Exploring chemical conversions in metabolic networks by tracing atoms transitions

Dissertação de mestrado em Bioinformática

Engineering modular viral scaffolds for targeted bacterial population editing

Bacteria are central to human health and disease, but existing tools to edit microbial consortia are limited. For example, broad-spectrum antibiotics are unable to precisely manipulate bacterial communities. Bacteriophages can provide highly specific targeting of bacteria, but assembling well-defined phage cocktails solely with natural phages can be a time-, labor- and cost-intensive process. Here, we present a synthetic biology strategy to modulate phage host ranges by engineering phage genomes in Saccharomyces cerevisiae. We used this technology to redirect Escherichia coli phage scaffolds to target pathogenic Yersinia and Klebsiella bacteria, and conversely, Klebsiella phage scaffolds to target E. coli by modular swapping of phage tail components. The synthetic phages achieved efficient killing of their new target bacteria and were used to selectively remove bacteria from multi-species bacterial communities with cocktails based on common viral scaffolds. We envision this approach accelerating phage biology studies and enabling new technologies for bacterial population editing.

Reconstructing transcriptional regulatory networks using data integration and text mining

Transcriptional Regulatory Networks (TRNs) are powerful tool for representing several interactions that occur within a cell. Recent studies have provided information to help researchers in the tasks of building and understanding these networks. One of the major sources of information to build TRNs is biomedical literature. However, due to the rapidly increasing number of scientific papers, it is quite difficult to analyse the large amount of papers that have been published about this subject. This fact has heightened the importance of Biomedical Text Mining approaches in this task. Also, owing to the lack of adequate standards, as the number of databases increases, several inconsistencies concerning gene and protein names and identifiers are common. In this work, we developed an integrated approach for the reconstruction of TRNs that retrieve the relevant information from important biological databases and insert it into a unique repository, named KREN. Also, we applied text mining techniques over this integrated repository to build TRNs. However, was necessary to create a dictionary of names and synonyms associated with these entities and also develop an approach that retrieves all the abstracts from the related scientific papers stored on PubMed, in order to create a corpora of data about genes. Furthermore, these tasks were integrated into @Note, a software system that allows to use some methods from the Biomedical Text Mining field, including an algorithms for Named Entity Recognition (NER), extraction of all relevant terms from publication abstracts, extraction relationships between biological entities (genes, proteins and transcription factors). And finally, extended this tool to allow the reconstruction Transcriptional Regulatory Networks through using scientific literature.

Artificial neural networks in diagnosis of liver diseases

Liver diseases have severe patients’ consequences, being one of the main causes of premature death. These facts reveal the centrality of one`s daily habits, and how important it is the early diagnosis of these kind of illnesses, not only to the patients themselves, but also to the society in general. Therefore, this work will focus on the development of a diagnosis support system to these kind of maladies, built under a formal framework based on Logic Programming, in terms of its knowledge representation and reasoning procedures, complemented with an approach to computing grounded on Artificial Neural Networks.

Logic programming and artificial neural networks in breast cancer detection

About 90% of breast cancers do not cause or are capable of producing death if detected at an early stage and treated properly. Indeed, it is still not known a specific cause for the illness. It may be not only a beginning, but also a set of associations that will determine the onset of the disease. Undeniably, there are some factors that seem to be associated with the boosted risk of the malady. Pondering the present study, different breast cancer risk assessment models where considered. It is our intention to develop a hybrid decision support system under a formal framework based on Logic Programming for knowledge representation and reasoning, complemented with an approach to computing centered on Artificial Neural Networks, to evaluate the risk of developing breast cancer and the respective Degree-of-Confidence that one has on such a happening.

User expectations for media sharing practices in open display networks

Open Display Networks have the potential to allow many content creators to publish their media to an open-ended set of screen displays. However, this raises the issue of how to match that content to the right displays. In this study, we aim to understand how the perceived utility of particular media sharing scenarios is affected by three independent variables, more specifically: (a) the locativeness of the content being shared; (b) how personal that content is and (c) the scope in which it is being shared. To assess these effects, we composed a set of 24 media sharing scenarios embedded with different treatments of our three independent variables. We then asked 100 participants to express their perception of the relevance of those scenarios. The results suggest a clear preference for scenarios where content is both local and directly related to the person that is publishing it. This is in stark contrast to the types of content that are commonly found in public displays, and confirms the opportunity that open displays networks may represent a new media for self-expression. This novel understanding may inform the design of new publication paradigms that will enable people to share media across the display networks.

A hybrid MAC Scheme to improve the transmission performance in body sensor networks

Wireless body sensor networks (WBSNs) constitute a key technology for closing the loop between patients and healthcare providers, as WBSNs provide sensing ability, as well as mobility and portability, essential characteristics for wide acceptance of wireless healthcare technology. However, one important and difficult aspect of WBSNs is to provide data transmissions with quality of service, among other factors due to the antennas being small size and placed close to the body. Such transmissions cannot be fully provided without the assumption of a MAC protocol that solves the problems of the medium sharing. A vast number of MAC protocols conceived for wireless networks are based on random or scheduled schemes. This paper studies firstly the suitability of two MAC protocols, one using CSMA and the other TDMA, to transmit directly to the base station the signals collected continuously from multiple sensor nodes placed on the human body. Tests in a real scenario show that the beaconed TDMA MAC protocol presents an average packet loss ratio lower than CSMA. However, the average packet loss ratio is above 1.0 %. To improve this performance, which is of vital importance in areas such as e-health and ambient assisted living, a hybrid TDMA/CSMA scheme is proposed and tested in a real scenario with two WBSNs and four sensor nodes per WBSN. An average packet loss ratio lower than 0.2 % was obtained with the hybrid scheme. To achieve this significant improvement, the hybrid scheme uses a lightweight algorithm to control dynamically the start of the superframes. Scalability and traffic rate variation tests show that this strategy allows approximately ten WBSNs operating simultaneously without significant performance degradation.

Concurrency detection on finish-to-start activity precedence networks

We explore the finish-to-start precedence relations of project activities used in scheduling problems. From these relations, we devise a method to identify groups of activities that could execute concurrently, i.e. activities in the same group can all execute in parallel. The method derives a new set of relations to describe the concurrency. Then, it is represented by an undirected graph and the maximal cliques problem identifies the groups. We provide a running example with a project from our previous studies in resource constrained project cost minimization together with an example application on the concurrency detection method: the evaluation of the resource stress.

Nonlinear behavior of gelatin networks reveals a hierarchical structure

We investigate the strain hardening behavior of various gelatin networks-namely physical gelatin gel, chemically cross-linked gelatin gel, and a hybrid gel made of a combination of the former two-under large shear deformations using the pre-stress, strain ramp, and large amplitude oscillations shear protocols. Further, the internal structures of physical gelatin gels and chemically cross-linked gelatin gels were characterized by small angle neutron scattering (SANS) to enable their internal structures to be correlated with their nonlinear rheology. The Kratky plots of SANS data demonstrate the presence of small cross-linked aggregates within the chemically cross-linked network whereas, in the physical gelatin gels, a relatively homogeneous structure is observed. Through model fitting to the scattering data, we were able to obtain structural parameters, such as the correlation length (ξ), the cross-sectional polymer chain radius (Rc) and the fractal dimension (df) of the gel networks. The fractal dimension df obtained from the SANS data of the physical and chemically cross-linked gels is 1.31 and 1.53, respectively. These values are in excellent agreement with the ones obtained from a generalized nonlinear elastic theory that has been used to fit the stress-strain curves. The chemical cross-linking that generates coils and aggregates hinders the free stretching of the triple helix bundles in the physical gels.

Quantifying, generating and mitigating radio interference in Low-Power Wireless Networks

Doctoral Programme in Telecommunication - MAP-tele

High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16

Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention.

Flow updating: fault-tolerant aggregation for dynamic networks

Documento submetido para revisão pelos pares. A publicar em Journal of Parallel and Distributed Computing. ISSN 0743-7315

Hierarchical modelling of timber reference properties using probabilistic methods: Maximum Likelihood Method, Bayesian Methods and Probability Networks

In recent decades, an increased interest has been evidenced in the research on multi-scale hierarchical modelling in the field of mechanics, and also in the field of wood products and timber engineering. One of the main motivations for hierar-chical modelling is to understand how properties, composition and structure at lower scale levels may influence and be used to predict the material properties on a macroscopic and structural engineering scale. This chapter presents the applicability of statistic and probabilistic methods, such as the Maximum Likelihood method and Bayesian methods, in the representation of timber’s mechanical properties and its inference accounting to prior information obtained in different importance scales. These methods allow to analyse distinct timber’s reference properties, such as density, bending stiffness and strength, and hierarchically consider information obtained through different non, semi or destructive tests. The basis and fundaments of the methods are described and also recommendations and limitations are discussed. The methods may be used in several contexts, however require an expert’s knowledge to assess the correct statistic fitting and define the correlation arrangement between properties.

From perfect strangers to research partners: a study of relationships, resource sharing and perceived benefits within R&D cooperation networks

Doctoral thesis in Marketing and Strategy.