GSVA: gene set variation analysis for microarray and RNA-seq data

Gene set enrichment (GSE) analysis is a popular framework for condensing information from gene expression profiles into a pathway or signature summary. The strengths of this approach over single gene analysis include noise and dimension reduction, as well as greater biological interpretability. As molecular profiling experiments move beyond simple case-control studies, robust and flexible GSE methodologies are needed that can model pathway activity within highly heterogeneous data sets. To address this challenge, we introduce Gene Set Variation Analysis (GSVA), a GSE method that estimates variation of pathway activity over a sample population in an unsupervised manner. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in differential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments. GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded at http://www.bioconductor.org.

Identification of molecular subtypes and gene expression patterns of breast cancer analysing RNA-seq data

Breast cancer is the most common diagnosed cancer and the leading cause of cancer death among females worldwide. It is considered a highly heterogeneous disease and it must be classified into more homogeneous groups. Hence, the purpose of this study was to classify breast tumors based on variations in gene expression patterns derived from RNA sequencing by using different class discovery methods. 42 breast tumors paired-samples were sequenced by Illumine Genome Analyzer and the data was analyzed and prepared by TopHat2 and htseq-count. As reported previously, breast cancer could be grouped into five main groups known as basal epithelial-like group, HER2 group, normal breast-like group and two Luminal groups with a distinctive expression profile. Classifying breast tumor samples by using PAM50 method, the most common subtype was Luminal B and was significantly associated with ESR1 and ERBB2 high expression. Luminal A subtype had ESR1 and SLC39A6 significant high expression, whereas HER2 subtype had a high expression of ERBB2 and CNNE1 genes and low luminal epithelial gene expression. Basal-like and normal-like subtypes were associated with low expression of ESR1, PgR and HER2, and had significant high expression of cytokeratins 5 and 17. Our results were similar compared with TGCA breast cancer data results and with known studies related with breast cancer classification. Classifying breast tumors could add significant prognostic and predictive information to standard parameters, and moreover, identify marker genes for each subtype to find a better therapy for patients with breast cancer.

Evidence for coseismic events of recurrent prehistoric deformation along the Alhama de Murcia fault, southeastern Spain

The Alhama de Murcia fault is a 85 km long oblique-slip fault, and is related to historical and instrumental seismic activity. A paleoseismic analysis of the Lorca-Totana sector of the fault containing MSK I=VIII historical earthquakes was made in order to identify and quantify its seismic potential. We present 1) the results of the neotectonic, structural and geomorphological analyses and, 2) the results of trenching. In the study area, the Alhama de Murcia fault forms a depressed corridor between two strands, the northwestern fault with morphological and structural features of a reverse component of slip, bounding the La Tercia range to the South, and the southeastern fault strand with evidence of sinistral oblique strike-slip movement. The offset along this latter fault trapped the sediments in transit from the La Tercia range towards the Guadalentín depression. The most recent of these sediments are arranged in three generations of alluvial fans and terraces. The first two trenches were dug in the most recent sediments across the southeastern fault strand. The results indicate a coseismic reverse fault deformation that involved the sedimentary sequence up to the intermediate alluvial fan and the Holocene terrace deposits. The sedimentary evolution observed in the trenches suggests an event of temporary damming of the Colmenar creek drainage to the South due to uplifting of the hanging wall during coseismic activation of the fault. Trench, structural and sedimentological features provide evidence of at least three coseismic events, which occurred after 125,000 yr. The minimum vertical slip rate along the fault is 0.06 mm/yr and the average recurrence period should not exceed 40,000 yr in accordance with the results obtained by fan topographic profiling. Further absolute dating is ongoing to constrain these estimates.

Políticas de encaminamiento tolerantes a fallos

El uso intensivo y prolongado de computadores de altas prestaciones para ejecutar aplicaciones computacionalmente intensivas, sumado al elevado número de elementos que los componen, incrementan drásticamente la probabilidad de ocurrencia de fallos durante su funcionamiento. El objetivo del trabajo es resolver el problema de tolerancia a fallos para redes de interconexión de altas prestaciones, partiendo del diseño de polí­ticas de encaminamiento tolerantes a fallos. Buscamos resolver una determinada cantidad de fallos de enlaces y nodos, considerando sus factores de impacto y probabilidad de aparición. Para ello aprovechamos la redundancia de caminos de comunicación existentes, partiendo desde enfoques de encaminamiento adaptativos capaces de cumplir con las cuatro fases de la tolerancia a fallos: detección del error, contención del daño, recuperación del error, y tratamiento del fallo y continuidad del servicio. La experimentación muestra una degradación de prestaciones menor al 5%. En el futuro, se tratará la pérdida de información en tránsito.

Effect of magnesium sulphate and L-tryptophan and genotype on the feed intake, behaviour and meat quality of pigs

Sixty-nine entire male pigs with different halothane genotype (homozygous halothane positive – nn –, n=36; and homozygous halothane negative – NN-, n=33) were fed with a supplementation of magnesium sulphate (Mg) and/or L-tryptophan (Trp) in the diet for 5 days before slaughter. Animals were housed individually and were submitted to stressful ante mortem conditions (mixed in the lorry according to treatments and transported 1 hour on rough roads). Individual feed intake was recorded during the 5-d treatment. At the abattoir, pig behaviour was assessed in the raceway to the stunning system and during the stunning period by exposure to CO2. Muscle pH, colour, water holding capacity, texture and cathepsin activities were determined to assess meat quality. The number of pigs with an individual feed intake lower than 2 kg/d was significantly different among diets (P&0.05; Control: 8.7 %; Mg&Trp: 43.5 %; Trp: 17.4 %) and they were considered to have inadequate supplement intake. During the ante mortem period, 15.2 % of pigs included in the experiment died, and this percentage decreased to 8.7 % in those pigs with a feed intake & 2kg/day, all of them from the stress-sensitive pigs (nn). In general, no differences were observed in the behaviour of pigs along the corridor leading to the stunning system and inside the CO2 stunning system. During the stunning procedure, Trp diet showed shorter periods of muscular excitation than control and Mg&Trp diets. The combination of a stressful ante mortem treatment and Mg&Trp supplementation led to carcasses with high incidence of severe skin lesions. Different meat quality results were found when considering all pigs or considering only those with adequate supplement intake. In this later case, Trp increased pH45 (6.15) vs Control diet (5.96) in the Longissimus thoracis (LT) muscle (P&0.05) and pH at 24h (Trp: 5.59 vs C: 5.47) led to a higher incidence of dark, firm and exudative (DFD) traits in SM muscle (P&0.05). Genotype affected negatively all the meat quality traits. Seventy-five percent of LT and 60.0 % of the SM muscles from nn pigs were classified as pale, soft and exudative (PSE), while none of the NN pigs showed these traits (P&0.0001). No significant differences were found between genotypes on the incidence of DFD meat. Due to the negative effects observed in the Mg&Trp group in feed intake and carcass quality, the utilization of a mixture of magnesium sulphate and tryptophan is not recommended.

A linear optimization technique for graph pebbling

Graph pebbling is a network model for studying whether or not a given supply of discrete pebbles can satisfy a given demand via pebbling moves. A pebbling move across an edge of a graph takes two pebbles from one endpoint and places one pebble at the other endpoint; the other pebble is lost in transit as a toll. It has been shown that deciding whether a supply can meet a demand on a graph is NP-complete. The pebbling number of a graph is the smallest t such that every supply of t pebbles can satisfy every demand of one pebble. Deciding if the pebbling number is at most k is NP 2 -complete. In this paper we develop a tool, called theWeight Function Lemma, for computing upper bounds and sometimes exact values for pebbling numbers with the assistance of linear optimization. With this tool we are able to calculate the pebbling numbers of much larger graphs than in previous algorithms, and much more quickly as well. We also obtain results for many families of graphs, in many cases by hand, with much simpler and remarkably shorter proofs than given in previously existing arguments (certificates typically of size at most the number of vertices times the maximum degree), especially for highly symmetric graphs. Here we apply theWeight Function Lemma to several specific graphs, including the Petersen, Lemke, 4th weak Bruhat, Lemke squared, and two random graphs, as well as to a number of infinite families of graphs, such as trees, cycles, graph powers of cycles, cubes, and some generalized Petersen and Coxeter graphs. This partly answers a question of Pachter, et al., by computing the pebbling exponent of cycles to within an asymptotically small range. It is conceivable that this method yields an approximation algorithm for graph pebbling.

Els delictes contra la seguretat viària: aspectes substantius, processals i criminològics

Les infraccions penals en matèria de seguretat viària constitueixen un dels grups delictius que més interès teòric i pràctic han despertat en la doctrina i la jurisprudència. Per aquest motiu, al llarg de la recerca s'ha dut a terme l'anàlisi dels diferents il·lícits penals des d'una perspectiva interdisciplinar i transversal on no tan sols han tingut cabuda les reflexions teòriques i pràctiques sobre els arts. 379 i ss. CP, sinó també la valoració dels problemes processals i criminològics que són propis d'aquests fets justiciables que es vinculen amb la seguretat viària

WMR navigation using local potential field corridors and narrow local occupancy grid perception

Path planning and control strategies applied to autonomous mobile robots should fulfil safety rules as well as achieve final goals. Trajectory planning applications should be fast and flexible to allow real time implementations as well as environment interactions. The methodology presented uses the on robot information as the meaningful data necessary to plan a narrow passage by using a corridor based on attraction potential fields that approaches the mobile robot to the final desired configuration. It employs local and dense occupancy grid perception to avoid collisions. The key goals of this research project are computational simplicity as well as the possibility of integrating this method with other methods reported by the research community. Another important aspect of this work consist in testing the proposed method by using a mobile robot with a perception system composed of a monocular camera and odometers placed on the two wheels of the differential driven motion system. Hence, visual data are used as a local horizon of perception in which trajectories without collisions are computed by satisfying final goal approaches and safety criteria

Estudi de la mobilitat en diferents xarxes de transport públic

Aquest projecte es centra en la realització d’un estudi de la mobilitat en diferents xarxes de transport públic. En particular, aquest estudi pretén ser una anàlisi comparativa de conceptes relacionats amb la topologia i navegabilitat de xarxes de metro de diferents països des d’un punt de vista innovador, tot realitzant una aproximació interdisciplinària a l’anàlisi de les xarxes.Es tracta d’un estudi centrat sobretot en conceptes i mètodes desenvolupats últimament en el camps de les Xarxes Complexes i de la Teoria de la Informació. Això ens ha permès focalitzar les nostres conclusions en les mesures de navegabilitat de les diferents xarxes així com en els paràmetres topològics que ens les defineixen, sense basar-nos en dades geogràfiques ni operatives. Els sistemes de metro estudiats en el present treball són els de Barcelona, Moscou, París i Nova York. Són sistemes que s’han desenvolupat en ambients històrics i culturals molt diversos fet que pot donar lloc a veure si aquesta circumstància és causant de diferències estructurals i de funcionament entre ells o bési pel contrari segueixen uns patrons de comportament semblants

How effective are policies to reduce gasoline consumption? evaluating a quasi-natural experiment in Spain

Using a panel of 48 provinces for four years we empirically analyze a series of temporary policies aimed at curbing fuel consumption implemented in Spain between March and June 2011. The first policy was a reduction in the speed limit in highways. The second policy was an increase in the biofuel content of fuels used in the transport sector. The third measure was a reduction of 5% in commuting and regional train fares that resulted in two major metropolitan areas reducing their overall fare for public transit. The results indicate that the speed limit reduction in highways reduced gasoline consumption by between 2% and 3%, while an increase in the biofuel content of gasoline increased this consumption. This last result is consistent with experimental evidence that indicates that mileage per liter falls with an increase in the biofuel content in gasolines. As for the reduction in transit fares, we do not find a significant effect for this policy. However, in specifications including the urban transit fare for the major cities in each province the estimated cross-price elasticity of the demand for gasoline -used as a proxy for car use- with respect to the price of transit is within the range reported in the literature. This is important since one of the main eficiency justification for subsidizing public transit rests on the positive value of this parameter and most of the estimates reported in the literature are quite dated.

Theorizing institutional changes: understanding decentralization and federalization in Brazil, Spain and South Africa

In light of the existing theories about institutional change, this paper seeks to advance a common framework to understand the unfolding of decentralization and federalization in three countries: Brazil, Spain, and South Africa. Although in different continents, these three countries witnessed processes after their respective transitions to democracy that transferred administrative and fiscal authority to their regions (decentralization) and vertically distributed political and institutional capacity (federalization). This paper attempts to explain how institutional changes prompted a shift of power and authority towards regional governments by looking at internal sources of change within the intergovernmental arena in the three countries. This analysis is organized around two propositions: that once countries transit to democracy under all-encompassing constitutions there are high incentives for institutional change, and that under a bargained intergovernmental interaction among political actors subnational political elites are able to advance their interests incrementally. In short, through a common framework this paper will explain the evolving dynamics of intergovernmental dynamics in three countries.

Anomalous crossover between thermal and shot noise in macroscopic diffusive conductors

We predict the existence of an anomalous crossover between thermal and shot noise in macroscopic diffusive conductors. We first show that, besides thermal noise, these systems may also exhibit shot noise due to fluctuations of the total number of carriers in the system. Then we show that at increasing currents the crossover between the two noise behaviors is anomalous, in the sense that the low-frequency current spectral density displays a region with a superlinear dependence on the current up to a cubic law. The anomaly is due to the nontrivial coupling in the presence of the long-range Coulomb interaction among the three time scales relevant to the phenomenon, namely, diffusion, transit, and dielectric relaxation time.

Shot noise anomalies in elastic nondegenerate diffusive conductors

We present a theoretical investigation of shot-noise properties in nondegenerate elastic diffusive conductors. Both Monte Carlo simulations and analytical approaches are used. Two interesting phenomena are found: (i) the display of enhanced shot noise for given energy dependences of the scattering time, and (ii) the recovery of full shot noise for asymptotic high applied bias. The first phenomenon is associated with the onset of negative differential conductivity in energy space that drives the system towards a dynamical electrical instability in excellent agreement with analytical predictions. The enhancement is found to be strongly amplified when the dimensionality in momentum space is lowered from three to two dimensions. The second phenomenon is due to the suppression of the effects of long-range Coulomb correlations that takes place when the transit time becomes the shortest time scale in the system, and is common to both elastic and inelastic nondegenerate diffusive conductors. These phenomena shed different light in the understanding of the anomalous behavior of shot noise in mesoscopic conductors, which is a signature of correlations among different current pulses.

Shot noise in linear macroscopic resistors

We report on direct experimental evidence of shot noise in a linear macroscopic resistor. The origin of the shot noise comes from the fluctuation of the total number of charge carriers inside the resistor associated with their diffusive motion under the condition that the dielectric relaxation time becomes longer than the dynamic transit time. The present results show that neither potential barriers nor the absence of inelastic scattering are necessary to observe shot noise in electronic devices.

dKDM5/LID regulates H3K4me3 dynamics at the transcription-start site (TSS) of actively transcribed developmental genes

H3K4me3 is a histone modification that accumulates at the transcription-start site (TSS) of active genes and is known to be important for transcription activation. The way in which H3K4me3 is regulated at TSS and the actual molecular basis of its contribution to transcription remain largely unanswered. To address these questions, we have analyzed the contribution of dKDM5/LID, the main H3K4me3 demethylase in Drosophila, to the regulation of the pattern of H3K4me3. ChIP-seq results show that, at developmental genes, dKDM5/LID localizes at TSS and regulates H3K4me3. dKDM5/LID target genes are highly transcribed and enriched in active RNApol II and H3K36me3, suggesting a positive contribution to transcription. Expression-profiling show that, though weakly, dKDM5/LID target genes are significantly downregulated upon dKDM5/LID depletion. Furthermore, dKDM5/LID depletion results in decreased RNApol II occupancy, particularly by the promoter-proximal Pol lloser5 form. Our results also show that ASH2, an evolutionarily conserved factor that locates at TSS and is required for H3K4me3, binds and positively regulates dKDM5/LID target genes. However, dKDM5/LID and ASH2 do not bind simultaneously and recognize different chromatin states, enriched in H3K4me3 and not, respectively. These results indicate that, at developmental genes, dKDM5/LID and ASH2 coordinately regulate H3K4me3 at TSS and that this dynamic regulation contributes to transcription.