Gene Sets Net Correlations Analysis (GSNCA): a multivariate differential coexpression test for gene sets

Motivation: To date, Gene Set Analysis (GSA) approaches primarily focus on identifying differentially expressed gene sets (pathways). Methods for identifying differentially coexpressed pathways also exist but are mostly based on aggregated pairwise correlations, or other pairwise measures of coexpression. Instead, we propose Gene Sets Net Correlations Analysis (GSNCA), a multivariate differential coexpression test that accounts for the complete correlation structure between genes.

Results: In GSNCA, weight factors are assigned to genes in proportion to the genes' cross-correlations (intergene correlations). The problem of finding the weight vectors is formulated as an eigenvector problem with a unique solution. GSNCA tests the null hypothesis that for a gene set there is no difference in the weight vectors of the genes between two conditions. In simulation studies and the analyses of experimental data, we demonstrate that GSNCA, indeed, captures changes in the structure of genes' cross-correlations rather than differences in the averaged pairwise correlations. Thus, GSNCA infers differences in coexpression networks, however, bypassing method-dependent steps of network inference. As an additional result from GSNCA, we define hub genes as genes with the largest weights and show that these genes correspond frequently to major and specific pathway regulators, as well as to genes that are most affected by the biological difference between two conditions. In summary, GSNCA is a new approach for the analysis of differentially coexpressed pathways that also evaluates the importance of the genes in the pathways, thus providing unique information that may result in the generation of novel biological hypotheses.

Research agendas for the sustainable management of tropical peatland in Malaysia

There is a need for coordinated research for the sustainable management of tropical peatland. Malaysia has 6% of global tropical peat by area and peatlands there are subject to land use change at an unprecedented rate. This paper describes a stakeholder engagement exercise that identified 95 priority research questions for peatland in Malaysia, organized into nine themes. Analysis revealed the need for fundamental scientific research, with strong representation across the themes of environmental change, ecosystem services, and conversion, disturbance and degradation. Considerable uncertainty remains about Malaysia's baseline conditions for peatland, including questions over total remaining area of peatland, water table depths, soil characteristics, hydrological function, biogeochemical processes and ecology. More applied and multidisciplinary studies involving researchers from the social sciences are required. The future sustainability of Malaysian peatland relies on coordinating research agendas via a ‘knowledge hub’ of researchers, strengthening the role of peatlands in land-use planning and development processes, stricter policy enforcement, and bridging the divide between national and provincial governance. Integration of the economic value of peatlands into existing planning regimes is also a stakeholder priority. Finally, current research needs to be better communicated for the benefit of the research community, for improved societal understanding and to inform policy processes.

Revolting Arts or Spatial Democracy: Performances of popular arts during the Egyptian Revolution?

This paper investigates how spatial practices of Public art performance had transformed public space from being a congested traffic hub into an active and animated space for resistance that was equally accessible to different factions, social strata, media outlets and urban society, determined by popular culture and social responsibility. Tahrir Square was reproduced, in a process of “space adaptation” using Henri Lefebvre’s term, to accommodate forms of social organization and administration.205 Among the spatial patterns of activities detected and analyzed this paper focus on particular forms of mass practices of art and freedom of expression that succeeded to transform Tahrir square into performative space and commemorate its spatial events. It attempts to interrogate how the power of artistic interventions has recalled socio-cultural memory through spatial forms that have negotiated middle grounds between deeply segregated political and social groups in moments of utopian democracy. Through analytical surveys and decoding of media recordings of the events, direct interviews with involved actors and witnesses, this paper offers insight into the ways protesters lent their artistry capacity to the performance of resistance to become an act of spatial festivity or commemoration of events. The paper presents series of analytical maps tracing how the role of art has shifted significantly from traditional freedom of expression modes as narrative of resistance into more sophisticated spatial performative ones that take on a new spatial vibrancy and purpose.

Improving Feasibility of Point to Point Operations Through Civil Aerial Refuelling

Re-imagining of the aerial transportation system has become increasingly important as the need for significant environmental and economic efficiency gains has become ever more prevalent. A number of studies have highlighted the benefits of the adoption of air to air refuelling within civil aviation. However, it also opens up the potential for increased flexibility in operations through smaller aircraft, shifting emphasis away from the traditional hub and spoke method of operation towards the more flexible Point to Point operations. It is proposed here that one technology can act as an enabler for the other, realising benefits that neither can realise as a standalone. The impact of an air-toair refuelling enabled point to point system is discussed, and the affect on economic and environmental cost metrics relative to traditional operations evaluated. An idealised airport configuration study shows the difference in fuel burn for point to point networks to vary from -23% to 28% from that of Hub and Spoke depending on the configuration. The sensitive natures of the concepts are further explored in a second study based on real airport configurations. The complex effect of the choice of a Point to Point or Hub and Spoke system on fuel burn, operating cost and revenue potential is highlighted. Fuel burn savings of 15% can be experienced with AAR over traditional refuelling operations, with point to point networks increasing the available seat miles (by approximately 20%) without a proportional increase in operating cost or fuel.

A Numerical Study of Inlet Geometry for a Low Inertia Mixed Flow Turbocharger Turbine

Mixed flow turbines can offer improvements over typical radial turbines used in automotive turbochargers, with regards to transient performance and low velocity ratio efficiency. Turbine rotor mass dominates the rotating inertia of the turbocharger, and any reductions of mass in the outer radii of the wheel, including the rotor back-disk, can significantly reduce this inertia and improve the acceleration of the assembly. Off-design, low velocity ratio conditions are typified by highly tangential flow at the rotor inlet and a non-zero inlet blade angle is preferred for such operating conditions. This is achievable in a Mixed Flow Turbine without increasing bending stresses within the rotor blade, which is beneficial in high speed and high inlet temperature turbine design. A range of mixed flow turbine rotors was designed with varying cone angle and inlet blade angle and each was assessed at a number of operating points. These rotors were based on an existing radial flow turbine, and both the hub and shroud contours and exducer geometry were maintained. The inertia of each rotor was also considered. The results indicated that there was a trade-off between efficiency and inertia for the rotors and certain designs may be beneficial for the transient performance of downsized, turbocharged engines.

SWAT-1: The effectiveness of a 'site visit' intervention on recruitment rates in a multi-centre randomised trial

Background: Recruitment rates in multi-centre randomised trials often fall below target recruitment rates, causing problems for study outcomes. The Studies Within A Trial (SWAT) Programme, established by the All-Ireland Hub for Trials Methodology Research in collaboration with the Medical Research Council Network of Hubs in the United Kingdom and others, is developing methods for evaluating aspects of trial methodology through the conduct of research within research. A recently published design for a SWAT-1 provides a protocol for evaluating the effect of a site visit by the principal investigator on recruitment in multi-centre trials.

Methods: Using the SWAT-1 design, the effect of a site visit, with the sole purpose of discussing trial recruitment, on recruitment rates in a large multicentre trial in the Republic of Ireland was evaluated. A controlled before and after intervention comparison was used, where the date of the site visit provides the time point for the intervention, and for the comparison to control sites. Site A received the intervention. Site B and Site C acted as the controls. Z-scores for proportions were calculated to determine within site recruitment differences. Odds ratios and 95% confidence intervals were calculated to determine between site recruitment differences.

Results: Recruitment rates were increased in Site A post-intervention (17% and 14% percentage point increases at 1 and 3 months, respectively). No differences in recruitment occurred in Site B or in Site C. Comparing between site differences, at 3 months post-intervention, a statistically significant difference was detected in favour of higher recruitment in Site A (34% versus 25%; odds ratio 1.57, 95% confidence interval 1.09 to 2.26).

Conclusions: This is the first reported example of a study in the SWAT programme.. It provides evidence that a site visit, combined with a scheduled meeting, increases recruitment in a clinical trial. Using this example, other researchers might be encouraged to consider conducting a similar study, allowing the findings of future SWAT-1s to be compared and combined, so that higher level evidence on the effect of a site visit by the principal investigator can be obtained.

Urothelial cancer gene regulatory networks inferred from large-scale RNAseq, Bead and Oligo gene expression data

BACKGROUND: Urothelial pathogenesis is a complex process driven by an underlying network of interconnected genes. The identification of novel genomic target regions and gene targets that drive urothelial carcinogenesis is crucial in order to improve our current limited understanding of urothelial cancer (UC) on the molecular level. The inference of genome-wide gene regulatory networks (GRN) from large-scale gene expression data provides a promising approach for a detailed investigation of the underlying network structure associated to urothelial carcinogenesis.

METHODS: In our study we inferred and compared three GRNs by the application of the BC3Net inference algorithm to large-scale transitional cell carcinoma gene expression data sets from Illumina RNAseq (179 samples), Illumina Bead arrays (165 samples) and Affymetrix Oligo microarrays (188 samples). We investigated the structural and functional properties of GRNs for the identification of molecular targets associated to urothelial cancer.

RESULTS: We found that the urothelial cancer (UC) GRNs show a significant enrichment of subnetworks that are associated with known cancer hallmarks including cell cycle, immune response, signaling, differentiation and translation. Interestingly, the most prominent subnetworks of co-located genes were found on chromosome regions 5q31.3 (RNAseq), 8q24.3 (Oligo) and 1q23.3 (Bead), which all represent known genomic regions frequently deregulated or aberated in urothelial cancer and other cancer types. Furthermore, the identified hub genes of the individual GRNs, e.g., HID1/DMC1 (tumor development), RNF17/TDRD4 (cancer antigen) and CYP4A11 (angiogenesis/ metastasis) are known cancer associated markers. The GRNs were highly dataset specific on the interaction level between individual genes, but showed large similarities on the biological function level represented by subnetworks. Remarkably, the RNAseq UC GRN showed twice the proportion of significant functional subnetworks. Based on our analysis of inferential and experimental networks the Bead UC GRN showed the lowest performance compared to the RNAseq and Oligo UC GRNs.

CONCLUSION: To our knowledge, this is the first study investigating genome-scale UC GRNs. RNAseq based gene expression data is the data platform of choice for a GRN inference. Our study offers new avenues for the identification of novel putative diagnostic targets for subsequent studies in bladder tumors.

Hierarchical energy management system for multi-source multi-product microgrids

This paper proposes a hierarchical energy management system for multi-source multi-product (MSMP) microgrids. Traditional energy hub based scheduling method is combined with a hierarchical control structure to incorporate transient characteristics of natural gas flow and dynamics of energy converters in microgrids. The hierarchical EMS includes a supervisory control layer, an optimizing control layer, and an execution control layer. In order to efficiently accommodate the systems multi time-scale characteristics, the optimizing control layer is decomposed into three sub-layers: slow, medium and fast. Thermal, gas and electrical management systems are integrated into the slow, medium, and fast control layer, respectively. Compared with wind energy, solar energy is easier to integrate and more suitable for the microgrid environment, therefore, potential impacts of the hierarchical EMS on MSMP microgrids is investigated based on a building energy system integrating photovoltaic and microturbines. Numerical studies indicate that by using a hierarchical EMS, MSMP microgrids can be economically operated. Also, interactions among thermal, gas, and electrical system can be effectively managed.

Study on Hybrid Heat-Gas-Power Flow Algorithm for Integrated Community Energy System: 区域综合能源系统电/气/热混合潮流算法研究

With the integration of combined heat and power (CHP) units, air-conditioners and gas boilers, power, gas, and heat systems are becoming tightly linked to each other in the integrated community energy system (ICES). Interactions among the three systems are not well captured by traditional methods. To address this issue, a hybrid power-gas-heat flow calculation method was developed in this paper. In the proposed method, an energy hub model was presented to describe interactions among the three systems incorporating various CHP operating modes. In addition, three operating modes were proposed for the ICES including fully decoupled, partially coupled, and fully coupled. Numerical results indicated that the proposed algorithm can be used in the steady-state analysis of the ICES and reflect interactions among various energy systems.

Representing Irishness in Belfast’s Gaeltacht Quarter

This paper examines a place-making project in post-conflict Belfast, analyzing efforts to transform an area which has often been used as a byword for militant Irish nationalism and social deprivation into an inclusive, vibrant tourist destination and cultural hub themed around the Irish language (called the "Gaeltacht Quarter‟). The antagonistic and territorial assumptions about place that characterize divided cities now co-exist with global trends towards the commodification of difference as recreation or spectacle, and longstanding struggles over the representation of contested identities are intertwined with the struggle to compete for international tourism and investment. The proliferation of officially themed quarters in many cities across the world reflects the enthusiasm with which planning authorities have embraced the vision of difference as a benign resource for the creation of tourist revenue. Yet, analysis of „quartering‟ processes reveals that such commodification does not neutralise or evade the political potency of naming, representing and delimiting cultural difference. Indeed, this paper argues that such projects offer a valuable insight into the inseparable roles of physical and representational space as both loci and catalysts of contestation in urban conflicts. Bringing together a wide range of public and private interest groups, projects redefining parts of Belfast as distinctive quarters have been explicitly linked with efforts to deterritorialize the city. The creation of bounded, themed spaces as an attempt to leave behind the ethno-sectarian geographical segregation that parts of Belfast still experience has its particular ironies, but is in many ways typical of contemporary trends in urban planning. The Gaeltacht Quarter exemplifies both the importance and the challenge of representation within cities where culturally distinguishing features have acted as markers of violent division, and where negotiations about how to successfully encompass difference necessarily address multiple local and international audiences simultaneously.

A Numerical Study of the Flow Fields in a Highly Off-Design Variable Geometry Turbine

Conventionally, radial turbines have almost exclusively used radially fibred blades. While issues of mechanical integrity are paramount, there may be opportunities for improving turbine efficiency through a 3D blade design without exceeding mechanical limits. Off-design performance and understanding of the secondary flow structures now plays a vital role in the design decisions made for automotive turbocharger turbines. Of particular interest is extracting more energy at high pressure ratios and lower rotational speeds. Operating in this region means the rotor will experience high values of positive incidence at the inlet. A CFD analysis has been carried out on a scaled automotive turbine utilizing a swing vane stator system. To date no open literature exists on the flow structures present in a standard VGT system. Investigations were carried out on a 90 mm diameter rotor with the stator vane at the maximum, minimum and 25% mass flow rate positions. In addition stator vane endwall clearance existed at the hub side. From investigation of the internal flow fields of the baseline rotor, a number of areas that could be optimized in the future with three dimensional blading were identified. The blade loading and tip leakage flow near inlet play a significant role in the flow development further downstream at all stator vane positions. It was found that tip leakage flow and flow separation at off-design conditions could be reduced by employing back swept blading and redistributing the blade loading. This could potentially reduce the extent of the secondary flow structures found in the present study.

Integrative analysis of chemo-transcriptomic profiles for drug-feature specific gene expression signatures

One of the major challenges in systems biology is to understand the complex responses of a biological system to external perturbations or internal signalling depending on its biological conditions. Genome-wide transcriptomic profiling of cellular systems under various chemical perturbations allows the manifestation of certain features of the chemicals through their transcriptomic expression profiles. The insights obtained may help to establish the connections between human diseases, associated genes and therapeutic drugs. The main objective of this study was to systematically analyse cellular gene expression data under various drug treatments to elucidate drug-feature specific transcriptomic signatures. We first extracted drug-related information (drug features) from the collected textual description of DrugBank entries using text-mining techniques. A novel statistical method employing orthogonal least square learning was proposed to obtain drug-feature-specific signatures by integrating gene expression with DrugBank data. To obtain robust signatures from noisy input datasets, a stringent ensemble approach was applied with the combination of three techniques: resampling, leave-one-out cross validation, and aggregation. The validation experiments showed that the proposed method has the capacity of extracting biologically meaningful drug-feature-specific gene expression signatures. It was also shown that most of signature genes are connected with common hub genes by regulatory network analysis. The common hub genes were further shown to be related to general drug metabolism by Gene Ontology analysis. Each set of genes has relatively few interactions with other sets, indicating the modular nature of each signature and its drug-feature-specificity. Based on Gene Ontology analysis, we also found that each set of drug feature (DF)-specific genes were indeed enriched in biological processes related to the drug feature. The results of these experiments demonstrated the pot- ntial of the method for predicting certain features of new drugs using their transcriptomic profiles, providing a useful methodological framework and a valuable resource for drug development and characterization.

A telematic platform towards regional connected healthcare

As tecnologias de informação e comunicação na área da saúde não são só um instrumento para a boa gestão de informação, mas antes um fator estratégico para uma prestação de cuidados mais eficiente e segura. As tecnologias de informação são um pilar para que os sistemas de saúde evoluam em direção a um modelo centrado no cidadão, no qual um conjunto abrangente de informação do doente deve estar automaticamente disponível para as equipas que lhe prestam cuidados, independentemente de onde foi gerada (local geográfico ou sistema). Este tipo de utilização segura e agregada da informação clínica é posta em causa pela fragmentação generalizada das implementações de sistemas de informação em saúde. Várias aproximações têm sido propostas para colmatar as limitações decorrentes das chamadas “ilhas de informação” na saúde, desde a centralização total (um sistema único), à utilização de redes descentralizadas de troca de mensagens clínicas. Neste trabalho, propomos a utilização de uma camada de unificação baseada em serviços, através da federação de fontes de informação heterogéneas. Este agregador de informação clínica fornece a base necessária para desenvolver aplicações com uma lógica regional, que demostrámos com a implementação de um sistema de registo de saúde eletrónico virtual. Ao contrário dos métodos baseados em mensagens clínicas ponto-a-ponto, populares na integração de sistemas em saúde, desenvolvemos um middleware segundo os padrões de arquitetura J2EE, no qual a informação federada é expressa como um modelo de objetos, acessível através de interfaces de programação. A arquitetura proposta foi instanciada na Rede Telemática de Saúde, uma plataforma instalada na região de Aveiro que liga oito instituições parceiras (dois hospitais e seis centros de saúde), cobrindo ~350.000 cidadãos, utilizada por ~350 profissionais registados e que permite acesso a mais de 19.000.000 de episódios. Para além da plataforma colaborativa regional para a saúde (RTSys), introduzimos uma segunda linha de investigação, procurando fazer a ponte entre as redes para a prestação de cuidados e as redes para a computação científica. Neste segundo cenário, propomos a utilização dos modelos de computação Grid para viabilizar a utilização e integração massiva de informação biomédica. A arquitetura proposta (não implementada) permite o acesso a infraestruturas de e-Ciência existentes para criar repositórios de informação clínica para aplicações em saúde.

O quadro interativo na aula de inglês : desenvolvimento de práticas comunicativas

Na sociedade da informação, o papel da escola como centro transmissor de conhecimentos está a perder relevância face ao crescente número de fontes de informação alternativas, ricas em conteúdos e de fácil acesso. A alteração de paradigmas cria a necessidade de se introduzirem nos contextos educacionais novas ferramentas e que se adequem estratégias que permitam motivar e ensinar os aprendentes a procurarem e a selecionarem essa informação, participando, desta forma, ativamente na construção do conhecimento. Neste contexto, consideramos que o quadro interativo, pela sua capacidade de funcionar como hub digital, permite integrar recursos dinâmicos e interativos facilitadores do acesso ao conhecimento e à informação. A dissertação que apresentamos, “O Quadro Interativo na aula de inglês: desenvolvimento de práticas comunicativas”, situa-se na área do Multimédia em Educação e, mais especificamente, no domínio da tecnologia e pedagogia em sala de aula. A investigação foi desenhada em torno de um projeto de implementação de quadros interativos (Inov@r com QI) em agrupamentos/escolas do interior do país, associado a um Centro de Formação. A partir de uma investigação qualitativa mista, baseada no tracer study (análise documental, entrevistas e questionários) e no estudo etnográfico (aulas observadas, entrevistas e questionários), procurámos evidenciar a forma como essa tecnologia levou à integração de recursos e à adoção de estratégias promotoras de um ensino e aprendizagem ativo, centrado no aprendente e criando dinâmicas de interação e comunicação facilitadoras do desenvolvimento da competência comunicativa. Os resultados obtidos revelam que a introdução do quadro interativo produz efeitos positivos no ensino e aprendizagem do inglês. A sua integração em contexto de sala de aula abre espaço a um conjunto de potencialidades pedagógicas, promove o uso de recursos digitais variados; leva a uma diversificação de abordagens metodológicas que promovem a interação, criando espaços que levam ao desenvolvimento da competência comunicativa. No entanto, para tornar a introdução do quadro interativo mais eficaz, como ferramenta educativa no processo de ensino e aprendizagem, devemos ter em conta que esse processo de introdução do quadro deve ser planeada e refletida, devendo ter em conta uma nova realidade de conceitos, a tecnologia e as literacias necessárias para uma implementação eficaz. Os docentes devem ser acompanhados, ter acesso a formação técnica e pedagógica; e a possibilidade de integrarem um espaço de colaboração e partilha, como forma mais eficaz de se libertarem de práticas centradas no docente e orientadas apenas para a aquisição de conteúdos. Assim será possível dar lugar a um discurso pedagógico que inclua os vários intervenientes no processo de aprendizagem e a construção de conhecimento, num espaço de interação suportado pela tecnologia

Quando todos os caminhos levavam a Portugal:impacto da guerra dos cem anos na vida económica e política de Portugal (séculos XIV-XV)

Tese de doutoramento, História (História Medieval), Universidade de Lisboa, Faculdade de Letras, 2014