Optimization and Applications of Large-Scale Biomedical Event Networks

The overwhelming amount and unprecedented speed of publication in the biomedical domain make it difficult for life science researchers to acquire and maintain a broad view of the field and gather all information that would be relevant for their research. As a response to this problem, the BioNLP (Biomedical Natural Language Processing) community of researches has emerged and strives to assist life science researchers by developing modern natural language processing (NLP), information extraction (IE) and information retrieval (IR) methods that can be applied at large-scale, to scan the whole publicly available biomedical literature and extract and aggregate the information found within, while automatically normalizing the variability of natural language statements. Among different tasks, biomedical event extraction has received much attention within BioNLP community recently. Biomedical event extraction constitutes the identification of biological processes and interactions described in biomedical literature, and their representation as a set of recursive event structures. The 2009–2013 series of BioNLP Shared Tasks on Event Extraction have given raise to a number of event extraction systems, several of which have been applied at a large scale (the full set of PubMed abstracts and PubMed Central Open Access full text articles), leading to creation of massive biomedical event databases, each of which containing millions of events. Sinece top-ranking event extraction systems are based on machine-learning approach and are trained on the narrow-domain, carefully selected Shared Task training data, their performance drops when being faced with the topically highly varied PubMed and PubMed Central documents. Specifically, false-positive predictions by these systems lead to generation of incorrect biomolecular events which are spotted by the end-users. This thesis proposes a novel post-processing approach, utilizing a combination of supervised and unsupervised learning techniques, that can automatically identify and filter out a considerable proportion of incorrect events from large-scale event databases, thus increasing the general credibility of those databases. The second part of this thesis is dedicated to a system we developed for hypothesis generation from large-scale event databases, which is able to discover novel biomolecular interactions among genes/gene-products. We cast the hypothesis generation problem as a supervised network topology prediction, i.e predicting new edges in the network, as well as types and directions for these edges, utilizing a set of features that can be extracted from large biomedical event networks. Routine machine learning evaluation results, as well as manual evaluation results suggest that the problem is indeed learnable. This work won the Best Paper Award in The 5th International Symposium on Languages in Biology and Medicine (LBM 2013).

Modelling the Sun's small scale global photospheric magnetic field

We present a new model for the Sun's global photospheric magnetic field during a deep minimum of activity, in which no active regions emerge. The emergence and subsequent evolution of small- scale magnetic features across the full solar surface is simulated, subject to the influence of a global supergranular flow pattern. Visually, the resulting simulated magnetograms reproduce the typical structure and scale observed in quiet Sun magnetograms. Quantitatively, the simulation quickly reaches a steady state, resulting in a mean field and flux distribution that are in good agreement with those determined from observations. A potential coronal magnetic field is extrapolated from the simulated full Sun magnetograms, to consider the implications of such a quiet photospheric magnetic field on the corona and inner heliosphere. The bulk of the coronal magnetic field closes very low down, in short connections between small-scale features in the simulated magnetic network. Just 0.1% of the photospheric magnetic flux is found to be open at 2:5 Rʘ, around 10 - 100 times less than that determined for typical HMI synoptic map observations. If such conditions were to exist on the Sun, this would lead to a significantly weaker interplanetary magnetic field than is presently observed, and hence a much higher cosmic ray flux at Earth.

Ecological and evolutionary effects of dispersal on freshwater zooplankton

A recent focus on contemporary evolution and the connections between communities has sought to more closely integrate the fields of ecology and evolutionary biology. Studies of coevolutionary dynamics, life history evolution, and rapid local adaptation demonstrate that ecological circumstances can dictate evolutionary trajectories. Thus, variation in species identity, trait distributions, and genetic composition may be maintained among ecologically divergent habitats. New theories and hypotheses (e.g., metacommunity theory and the Monopolization hypothesis) have been developed to understand better the processes occurring in spatially structured environments and how the movement of individuals among habitats contributes to ecology and evolution at broader scales. As few empirical studies of these theories exist, this work seeks to further test these concepts. Spatial and temporal dispersal are the mechanisms that connect habitats to one another. Both processes allow organisms to leave conditions that are suboptimal or unfavorable, and enable colonization and invasion, species range expansion, and gene flow among populations. Freshwater zooplankton are aquatic crustaceans that typically develop resting stages as part of their life cycle. Their dormant propagules allow organisms to disperse both temporally and among habitats. Additionally, because a number of species are cyclically parthenogenetic, they make excellent model organisms for studying evolutionary questions in a controlled environment. Here, I use freshwater zooplankton communities as model systems to explore the mechanisms and consequences of dispersal and to test these nascent theories on the influence of spatial structure in natural systems. In Chapter one, I use field experiments and mathematical models to determine the range of adult zooplankton dispersal over land and what vectors are moving zooplankton. Chapter two focuses on prolonged dormancy of one aquatic zooplankter, Daphnia pulex. Using statistical models with field and mesocosm experiments, I show that variation in Daphnia dormant egg hatching is substantial among populations in nature, and some of that variation can be attributed to genetic differences among the populations. Chapters three and four explore the consequences of dispersal at multiple levels of biological organization. Chapter three seeks to understand the population level consequences of dispersal over evolutionary time on current patterns of population genetic differentiation. Nearby populations of D. pulex often exhibit high population genetic differentiation characteristic of very low dispersal. I explore two alternative hypotheses that seek to explain this pattern. Finally, chapter four is a case study of how dispersal has influenced patterns of variation at the community, trait and genetic levels of biodiversity in a lake metacommunity.

Small scale turbulence and mixing in semi-enclosed seas (Persian Gulf)

Turbulence and internal waves are probably important in generating layered structures in frontal region of marine environments (e.g. near river plumes outflow into the sea). Here we investigate the role of normal modes of internal waves in generation of layered structure in a part of Persian Gulf where river plume inters and in some laboratory experiments. The model prediction and observations show that layers so formed have a thickness of about 2m based on salinity variations with depth, but layers (about 5m) based on horizontal velocity profiles. Laboratory experiments with a plume outflow in a Filling Box profile also generate normal mode layered structure with 21H=0.5 (where A is layer thickness and H is the plume depth). In these experiments as Re of the flow is smaller than the Re of field flow. The normal modes are substantially dissipated with depth. Typical values of dissipation factor is about 0(100). This factor for field observation is 0(10) which is still substantial. Qualitative comparison between layered structure in field and laboratory is good. It should be emphasized that field observation is for semi-enclosed seas but the laboratory experiments are for enclosed region. Hence some of the discrepancies in the results of two cases are inevitable. Layered structures in marine environments are also produced by double diffusive convection. In this region this should be studied separately.

Investigations on growth ecology and reproduction of Sargassum sp. and Gracilaria on intertidal region in Bandar Lenge

Investigations on growth and quantity of phycocolloids of Sargassum sp. and Gracilaria corticata was done on field and laboratorial works over one year from January 2003 to May 2004. Sargassum thalli began growth from January. The highest biomass value recorded 1611.04 gm^-2 was obtained in November. The receptacles appeared on November and released eggs. The senescence of Sargassum thalli was in December and the new thallus began to grow from January, The highest relative growth rate (6.74 percent) was in February. The relative growth rate showed significant correlation (p<0,05) with temperature. The highest value of alginate was in November (10.02 percent). Alginat content showed significant correlations (p<0.05) with Sargassum biomass. There was no significant effect of environmental factors on alginate content. The highest biomass of Graciiaria was in Match (49.88 gm^-2). Maximum relative growth rate of Gracilara (2 percent) was in December. Relative growth rate of Gracilaria (2.8 percent) was in December. Relative growth rate of Gracilaria showed significant correlations (p<0.05) with temperature. There was significant effect of ammonium (p<0.05) on growth factors of Gracilaria, maximum agar content was in August {10.005 percent). The yield of agar showed significant correlation (p<0.05) with Gracilaria biomass and ammonium in field and laboratory.

Vegetables production in NW Portugal, agriculture practices and groundwater quality

In NW of Portugal, the region between Esposende and Vila do Conde was established into a unique system called masseiras; masseiras are small fields that were created at the beginning of XX century by removing sand from dunes. Since the 80’s sand between closed masseiras has been removed giving way for larger fields, the “enlarged masseira with greenhouses”. This region is part of vulnerable zone nº1 (VZ1). Nowadays, the masseiras have almost disappeared; they had been replaced by “enlarged masseiras with plastic greenhouses” exploited by a new generation of growers. As water quality is an indicator of agriculture practices, 8 wells were selected and water samples were collected on four dates from September 2009 to May 2010. Laboratorial analysis was performed on nitrates and 28 pesticides. The results confirm that water in VZ1 is contaminated with nitrates (as it was expected) and also with pesticides. The water was contaminated in both dug wells and drilled wells all year round. Masseiras’ wells have more nitrates than greenhouses’ wells, probably due to poor agricultural practices used by growers who still employ high quantities of fertilizers and water. Pesticides detected in water samples include some that have been sprayed in the field and others that have not. Some forbidden substances were found. Our results confirm that, in VZ1, there is a diffusion contamination, which origin is unknown. In this communication, we put in picture the history of masseiras fields: how masseiras fields have been created and how they have disappeared; what trends exist in pest management strategies and the use of fertilizers, pesticides and water resources. These results reinforce the need to change the agricultural system in this region of traditional vegetable production.

Universality of weakly bound dimers and Efimov trimers close to Li-Cs Feshbach resonances

We study the interspecies scattering properties of ultracold Li-Cs mixtures in their two energetically lowest spin channels in the magnetic field range between 800 and 1000 G. Close to two broad Feshbach resonances (FR) we create weakly bound LiCs dimers by radio-frequency association and measure the dependence of their binding energy on the external magnetic field strength. Based on the binding energies and complementary atom loss spectroscopy of three other Li-Cs s-wave FRs we construct precise molecular singlet and triplet electronic ground state potentials using a coupled-channels calculation. We extract the Li-Cs interspecies scattering length as a function of the external field and obtain almost a ten-fold improvement in the precision of the values for the pole positions and widths of the s-wave FRs as compared to our previous work (Pires et al 2014 Phys. Rev. Lett. 112 250404). We discuss implications on the Efimov scenario and the universal geometric scaling for LiCsCs trimers.

How does employer support and educational background effect an Ergonomics Practitioner’s awareness of the relationship between ergonomics and psychosocial hazard control?

There is a growning need to address psychological health and safety in the workplace. Ergonomics tends to be widely recognized for its physical applications, such as ¨office¨ and ¨manual materials handling¨ however the other domains of specialization of ergonomics (cognitive and organizational) appear to be less well known. This study evaluates the level of understanding that professionals who practice ergonomics have of the relation between ergonomics and the control of psychosocial hazards in the workplace. A survey was distributed to ergonomics practitioners and asked them about their awareness of the relation between ergonomics and workplace psychosocial hazard control. Ergonomists and human factors specialists demonstrated a greater awareness of this relationship than other allied occupational groups that also practice ergonomics, however they indicated that there may be difficulties in the “real world” applying these areas of knowledge into practice. Participants who demonstrated a high level of awareness of the relation between ergonomics and psychosocial hazard control demonstrated stronger organizational commitment than participants with a low awareness. Ergonomics practitioners who reported having employer support for professional development also demonstrated a higher degree of awareness of the relation between ergonomics and psychosocial hazard control, as did the professionals who had been practicing in the field the longest. This research provides some insight for professional associations for Ergonomists, employers of Ergonomists, and human resource professionals about how ergonomics practitioners perceive the ergonomics field and the profession as well as their employing organization.

Hydrothermal activity along the slow-spreading Lucky Strike ridge segment (Mid-Atlantic Ridge): Distribution, heatflux, and geological controls

We have reviewed available visual information from the seafloor, and recently acquired microbathymetry for several traverses across the Lucky Strike segment, to evaluate the distribution of hydrothermal activity. We have identified a new on-axis site with diffuse flow, Ewan, and an active vent structure ∼1.2 km from the axis, Capelinhos. These sites are minor relative to the Main field, and our total heatflux estimate for all active sites (200–1200 MW) is only slightly higher than previously published estimates. We also identify fossil sites W of the main Lucky Strike field. A circular feature ∼200 m in diameter located on the flanks of a rifted off-axis central volcano is likely a large and inactive hydrothermal edifice, named Grunnus. We find no indicator of focused hydrothermal activity elsewhere along the segment, suggesting that the enhanced melt supply and the associated melt lenses, required to form central volcanoes, also sustain hydrothermal circulation to form and maintain large and long-lived hydrothermal fields. Hydrothermal discharge to the seafloor occurs along fault traces, suggesting focusing of hydrothermal circulation in the shallow crust along permeable fault zones.

Sea-level control on the connection between shelf-edge deltas and the Bourcart canyon head (western Mediterranean) during the last glacial/interglacial cycle

A dense grid of high- and very high resolution seismic data, together with piston cores and borehole data providing time constraints, enables us to reconstruct the history of the Bourcart canyon head in the western Mediterranean Sea during the last glacial/interglacial cycle. The canyon fill is composed of confined channel–levee systems fed by a series of successively active shelf fluvial systems, originating from the west and north. Most of the preserved infill corresponds to the interval between Marine Isotope Stage (MIS) 3 and the early deglacial (19 cal ka BP). Its deposition was strongly controlled by a relative sea level that impacted the direct fluvial/canyon connection. During a period of around 100 kyr between MIS 6 and MIS 2, the canyon “prograded” by about 3 km. More precisely, several parasequences can be identified within the canyon fill. They correspond to forced-regressed parasequences (linked to punctuated sea-level falls) topped by a progradational-aggradational parasequence (linked to a hypothetical 19-ka meltwater pulse (MWP)). The bounding surfaces between forced-regressed parasequences are condensed intervals formed during intervals of relative sediment starvation due to flooding episodes. The meandering pattern of the axial incision visible within the canyon head, which can be traced landward up to the Agly paleo-river, is interpreted as the result of hyperpycnal flows initiated in the river mouth in a context of increased rainfall and mountain glacier flushing during the early deglacial.

Low temperature magneto-photoluminescence characterization of high purity gallium arsenide and indium phosphide

Low-temperature magneto-photoluminescence is a very powerful technique to characterize high purity GaAs and InP grown by various epitaxial techniques. These III-V compound semiconductor materials are used in a wide variety of electronic, optoelectronic and microwave devices. The large binding energy differences of acceptors in GaAs and InP make possible the identification of those impurities by low-temperature photoluminescence without the use of any magnetic field. However, the sensitivity and resolution provided by this technique rema1ns inadequate to resolve the minute binding energy differences of donors in GaAs and InP. To achieve higher sensitivity and resolution needed for the identification of donors, a magneto-photoluminescence system 1s installed along with a tunable dye laser, which provides resonant excitation. Donors 1n high purity GaAs are identified from the magnetic splittings of "two-electron" satellites of donor bound exciton transitions 1n a high magnetic field and at liquid helium temperature. This technique 1s successfully used to identify donors 1n n-type GaAs as well as 1n p-type GaAs in which donors cannot be identified by any other technique. The technique is also employed to identify donors in high purity InP. The amphoteric incorporation of Si and Ge impurities as donors and acceptors in (100), (311)A and (3ll)B GaAs grown by molecular beam epitaxy is studied spectroscopically. The hydrogen passivation of C acceptors in high purity GaAs grown by molecular beam epitaxy (MBE) and metalorganic chemical vapor deposition (MOCVD) 1s investigated using photoluminescence. Si acceptors ~n MBE GaAs are also found to be passivated by hydrogenation. The instabilities in the passivation of acceptor impurities are observed for the exposure of those samples to light. Very high purity MOCVD InP samples with extremely high mobility are characterized by both electrical and optical techniques. It is determined that C is not typically incorporated as a residual acceptor ~n high purity MOCVD InP. Finally, GaAs on Si, single quantum well, and multiple quantum well heterostructures, which are fabricated from III-V semiconductors, are also measured by low-temperature photoluminescence.

Recommended reporting standards for test accuracy studies of infectious diseases of finfish, amphibians, molluscs and crustaceans: the STRADAS-aquatic checklist

Complete and transparent reporting of key elements of diagnostic accuracy studies for infectious diseases in cultured and wild aquatic animals benefits end-users of these tests, enabling the rational design of surveillance programs, the assessment of test results from clinical cases and comparisons of diagnostic test performance. Based on deficiencies in the Standards for Reporting of Diagnostic Accuracy (STARD) guidelines identified in a prior finfish study (Gardner et al. 2014), we adapted the Standards for Reporting of Animal Diagnostic Accuracy Studies—paratuberculosis (STRADAS-paraTB) checklist of 25 reporting items to increase their relevance to finfish, amphibians, molluscs, and crustaceans and provided examples and explanations for each item. The checklist, known as STRADAS-aquatic, was developed and refined by an expert group of 14 transdisciplinary scientists with experience in test evaluation studies using field and experimental samples, in operation of reference laboratories for aquatic animal pathogens, and in development of international aquatic animal health policy. The main changes to the STRADAS-paraTB checklist were to nomenclature related to the species, the addition of guidelines for experimental challenge studies, and the designation of some items as relevant only to experimental studies and ante-mortem tests. We believe that adoption of these guidelines will improve reporting of primary studies of test accuracy for aquatic animal diseases and facilitate assessment of their fitness-for-purpose. Given the importance of diagnostic tests to underpin the Sanitary and Phytosanitary agreement of the World Trade Organization, the principles outlined in this paper should be applied to other World Organisation for Animal Health (OIE)-relevant species.

Results of a feasibility study: barriers and facilitators in implementing the Sherbrooke model in France.

International audience

Using landscape metrics to predict hydrologic connectivity patterns between forested wetlands and streams in a coastal plain watershed

Geographically isolated wetlands, those entirely surrounded by uplands, provide numerous ecological functions, some of which are dependent on the degree to which they are hydrologically connected to nearby waters. There is a growing need for field-validated, landscape-scale approaches for classifying wetlands based on their expected degree of connectivity with stream networks. During the 2015 water year, flow duration was recorded in non-perennial streams (n = 23) connecting forested wetlands and nearby perennial streams on the Delmarva Peninsula (Maryland, USA). Field and GIS-derived landscape metrics (indicators of catchment, wetland, non-perennial stream, and soil characteristics) were assessed as predictors of wetland-stream connectivity (duration, seasonal onset and offset dates). Connection duration was most strongly correlated with non-perennial stream geomorphology and wetland characteristics. A final GIS-based stepwise regression model (adj-R2 = 0.74, p < 0.0001) described wetland-stream connection duration as a function of catchment area, wetland area and number, and soil available water storage.

ENZYME-FREE UBIQUITIN LIGATION. FROM NATIVE CHEMICAL LIGATION AND SPIN LABELING TO DIMERIZATION BY INTER-UBIQUITIN MIMICKING LINKAGE AND PH-DEPENDENT CONFORMATIONAL SWITCH

The delicate balance between the production and disposal of proteins is vital for the changes required in the cell to respond to given stimulus. Ubiquitination is a protein modification with a range of signaling outcomes when ubiquitin is attached to a protein through a highly ordered enzymatic cascade process. Understanding ubiquitination is a growing field and nowadays the application of chemical reactions allows the isolation of quantitative materials for structural studies. Therefore, in this dissertation it is described some of these suitable chemical methodologies to produce an isopeptide bond toward the polymerization of ubiquitin bypassing the enzymatic control with the purpose of showing if these chemical modifications have a direct impact on the structure of ubiquitin. First, the possibility of incorporating non-natural lysine analogs known as mercaptolysines into the polypeptide chain of Ubiquitin was explored when they were attached to ubiquitin by native chemical ligation at its C terminus. The sulfhydryl group was used for the attachment of a paramagnetic label to map the surface of ubiquitin. Second, the condensation catalyzed by silver nitrate was used for the dimer assembly. In particular, the main focus was on examining whether orthogonal protection and deprotection of each monomer have an impact on the reaction yield, since the synthetic strategy has been previously attempted successfully. Third, the formation of ubiquitin dimers was approached by building an inter-ubiquitin linkage mimicking the isopeptide bond with two approaches, the classic disulfide exchange as well as the thiol-ene click reaction by thermal initiation in aqueous conditions. After assembling the dimeric units, they were studied by Nuclear Magnetic Resonance, in order to establish a conformational state profile which depends on the pH conditions. The latter is a very important concept since some ligands have a preferred affinity when the protein-protein hydrophobic patches are in close proximity.