Pathway Semantics: An Algebraic Data Driven Algorithm to Generate Hypotheses about Molecular Patterns Underlying Disease Progression

The overarching goal of the Pathway Semantics Algorithm (PSA) is to improve the in silico identification of clinically useful hypotheses about molecular patterns in disease progression. By framing biomedical questions within a variety of matrix representations, PSA has the flexibility to analyze combined quantitative and qualitative data over a wide range of stratifications. The resulting hypothetical answers can then move to in vitro and in vivo verification, research assay optimization, clinical validation, and commercialization. Herein PSA is shown to generate novel hypotheses about the significant biological pathways in two disease domains: shock / trauma and hemophilia A, and validated experimentally in the latter. The PSA matrix algebra approach identified differential molecular patterns in biological networks over time and outcome that would not be easily found through direct assays, literature or database searches. In this dissertation, Chapter 1 provides a broad overview of the background and motivation for the study, followed by Chapter 2 with a literature review of relevant computational methods. Chapters 3 and 4 describe PSA for node and edge analysis respectively, and apply the method to disease progression in shock / trauma. Chapter 5 demonstrates the application of PSA to hemophilia A and the validation with experimental results. The work is summarized in Chapter 6, followed by extensive references and an Appendix with additional material.

Dietary patterns and body mass index of Canadian Inuit communities in 1999 and 2008

Objectives: The International Polar Year (IPY) Inuit Health Survey provided an opportunity to compare dietary and body mass index (BMI) data with data collected a decade earlier for the same communities. Study design: A dietary survey included 1,929 randomly selected participants aged 15 years or older, selected from 18 Inuit communities in 1998-1999. The IPY survey included 2,595 randomly selected participants aged 18 years or older, selected from 36 Inuit communities in 2007-2008. Data from the same 18 communities included in both surveys were compared for adults 20 years and older. Methods: Twenty-four-hour dietary recall data were analysed to assess the percentage of energy from traditional and market foods by sex and age groups. Body mass index (BMI) was assessed to establish the prevalence of obesity by sex and age groups in both surveys. Results: There was a significant decrease (p<=0.05) in energy contribution from traditional food and a significant increase in market food consumption over time. Sugar-sweetened beverages, chips and pasta all increased as percentages of energy. BMI increased overall for women and for each age stratum evaluated (p<0.05). Conclusion: The nutrition transition continues in the Canadian Arctic with a concurrent increase in BMI.

Constraints on the magnitude and patterns of ocean cooling at the Last Glacial Maximum - Supplementary material

Observation-based reconstructions of sea surface temperature from relatively stable periods in the past, such as the Last Glacial Maximum, represent an important means of constraining climate sensitivity and evaluating model simulations. The first quantitative global reconstruction of sea surface temperatures during the Last Glacial Maximum was developed by the Climate Long-Range Investigation, Mapping and Prediction (CLIMAP) project in the 1970s and 1980s. Since that time, several shortcomings of that earlier effort have become apparent. Here we present an updated synthesis of sea surface temperatures during the Last Glacial Maximum, rigorously defined as the period between 23 and 19 thousand years before present, from the Multiproxy Approach for the Reconstruction of the Glacial Ocean Surface (MARGO) project. We integrate microfossil and geochemical reconstructions of surface temperatures and include assessments of the reliability of individual records. Our reconstruction reveals the presence of large longitudinal gradients in sea surface temperature in all of the ocean basins, in contrast to the simulations of the Last Glacial Maximum climate available at present.

Surface sediment analyses, bivalve and gastropod taxa of marine sediments from the Banc d'Arguin, Mauritania

High-nutrient tropical carbonate systems are known to produce sediments that, in terms of skeletal composition, are reminiscent of their extra-tropical counterparts. Such carbonate systems and associated carbonate grain assemblages in the tropics are rare in the present-day world. Nonetheless, it is crucial to gain a better understanding of those ecosystems, including their drivers and players because such settings potentially represent models for ancient depositional systems as well as for predicted future environmental conditions. One of the modern occurrences of eutrophic tropical carbonate systems is the northern Mauritanian Shelf. The marine environment is characterized by an eastern boundary upwelling system that pushes cool and nutrient-rich intermediate waters onto a wide epicontinental platform (Golfe d'Arguin) where the waters warm up to tropical temperatures. The resulting facies is mixed carbonate-siliciclastic with a dominant foramol association grading into bimol and barnamol grain assemblages in the shallowest areas forming the Banc d'Arguin. Besides this cool water-related heterozoan association, the carbonate sediment is characterized by tropical molluskan species, while chlorozoan biota (e.g., corals and algal symbiont-bearing foraminifers) are entirely absent. We here present a first comprehensive facies analysis of this model example of eutrophic tropical carbonates. Furthermore, we reconstruct the loci of carbonate production and provide a conclusive depositional model of the Banc d'Arguin that received little attention to date due to its poorly accessible nature.

Secchi disk data collection for the North Sea and Baltic Sea

This paper presents the results of a Secchi depth data mining study for the North Sea - Baltic Sea region. 40,829 measurements of Secchi depth were compiled from the area as a result of this study. 4.3% of the observations were found in the international data centers [ICES Oceanographic Data Center in Denmark and the World Ocean Data Center A (WDC-A) in the USA], while 95.7% of the data was provided by individuals and ocean research institutions from the surrounding North Sea and Baltic Sea countries. Inquiries made at the World Ocean Data Center B (WDC-B) in Russia suggested that there could be significant additional holdings in that archive but, unfortunately, no data could be made available. The earliest Secchi depth measurement retrieved in this study dates back to 1902 for the Baltic Sea, while the bulk of the measurements were gathered after 1970. The spatial distribution of Secchi depth measurements in the North Sea is very uneven with surprisingly large sampling gaps in the Western North Sea. Quarterly and annual Secchi depth maps with a 0.5° x 0.5° spatial resolution are provided for the transition area between the North Sea and the Baltic Sea (4°E-16°E, 53°N-60°N).

Seasonal production patterns of planktonic foraminifera in the NE Atlantic Ocean

Sediment trap samples from OMEX 2 (49°N, 13°W) provide a continuous record of the seasonal succession of planktonic foraminifera in the midlatitude North Atlantic and reveal a complex relationship between periods of production and specific hydrographic conditions. Neogloboquadrina pachyderma dextral coiling (d.), Globigerina bulloides, and Globorotalia inflata are found in great numbers during both the spring and summer seasons, whereas Globigerina quinqueloba, Globorotalia hirsuta, Globorotalia scitula, and Globigerinita glutinata are associated predominantly with the increase in productivity during the spring bloom. Globigerinella aequilateralis, Orbulina universa, and Globigerinoides sacculifer are restricted to late summer conditions following the establishment of a warm, well-stratified surface ocean. An annually integrated fauna from the sediment trap, comprising ~13,000 individuals, is used to evaluate the accuracy of five faunal-based statistical methods of paleotemperature estimation. All of the temperature reconstruction techniques produce estimates of ~16°C and ~11°C for summer and winter surface temperature, respectively, which are in excellent agreement with regional hydrographic data and suggest that the sediment trap assemblage is well represented in the core top faunas. Analysis of the key species that dominate the OMEX 2 sediment trap fauna, G. bulloides, G. inflata, and N. pachyderma d., based on d18O derived temperatures from North Atlantic core top samples, suggests that seasonal variations in planktonic foraminiferal production are nonuniform across the midlatitudes and that this is likely to complicate reconstructing past seasonal hydrographic dynamics using these taxa.

Amount and patterns of beluga sightings in the eastern Beaufort Sea

An understanding of the adaptability of belugas (Delphinapterus leucas) to changing ice conditions is required to interpret and predict possible changes in habitat selection in response to projected loss of sea ice throughout the circumpolar Arctic. We analyzed beluga observations made during spring aerial surveys for ringed seals conducted from 1975 to 1979 in the eastern Beaufort Sea. Despite interannual variability in the extent and distribution of sea ice, belugas consistently selected areas with water depths of 200-500 m and heavy ice concentrations (8/10 to 10/10) while areas of open water to light ice concentrations (0/10 to 1/10) were not selected. Belugas were also found in proximity to regions with >0.5 degrees seafloor slope which include the continental slope and other areas with the potential for oceanographic upwellings. In most years (4 of 5), fast-ice edges and coastal areas were not selected. In the lightest ice year analyzed, belugas showed less specificity in habitat selection as their distribution expanded and shifted shoreward to fast-ice edges. The observed distribution is discussed in terms of predator-prey relationships particularly with reference to beluga feeding on polar cod (Boreogadus saida). More research is required to examine and compare possible changes in distribution since the late 1970s and to investigate the factors driving the patterns described.

Multiproxy sedimentation patterns of sediment cores from the continental margin off northeast Brazil

Tropical regions have been reported to play a key role in climate dynamics. To date, however, there are uncertainties in the timing and the amplitude of the response of tropical ecosystems to millennial-scale climate change. We present evidence of an asynchrony between terrestrial and marine signals of climate change during Heinrich events preserved in marine sediment cores from the Brazilian continental margin. The inferred time lag of about 1000 to 2000 years is much larger than the ecological response to recent climate change and appears to be related to the nature of hydrological changes.

The Global Plankton Database: an inventory and data from the Former Soviet Union expeditions

At present time, there is a lack of knowledge on the interannual climate-related variability of zooplankton communities of the tropical Atlantic, central Mediterranean Sea, Caspian Sea, and Aral Sea, due to the absence of appropriate databases. In the mid latitudes, the North Atlantic Oscillation (NAO) is the dominant mode of atmospheric fluctuations over eastern North America, the northern Atlantic Ocean and Europe. Therefore, one of the issues that need to be addressed through data synthesis is the evaluation of interannual patterns in species abundance and species diversity over these regions in regard to the NAO. The database has been used to investigate the ecological role of the NAO in interannual variations of mesozooplankton abundance and biomass along the zonal array of the NAO influence. Basic approach to the proposed research involved: (1) development of co-operation between experts and data holders in Ukraine, Russia, Kazakhstan, Azerbaijan, UK, and USA to rescue and compile the oceanographic data sets and release them on CD-ROM, (2) organization and compilation of a database based on FSU cruises to the above regions, (3) analysis of the basin-scale interannual variability of the zooplankton species abundance, biomass, and species diversity.