Simcluster: clustering enumeration gene expression data on the simplex space

Abstract Background Transcript enumeration methods such as SAGE, MPSS, and sequencing-by-synthesis EST "digital northern", are important high-throughput techniques for digital gene expression measurement. As other counting or voting processes, these measurements constitute compositional data exhibiting properties particular to the simplex space where the summation of the components is constrained. These properties are not present on regular Euclidean spaces, on which hybridization-based microarray data is often modeled. Therefore, pattern recognition methods commonly used for microarray data analysis may be non-informative for the data generated by transcript enumeration techniques since they ignore certain fundamental properties of this space. Results Here we present a software tool, Simcluster, designed to perform clustering analysis for data on the simplex space. We present Simcluster as a stand-alone command-line C package and as a user-friendly on-line tool. Both versions are available at: http://xerad.systemsbiology.net/simcluster. Conclusion Simcluster is designed in accordance with a well-established mathematical framework for compositional data analysis, which provides principled procedures for dealing with the simplex space, and is thus applicable in a number of contexts, including enumeration-based gene expression data.

SAG2A protein from Toxoplasma gondii interacts with both innate and adaptive immune compartments of infected hosts

Abstract Background Toxoplasma gondii is an intracellular parasite that causes relevant clinical disease in humans and animals. Several studies have been performed in order to understand the interactions between proteins of the parasite and host cells. SAG2A is a 22 kDa protein that is mainly found in the surface of tachyzoites. In the present work, our aim was to correlate the predicted three-dimensional structure of this protein with the immune system of infected hosts. Methods To accomplish our goals, we performed in silico analysis of the amino acid sequence of SAG2A, correlating the predictions with in vitro stimulation of antigen presenting cells and serological assays. Results Structure modeling predicts that SAG2A protein possesses an unfolded C-terminal end, which varies its conformation within distinct strain types of T. gondii. This structure within the protein shelters a known B-cell immunodominant epitope, which presents low identity with its closest phyllogenetically related protein, an orthologue predicted in Neospora caninum. In agreement with the in silico observations, sera of known T. gondii infected mice and goats recognized recombinant SAG2A, whereas no serological cross-reactivity was observed with samples from N. caninum animals. Additionally, the C-terminal end of the protein was able to down-modulate pro-inflammatory responses of activated macrophages and dendritic cells. Conclusions Altogether, we demonstrate herein that recombinant SAG2A protein from T. gondii is immunologically relevant in the host-parasite interface and may be targeted in therapeutic and diagnostic procedures designed against the infection.

Functional clustering of time series gene expression data by Granger causality

Background: A common approach for time series gene expression data analysis includes the clustering of genes with similar expression patterns throughout time. Clustered gene expression profiles point to the joint contribution of groups of genes to a particular cellular process. However, since genes belong to intricate networks, other features, besides comparable expression patterns, should provide additional information for the identification of functionally similar genes. Results: In this study we perform gene clustering through the identification of Granger causality between and within sets of time series gene expression data. Granger causality is based on the idea that the cause of an event cannot come after its consequence. Conclusions: This kind of analysis can be used as a complementary approach for functional clustering, wherein genes would be clustered not solely based on their expression similarity but on their topological proximity built according to the intensity of Granger causality among them.

Frequency and precision of feedback and the adaptive process of learning a dual motor task

This work investigated the effects of frequency and precision of feedback on the learning of a dual-motor task. One hundred and twenty adults were randomly assigned to six groups of different knowledge of results (KR), frequency (100%, 66% or 33%) and precision (specific or general) levels. In the stabilization phase, participants performed the dual task (combination of linear positioning and manual force control) with the provision of KR. Ten non-KR adaptation trials were performed for the same task, but with the introduction of an electromagnetic opposite traction force. The analysis showed a significant main effect for frequency of KR. The participants who received KR in 66% of the stabilization trials showed superior adaptation performance than those who received 100% or 33%. This finding reinforces that there is an optimal level of information, neither too high nor too low, for motor learning to be effective.

Cementum, apical morphology and hypercementosis: a probable adaptive response of the periodontal support tissues and potential orthodontic implications

Information about orthodontic movement of teeth with hypercementosis is scarce. As cementum deposition continues to occur, cementum is expected to change the shape of the root and apex over time, but this has not yet been demonstrated. Nor has it ever been established whether it increases or decreases the prevalence of root resorption during orthodontic treatment. The unique biological function of the interconnected network of cementocytes may play a role in orthodontic movement and its associated root resorptions, but no research has ever been conducted on the topic. Unlike cementum thickness and hypercementosis, root and apex shape has not yet been related to patient age. A study of the precise difference between increased cementum thickness and hypercementosis is warranted. Hypercementosis refers to excessive cementum formation above and beyond the extent necessary to fulfill its normal functions, resulting in abnormal thickening with macroscopic changes in the tooth root, which may require the delivery of forces that are different from conventional mechanics in their intensity, direction and distribution. What are the unique features and specificities involved in moving teeth that present with hypercementosis? Bodily movements would be expected to occur, since inclination might prove difficult to achieve, but would the root resorption index be higher or lower?

Adaptive immunity is related to coronary artery disease severity after acute coronary syndrome in subjects with metabolic syndrome

Metabolic syndrome (MetS) is an inflammatory state associated with high coronary disease risk. Inflammation and adaptive immunity modulate atherosclerosis and plaque instability. We examined early changes in anti-oxidized lowdensity lipoprotein (LDL) (anti-oxLDL) autoantibodies (Abs) in patients with MetS after an acute coronary syndrome (ACS). Patients of both genders (n=116) with MetS were prospectively included after an acute yocardial infarction (MI) or hospitalization due to unstable angina. Anti-oxLDL Abs (IgG class) were assayed at baseline, three and six weeks after ACS. The severity of coronary disease was evaluated by the Gensini score. We observed a decrease in anti-oxLDL Abs titers (p<0.002 vs. baseline), mainly in males (p=0.01), in those under 65 y (p=0.03), and in subjects with Gensini score above median (p=0.04). In conclusion, early decrease in circulating anti-oxLDL Abs is associated with coronary disease severity among subjects with MetS.

Dengue virus type 3 adaptive changes during epidemics in São Jose de Rio Preto, Brazil, 2006–2007

Global dengue virus spread in tropical and sub-tropical regions has become a major international public health concern. It is evident that DENV genetic diversity plays a significant role in the immunopathology of the disease and that the identification of polymorphisms associated with adaptive responses is important for vaccine development. The investigation of naturally occurring genomic variants may play an important role in the comprehension of different adaptive strategies used by these mutants to evade the human immune system. In order to elucidate this role we sequenced the complete polyprotein-coding region of thirty-three DENV-3 isolates to characterize variants circulating under high endemicity in the city of São José de Rio Preto, Brazil, during the onset of the 2006-07 epidemic. By inferring the evolutionary history on a local-scale and estimating rates of synonymous (dS) and nonsynonimous (dN) substitutions, we have documented at least two different introductions of DENV-3 into the city and detected 10 polymorphic codon sites under significant positive selection (dN/dS > 1) and 8 under significant purifying selection (dN/dS < 1). We found several polymorphic amino acid coding sites in the envelope (15), NS1 (17), NS2A (11), and NS5 (24) genes, which suggests that these genes may be experiencing relatively recent adaptive changes. Furthermore, some polymorphisms correlated with changes in the immunogenicity of several epitopes. Our study highlights the existence of significant and informative DENV variability at the spatio-temporal scale of an urban outbreak.

Human Abuses of Coral Reefs- Adaptive Responses and Regime Transitions

During the last few decades, coral reefs have become a disappearing feature of tropical marine environments, and those reefs that do remain are severely threatened. It is understood that humans have greately altered the environment under which these ecosystems previously have thrived and evoloved. Overharvesting of fish stocks, global warming and pollution are some of the most prominent threats, acting on coral reefs at several spatial and temporal scales. Presently, it is common that coral reefs have been degraded into alternative ecosystem regimes, such as macroalgae-dominated or sea urchin-barren. Although these ecosystems could potentially return to coral dominance in a long-term perspective, when considdering current conditions, it seems likely that they will persist in their degraded states. Thus, recovery of coral reefs cannot be taken for granted on a human timescale. Multiple stressors and disturbances, which are increasingly characteristic of coral reef environments today, are believed to act synergistically and produce ecological surprises. However, current knowledge of effects of compounded disturbances and stress is limited. Based on five papers, this thesis investigates the sublethal response of multiple stressors on coral physiology, as well as the effects of compounded stress and disturbance on coral reef structure and function. Adaptive responses to stress and disturbance in relation to prior experience are highlighted. The thesis further explores how inherent characteristics (traits) of corals and macroalgae may influence regime expression when faced with altered disturbance regimes, in particular overfishing, eutrophication, elevated temperature, and enhanced substrate availability. Finally, possibilities of affecting the resilience of macroalgae-dominaed reefs and shifting the community composition towards a coral-dominated regime are explored.

Clustering of variables around latent components: an application in consumer science

The present work proposes a method based on CLV (Clustering around Latent Variables) for identifying groups of consumers in L-shape data. This kind of datastructure is very common in consumer studies where a panel of consumers is asked to assess the global liking of a certain number of products and then, preference scores are arranged in a two-way table Y. External information on both products (physicalchemical description or sensory attributes) and consumers (socio-demographic background, purchase behaviours or consumption habits) may be available in a row descriptor matrix X and in a column descriptor matrix Z respectively. The aim of this method is to automatically provide a consumer segmentation where all the three matrices play an active role in the classification, getting homogeneous groups from all points of view: preference, products and consumer characteristics. The proposed clustering method is illustrated on data from preference studies on food products: juices based on berry fruits and traditional cheeses from Trentino. The hedonic ratings given by the consumer panel on the products under study were explained with respect to the product chemical compounds, sensory evaluation and consumer socio-demographic information, purchase behaviour and consumption habits.

Cross-layer optimizations in multi-hop ad hoc networks

Unlike traditional wireless networks, characterized by the presence of last-mile, static and reliable infrastructures, Mobile ad Hoc Networks (MANETs) are dynamically formed by collections of mobile and static terminals that exchange data by enabling each other's communication. Supporting multi-hop communication in a MANET is a challenging research area because it requires cooperation between different protocol layers (MAC, routing, transport). In particular, MAC and routing protocols could be considered mutually cooperative protocol layers. When a route is established, the exposed and hidden terminal problems at MAC layer may decrease the end-to-end performance proportionally with the length of each route. Conversely, the contention at MAC layer may cause a routing protocol to respond by initiating new routes queries and routing table updates. Multi-hop communication may also benefit the presence of pseudo-centralized virtual infrastructures obtained by grouping nodes into clusters. Clustering structures may facilitate the spatial reuse of resources by increasing the system capacity: at the same time, the clustering hierarchy may be used to coordinate transmissions events inside the network and to support intra-cluster routing schemes. Again, MAC and clustering protocols could be considered mutually cooperative protocol layers: the clustering scheme could support MAC layer coordination among nodes, by shifting the distributed MAC paradigm towards a pseudo-centralized MAC paradigm. On the other hand, the system benefits of the clustering scheme could be emphasized by the pseudo-centralized MAC layer with the support for differentiated access priorities and controlled contention. In this thesis, we propose cross-layer solutions involving joint design of MAC, clustering and routing protocols in MANETs. As main contribution, we study and analyze the integration of MAC and clustering schemes to support multi-hop communication in large-scale ad hoc networks. A novel clustering protocol, named Availability Clustering (AC), is defined under general nodes' heterogeneity assumptions in terms of connectivity, available energy and relative mobility. On this basis, we design and analyze a distributed and adaptive MAC protocol, named Differentiated Distributed Coordination Function (DDCF), whose focus is to implement adaptive access differentiation based on the node roles, which have been assigned by the upper-layer's clustering scheme. We extensively simulate the proposed clustering scheme by showing its effectiveness in dominating the network dynamics, under some stressing mobility models and different mobility rates. Based on these results, we propose a possible application of the cross-layer MAC+Clustering scheme to support the fast propagation of alert messages in a vehicular environment. At the same time, we investigate the integration of MAC and routing protocols in large scale multi-hop ad-hoc networks. A novel multipath routing scheme is proposed, by extending the AOMDV protocol with a novel load-balancing approach to concurrently distribute the traffic among the multiple paths. We also study the composition effect of a IEEE 802.11-based enhanced MAC forwarding mechanism called Fast Forward (FF), used to reduce the effects of self-contention among frames at the MAC layer. The protocol framework is modelled and extensively simulated for a large set of metrics and scenarios. For both the schemes, the simulation results reveal the benefits of the cross-layer MAC+routing and MAC+clustering approaches over single-layer solutions.

An adaptive solar radiation numerical model

[EN]A numerical model for the evaluation of solar radiation in different locations is presented. The solar radiation model is implemented taking into account the terrain surface using two-dimensional adaptive meshes of triangles that are constructed using a refinement/derefinement procedure in accordance with the variations of terrain surface and albedo. The selected methodology defines the terrain characteristics with a minimum number of points so that the computational cost is reduced for a given accuracy. The model can be used in atmospheric sciences as well as in other fields such as electrical engineering, since it allows the user to find the optimal location for maximum power generation in photovoltaic or solar thermal power plants...

Adaptive finite element simulation of stack pollutant emissions over complex terrains

[EN]A three-dimensional finite element model for the pollutant dispersion is presented. In these environmental processes over a complex terrain, a mesh generator capable of adapting itself to the topographic characteristics is essential. The first stage of the model consists on the construction of an adaptive tetrahedral mesh of a rectangular region bounded in its lower part by the terrain and in its upper part by a horizontal plane. Once the mesh is constructed, an adaptive local refinement of tetrahedra is used in order to capture the plume rise. Wind measurements are used to compute an interpolated wind field, that is modified by using a mass-consistent model and perturbing its vertical component to introduce the plume rise effect...