Generation of biological association networks: A novel strategy to detect new targets in cancer therapy

The aim of this work was to design a novel strategy to detect new targets for anticancer treatments. The rationale was to build Biological Association Networks from differentially expressed genes in drug-resistant cells to identify important nodes within the Networks. These nodes may represent putative targets to attack in cancer therapy, as a way to destabilize the gene network developed by the resistant cells to escape from the drug pressure. As a model we used cells resistant to methotrexate (MTX), an inhibitor of DHFR. Selected node-genes were analyzed at the transcriptional level and from a genotypic point of view. In colon cancer cells, DHFR, the AKR1 family, PKC¿, S100A4, DKK1, and CAV1 were overexpressed while E-cadherin was lost. In breast cancer cells, the UGT1A family was overexpressed, whereas EEF1A1 was overexpressed in pancreatic cells. Interference RNAs directed against these targets sensitized cells towards MTX.

"Next-generation" Sequencing (NGS): The new genomic revolution

In the past 5 years "Next-generation" Sequencing (NGS) technologies have transformed genomics by delivering fast, inexpensive and accurate genomeinformation changing the way we think about scientific approaches in basic,applied and clinical research. The inexpensive production of large volumes ofsequence data is the main advantage over the automated Sanger method,making this new technology useful for many applications. In this chapter, a brieftechnical review of NGS technologies is given, along with the keys to NGSsuccess and a broad range of applications for NGS technologies.

Learning form Nature to improve the heat generation of iron-oxide nanoparticles for magnetic hyperthermia applications.

The performance of magnetic nanoparticles is intimately entwined with their structure, mean size and magnetic anisotropy. Besides, ensembles offer a unique way of engineering the magnetic response by modifying the strength of the dipolar interactions between particles. Here we report on an experimental and theoretical analysis of magnetic hyperthermia, a rapidly developing technique in medical research and oncology. Experimentally, we demonstrate that single-domain cubic iron oxide particles resembling bacterial magnetosomes have superior magnetic heating efficiency compared to spherical particles of similar sizes. Monte Carlo simulations at the atomic level corroborate the larger anisotropy of the cubic particles in comparison with the spherical ones, thus evidencing the beneficial role of surface anisotropy in the improved heating power. Moreover we establish a quantitative link between the particle assembling, the interactions and the heating properties. This knowledge opens new perspectives for improved hyperthermia, an alternative to conventional cancer therapies.

Generation and nonlinear evolution of shore-oblique/transverse sand bars

The coupling between topography, waves and currents in the surf zone may selforganize to produce the formation of shore-transverse or shore-oblique sand bars on an otherwise alongshore uniform beach. In the absence of shore-parallel bars, this has been shown by previous studies of linear stability analysis, but is now extended to the finite-amplitude regime. To this end, a nonlinear model coupling wave transformation and breaking, a shallow-water equations solver, sediment transport and bed updating is developed. The sediment flux consists of a stirring factor multiplied by the depthaveraged current plus a downslope correction. It is found that the cross-shore profile of the ratio of stirring factor to water depth together with the wave incidence angle primarily determine the shape and the type of bars, either transverse or oblique to the shore. In the latter case, they can open an acute angle against the current (upcurrent oriented) or with the current (down-current oriented). At the initial stages of development, both the intensity of the instability which is responsible for the formation of the bars and the damping due to downslope transport grow at a similar rate with bar amplitude, the former being somewhat stronger. As bars keep on growing, their finite-amplitude shape either enhances downslope transport or weakens the instability mechanism so that an equilibrium between both opposing tendencies occurs, leading to a final saturated amplitude. The overall shape of the saturated bars in plan view is similar to that of the small-amplitude ones. However, the final spacings may be up to a factor of 2 larger and final celerities can also be about a factor of 2 smaller or larger. In the case of alongshore migrating bars, the asymmetry of the longshore sections, the lee being steeper than the stoss, is well reproduced. Complex dynamics with merging and splitting of individual bars sometimes occur. Finally, in the case of shore-normal incidence the rip currents in the troughs between the bars are jet-like while the onshore return flow is wider and weaker as is observed in nature.

Generation of symmetric periodic orbits by a heteroclinic loop formed by two singular points and their invariant manifolds of dimension 1 and 2 in R3

In this paper we will find a continuous of periodic orbits passing near infinity for a class of polynomial vector fields in R3. We consider polynomial vector fields that are invariant under a symmetry with respect to a plane and that possess a “generalized heteroclinic loop” formed by two singular points e+ and e− at infinity and their invariant manifolds � and . � is an invariant manifold of dimension 1 formed by an orbit going from e− to e+, � is contained in R3 and is transversal to . is an invariant manifold of dimension 2 at infinity. In fact, is the 2–dimensional sphere at infinity in the Poincar´e compactification minus the singular points e+ and e−. The main tool for proving the existence of such periodic orbits is the construction of a Poincar´e map along the generalized heteroclinic loop together with the symmetry with respect to .

Plagiarism meets paraphrasing: insights for the new generation in automatic plagiarism detection

Although paraphrasing is the linguistic mechanism underlying many plagiarism cases, little attention has been paid to its analysis in the framework of automatic plagiarism detection. Therefore, state-of-the-art plagiarism detectors find it difficult to detect cases of paraphrase plagiarism. In this article, we analyse the relationship between paraphrasing and plagiarism, paying special attention to which paraphrase phenomena underlie acts of plagiarism and which of them are detected by plagiarism detection systems. With this aim in mind, we created the P4P corpus, a new resource which uses a paraphrase typology to annotate a subset of the PAN-PC-10 corpus for automatic plagiarism detection. The results of the Second International Competition on Plagiarism Detection were analysed in the light of this annotation. The presented experiments show that (i) more complex paraphrase phenomena and a high density of paraphrase mechanisms make plagiarism detection more difficult, (ii) lexical substitutions are the paraphrase mechanisms used the most when plagiarising, and (iii) paraphrase mechanisms tend to shorten the plagiarized text. For the first time, the paraphrase mechanisms behind plagiarism have been analysed, providing critical insights for the improvement of automatic plagiarism detection systems.

Vegetative and reproductive morphology of Kallymenia patens (Kallymeniaceae, Rhodophyta) in the Mediterranean Sea

Reproductive morphology of the Mediterranean red alga Kallymenia patens is described for the first time, confirming its position in the genus. K. patens is characterized by a non-procarpic female reproductive apparatus, carpogonial branch systems consisting of supporting cells bearing both three-celled carpogonial branches and subsidiary cells that lack a hypogynous cell and carpogonium; fusion cells develop numerous connecting filaments, and tetrasporangia are scattered over the thallus and are probably cruciately divided. Old fertile spathulate specimens of K. patens are morphologically similar to K. spathulata, but they can be distinguished by the length of spathulated proliferations (up to 0.6 cm and 6 cm, respectively), the length of inner cortical cells (up to 70 and 30 μm, respectively), and the gonimoblast location (in proliferations from the perennial part of the blade and over all the thallus surface, respectively)

Beyond the Net Generation debate: A comparison between digital learners in face-to-face and virtual universities

This paper is based on the hypothesis that the use of technology to support learning is not related to whether a student belongs to the Net Generation, but that it is mainly influenced by the teaching model. The study compares behaviour and preferences towards ICT use in two groups of university students: face-to-face students and online students. A questionnaire was applied to asample of students from five universities with different characteristics (one offers online education and four offer face-to-face education with LMS teaching support).

Report on theorerical results of power generation and conversion

Experimental results of a new controller able to support bidirectional power flow in a full-bridge rectifier with boost-like topology are obtained. The controller is computed using port Hamiltonian passivity techniques for a suitable generalized state space averaging truncation system, which transforms the control objectives, namely constant output voltage dc-bus and unity input power factor, into a regulation problem. Simulation results for the full system show the essential correctness of the simplifications introduced to obtain the controller, although some small experimental discrepancies point to several aspects that need further improvement.

Effect of growth selection on morphology in Pirenaica cattle

Twelve variables were identified to define morphology in 109 calves sired by eight Pirenaica bulls widely used in artificial insemination. The effect of selection for weight at 210 days of age (W210) was detected from the regression coefficient between the 12 variables and the selection index for W210 used in the breeding plan. Unbiased estimates of the genetic correlated responses on the morphology were obtained without previously estimating the genetic correlation among traits. In Pirenaica cattle, selection for W210 increased slaughter live weight, chest depth and corporal length. The expected changes on height (withers, back and rump), rump width and thoracic perimeter were lower but positive and statistically significant.

Seedling development and biomass as affected by seed size and morphology in durum wheat

This work evaluated the effect of seed size and morphology on the development and biomass of durum wheat seedlings. Three different seed-grading sizes selected by sieving were used in glasshouse experiments, and a set of three developmental and 23 biomass-related indices were measured on eight genotypes, at two moisture levels. The influence of seed size on seedling development was studied at high and low temperatures (22\12 mC, and 15\5 mC day\night temperatures, respectively), in growth chambers. The area of the seed and the area of the embryo were the seed morphological traits most affected by seed size. Seed size was strongly associated with seedling development and seedling biomass until the complete extension of the first two leaves, at the fourth leaf stage. The rate of first-leaf growth and the area of the first leaf were the developmental and biomass traits, respectively, most sensitive to seed-grading size.

Collaborative explicit plasticity framework: a conceptual scheme for the generation of plastic and group-aware user interfaces

The advent of new advances in mobile computing has changed the manner we do our daily work, even enabling us to perform collaborative activities. However, current groupware approaches do not offer an integrating and efficient solution that jointly tackles the flexibility and heterogeneity inherent to mobility as well as the awareness aspects intrinsic to collaborative environments. Issues related to the diversity of contexts of use are collected under the term plasticity. A great amount of tools have emerged offering a solution to some of these issues, although always focused on individual scenarios. We are working on reusing and specializing some already existing plasticity tools to the groupware design. The aim is to offer the benefits from plasticity and awareness jointly, trying to reach a real collaboration and a deeper understanding of multi-environment groupware scenarios. In particular, this paper presents a conceptual framework aimed at being a reference for the generation of plastic User Interfaces for collaborative environments in a systematic and comprehensive way. Starting from a previous conceptual framework for individual environments, inspired on the model-based approach, we introduce specific components and considerations related to groupware.

The changing milliarcsecond radio morphology of the gamma-ray binary LS 5039

LS 5039 is one of the few TeV emitting X-ray binaries detected so far. The powering source of its multiwavelength emission can be accretion in a microquasar scenario or wind interaction in a young nonaccreting pulsar scenario. Aims.To present new high-resolution radio images and compare them with the expected behavior in the different scenarios. Methods.We analyze Very Long Baseline Array (VLBA) radio observations that provide morphological and astrometric information at milliarcsecond scales. Results.We detect a changing morphology between two images obtained five days apart. In both runs there is a core component with a constant flux density, and an elongated emission with a position angle (PA) that changes by 12 $\pm$ $3\degr$ between both runs. The source is nearly symmetric in the first run and asymmetric in the second one. The astrometric results are not conclusive. Conclusions.A simple and shockless microquasar scenario cannot easily explain the observed changes in morphology. An interpretation within the young nonaccreting pulsar scenario requires the inclination of the binary system to be very close to the upper limit imposed by the absence of X-ray eclipses.

GD3 Synthase Overexpression Sensitizes Hepatocarcinoma Cells to Hypoxia and Reduces Tumor Growth by Suppressing the cSrc/NF-κB Survival Pathway

Abstract Background: Hypoxia-mediated HIF-1a stabilization and NF-kB activation play a key role in carcinogenesis by fostering cancer cell survival, angiogenesis and tumor invasion. Gangliosides are integral components of biological membranes with an increasingly recognized role as signaling intermediates. In particular, ganglioside GD3 has been characterized as a proapoptotic lipid effector by promoting cell death signaling and suppression of survival pathways. Thus, our aim was to analyze the role of GD3 in hypoxia susceptibility of hepatocarcinoma cells and in vivo tumor growth. Methodology/Principal Findings: We generated and characterized a human hepatocarcinoma cell line stably expressing GD3 synthase (Hep3B-GD3), which catalyzes the synthesis of GD3 from GM3. Despite increased GD3 levels (2-3 fold), no significant changes in cell morphology or growth were observed in Hep3B-GD3 cells compared to wild type Hep3B cells under normoxia. However, exposure of Hep3B-GD3 cells to hypoxia (2% O2) enhanced reactive oxygen species (ROS) generation, resulting in decreased cell survival, with similar findings observed in Hep3B cells exposed to increasing doses of exogenous GD3. In addition, hypoxia-induced c-Src phosphorylation at tyrosine residues, NF-kB activation and subsequent expression of Mn-SOD were observed in Hep3B cells but not in Hep3B-GD3 cells. Moreover, MnTBAP, an antioxidant with predominant SOD mimetic activity, reduced ROS generation, protecting Hep3B-GD3 cells from hypoxia-induced death. Finally, lower tumor growth, higher cell death and reduced Mn-SOD expression were observed in Hep3B-GD3 compared to Hep3B tumor xenografts. Conclusion: These findings underscore a role for GD3 in hypoxia susceptibility by disabling the c-Src/NF-kB survival pathway resulting in lower Mn-SOD expression, which may be of relevance in hepatocellular carcinoma therapy.

Reproductive morphology in Mediterranean Seirospora giraudyi (Ceramiales, Rhodophyta)

This paper presents a detailed description of the reproductive characters of Mediterranean Seirospora giraudyi based on fresh material collected in the northwestern coast of Spain. Vegetative cells are uninucleate. The plant is monoecious. Spermantangial parent’s cells are clustered on modified dwarf determinate filaments, usually situated on adaxial surfaces of branches. One to four spermatia are formed by elongation and proximal divisions of the spermatangial parent cells. Spermatium with a nucleus situated ina mec. The thallus is procarpic. The four-celled carpogonial branch is initially L-shaped, and it is situated on a periaxial supporting fertile axial cell. The mature carpogonial branch is U-shaped and the supporting cell and second periaxial cell enlarge and divide transversely to reproduce a pair uninicleate auxiliary cell. The nucleus in the ferlilized carpogonium divides twice and the carpogonium cleaves vertically into two cells that, turn, cut off a pair of uninucleate connecting cells that fuse with the auxiliary cells on opposite sides; the diploid nuclei in the connecting cells divide at the site of fusion and one of the nuclei enters the auxiliary cell white the other is extruded. Each auxiliary cell gives to a terminal primary gonimolobe initials. Gonimolobes form lax chains of carposporangia. As the gonimoblasts mature, both lobes of the foot cell which is situated on the supporting cell elongate the upper one secondary connecting with the supporting cell, and the lower one with the fertile axial cell. The gonimoblasts are subtended at maturity by one to several clusters of involucral flaments. Seirospora is currently placed in the tribe Euptiloteae; however the reproductive character of S.giraudyi is dentical to those described for the Cañllithamnieae. Molecular studies are needed to confirm the taxonomic position of S.giraudyi as well as that of the other species placed Seirospora