor cell lines, including those resistant to various cytotoxic drugs, whereas it has low cytotoxicity to non-tumoral cells. Therefore, in order to characterize the biological activity of nemorosone, a substance with potential antitumor activity, and in view of preclinical testing of the toxicity of drug candidate compounds, the main aim of this study was to determine the mutagenic and antimutagenic activity of nemorosone by the Ames test, using the strains TA97a, TA98, TA100 and TA102 of Salmonella typhimurium. Secondly, to characterize the estrogenic activity in an experimental recombinant yeast model (Recombinant Yeast Assay) mutagenic activity was observed at in any of the concentrations in any of the test strains. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine (NPD), mitomycin C (MMC) and aflatoxin B1 (AFL). Nemorosone showed moderate antimutagenic activity (inhibition level 31%), in strain TA100 in the presence of AFL, and strong antimutagenic activity in TA102 against MMC (inhibition level 53%). Estrogenic activity was observed, with an EEq of 0.41±0.16 nM at various tested concentrations.

Morphology of the eggs of the genus Belminus (Hemiptera: Reduviidae: Triatominae) by optical and scanning electron microscopy

The external morphology of eggs of the species Belminus corredori Galvao & Angulo, 2006, Belminus herreri Lent & Wygodzinsky, 1979 and Belminus ferroae Sandoval, Pabon, Jurberg & Galvao, 2007 is described for the first time using scanning electron microscopy (SEM). Females lay one egg at a time; the shape of the egg is oval with lateral flattening, a rounded caudal area and a true and simple convex operculum. The average size of the egg among these species is 0.51-0.58 mm in length and 0.36-0.4 mm in width. As a generic character we highlight the discovery of a chorion rim with one to four grooves always joined to the micropyles. All species present a clear polygonal pattern only in the operculum and in the egg's cephalic region, while the median and caudal regions show a smooth appearance, features that are shared only with the eggs of the genus Alberprosenia. A discriminant analysis of the polygonal design of the operculum proved to be useful for the identification of the species.

Mutagenicity and antimutagenicity of (-)-hinokinin a trypanosomicidal compound measured by Salmonella microsome and comet assays

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The effect of pH on horseradish peroxidase-catalyzed oxidation of melatonin: production of N-1-acetyl-N-2-formyl-5-methoxykynuramine versus radical-mediated degradation

There is a g-rowing body of evidence that melatonin and its oxidation product, N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK), have anti-inflammatory properties. From a nutritional point of view, the discovery of melatonin in plant tissues emphasizes the importance of its relationship with plant peroxidases. Here we found that the pH of the reaction mixture has a profound influence in the reaction rate and products distribution when melatonin is oxidized by the plant enzyme horseradish peroxidase. At pH 5.5. 1 mm of melatonin was almost completely oxidized within 2 min, whereas only about 3% was consumed at pH 7.4. However, the relative yield of AFMK was higher in physiological pH. Radical-mediated oxidation products, including 2-hydroxymelatonin a dimer of, 2-hydroxymelatonin and O-demethylated dimer of melatonin account for the fast consumption of melatonin at pH 5.5. The higher production of AFMK at pH 7.4 was explained by the involvement of compound III of peroxidases as evidenced by spectral studies. on the other hand, the fast oxidative degradation at pH 5.5 was explained by the classic peroxidase cycle.