The evolutionary dynamics of genomic regulatory blocks in metazoan genomes

Developmental genes require intricate control of the timing, location and magnitude of their expression. This is provided by multiple evolutionarily conserved enhancers, known as conserved non-coding elements (CNEs). CNEs cluster around their target genes, forming long syntenic arrays known as genomic regulatory blocks (GRBs). Current methods for GRB identification rely on the selection of arbitrary minimum conservation thresholds, impeding their performance in many contexts. In this thesis, I propose a novel measure of pairwise genome conservation that eliminates the need for conservation thresholds, and use this measure to study the evolutionary dynamics of GRBs in metazoa. I define sets of GRBs based on their rate of regulatory turnover – high turnover GRBs (htGRBs) and low turnover GRBs (ltGRBs) – in three independent metazoan lineages. I show that ht- and ltGRBs target functionally distinct classes of genes, and that these genes tend to be expressed during late and early development respectively, potentially contributing to their differing tolerance of regulatory turnover. Moreover, the differences between ht- and ltGRBs are consistent across all three lineages, suggesting that similar evolutionary pressures have defined the rate of turnover in these GRBs since their emergence in the metazoan ancestor. Next I identify GRBs in the extremely compact Caenorhabditis elegans and Oikopleura dioica genomes for the first time, and use these GRBs to investigate the effects of genome compaction on GRB size and composition. I show that GRB size scales proportionally with genome size and that GRBs exhibit similar enrichment and depletion of specific genomic features. This suggests that regardless of background genome content, GRBs are under similar pressure to maintain a permissive environment for long-range gene regulation. The development of a threshold-free GRB identification method has facilitated the analysis of GRBs in both closely related species and compact genomes, providing further insights into their origin and evolution.Open Acces

Incremental Phi*: Incremental Any-Angle Path Planning on Grids

We study path planning on grids with blocked and unblocked cells. Any-angle path-planning algorithms find short paths fast because they propagate information along grid edges without constraining the resulting paths to grid edges. Incremental path-planning algorithms solve a series of similar path-planning problems faster than repeated single-shot searches because they reuse information from the previous search to speed up the next one. In this paper, we combine these ideas by making the any-angle path-planning algorithm Basic Theta* incremental. This is non-trivial because Basic Theta* does not fit the standard assumption that the parent of a vertex in the search tree must also be its neighbor. We present Incremental Phi* and show experimentally that it can speed up Basic Theta* by about one order of magnitude for path planning with the freespace assumption

Size reconstructibility of graphs

The deck of a graph $G$ is given by the multiset of (unlabelled) subgraphs $\{G-v:v\in V(G)\}$. The subgraphs $G-v$ are referred to as the cards of $G$. Brown and Fenner recently showed that, for $n\geq29$, the number of edges of a graph $G$ can be computed from any deck missing 2 cards. We show that, for sufficiently large $n$, the number of edges can be computed from any deck missing at most $\frac1{20}\sqrt{n}$ cards.Comment: 15 page

Esmeralda Energy Company Final Scientific Technical Report, January 2008, Emigrant Slimhole Drilling Project, DOE GRED III (DE-FC36-04GO14339)

The Emigrant Slimhole Drilling Project (“ESDP”) was a highly successful, phased resource evaluation program designed to evaluate the commercial geothermal potential of the eastern margin of the northern Fish Lake Valley pull-apart basin in west-central Nevada. The program involved three phases: (1) Resource evaluation; (2) Drilling and resource characterization; and (3) Resource testing and assessment. Efforts included detailed geologic mapping; 3-D modeling; compilation of a GIS database; and production of a conceptual geologic model followed by the successful drilling of the 2,938 foot deep 17-31 slimhole (core hole), which encountered commercial geothermal temperatures (327⁰ F) and exhibits an increasing, conductive, temperature gradient to total depth; completion of a short injection test; and compilation of a detailed geologic core log and revised geologic cross-sections. Results of the project greatly increased the understanding of the geologic model controlling the Emigrant geothermal resource. Information gained from the 17-31 core hole revealed the existence of commercial temperatures beneath the area in the Silver Peak Core Complex which is composed of formations that exhibit excellent reservoir characteristics. Knowledge gained from the ESDP may lead to the development of a new commercial geothermal field in Nevada. Completion of the 17-31 core hole also demonstrated the cost-effectiveness of deep core drilling as an exploration tool and the unequaled value of core in understanding the geology, mineralogy, evolutional history and structural aspects of a geothermal resource

Genetic response to human-induced habitat changes in the marine environment: A century of evolution of European sprat in Landvikvannet, Norway

Habitat changes represent one of the five most pervasive threats to biodiversity. However, anthropogenic activities also have the capacity to create novel niche spaces to which species respond differently. In 1880, one such habitat alterations occurred in Landvikvannet, a freshwater lake on the Norwegian coast of Skagerrak, which became brackish after being artificially connected to the sea. This lake is now home to the European sprat, a pelagic marine fish that managed to develop a self-recruiting population in barely few decades. Landvikvannet sprat proved to be genetically isolated from the three main populations described for this species; that is, Norwegian fjords, Baltic Sea, and the combination of North Sea, Kattegat, and Skagerrak. This distinctness was depicted by an accuracy self-assignment of 89% and a highly significant FST between the lake sprat and each of the remaining samples (average of ≈0.105). The correlation between genetic and environmental variation indicated that salinity could be an important environmental driver of selection (3.3% of the 91 SNPs showed strong associations). Likewise, Isolation by Environment was detected for salinity, although not for temperature, in samples not adhering to an Isolation by Distance pattern. Neighbor-joining tree analysis suggested that the source of the lake sprat is in the Norwegian fjords, rather than in the Baltic Sea despite a similar salinity profile. Strongly drifted allele frequencies and lower genetic diversity in Landvikvannet compared with the Norwegian fjords concur with a founder effect potentially associated with local adaptation to low salinity. Genetic differentiation (FST) between marine and brackish sprat is larger in the comparison Norway-Landvikvannet than in Norway-Baltic, which suggests that the observed divergence was achieved in Landvikvannet in some 65 generations, that is, 132 years, rather than gradually over thousands of years (the age of the Baltic Sea), thus highlighting the pace at which human-driven evolution can happen.publishedVersio

Adaptation and conservation insights from the koala genome

The koala, the only extant species of the marsupial family Phascolarctidae, is classified as ‘vulnerable’ due to habitat loss and widespread disease. We sequenced the koala genome, producing a complete and contiguous marsupial reference genome, including centromeres. We reveal that the koala’s ability to detoxify eucalypt foliage may be due to expansions within a cytochrome P450 gene family, and its ability to smell, taste and moderate ingestion of plant secondary metabolites may be due to expansions in the vomeronasal and taste receptors. We characterized novel lactation proteins that protect young in the pouch and annotated immune genes important for response to chlamydial disease. Historical demography showed a substantial population crash coincident with the decline of Australian megafauna, while contemporary populations had biogeographic boundaries and increased inbreeding in populations affected by historic translocations. We identified genetically diverse populations that require habitat corridors and instituting of translocation programs to aid the koala’s survival in the wild

ISOPAR L RELEASE RATES FROM SALTSTONE USING SIMULATED SALT SOLUTIONS

The Modular Caustic-Side Solvent Extraction (CSSX) Unit (MCU) and the Salt Waste Processing Facility (SWPF) will produce a Decontaminated Salt Solution (DSS) that will go to the Saltstone Production Facility (SPF). Recent information indicates that solvent entrainment in the DSS is larger than expected. The main concern is with Isopar{reg_sign} L, the diluent in the solvent mixture, and its flammability in the saltstone vault. If it is assumed that all the Isopar{reg_sign} L is released instantaneously into the vault from the curing grout before each subsequent pour, the Isopar{reg_sign} L in the vault headspace is well mixed, and each pour displaces an equivalent volume of headspace, the maximum concentration of Isopar{reg_sign} L in the DSS to assure 25% of the lower flammable limit is not exceeded has been determined to be about 4 ppm. The amount allowed would be higher if the release from grout were significantly less. The Savannah River National Laboratory was tasked with determining the release of Isopar{reg_sign} L from saltstone prepared with a simulated DSS with Isopar{reg_sign} L concentrations ranging from 50 to 200 mg/L in the salt fraction and with test temperatures ranging from ambient to 95 C. The results from the curing of the saltstone showed that the amount of Isopar{reg_sign} L released versus time can be treated as a percentage of initial amount present; there was no statistically significant dependence of the release rate on the initial concentration. The majority of the Isopar{reg_sign} L that was released over the test duration was released in the first few days. The release of Isopar{reg_sign} L begins immediately and the rate of release decreases over time. At higher temperatures the immediate release rate is larger than at lower temperatures. Initial curing temperature was found to be very important as slight variations during the first few hours or days had a significant effect on the amount of Isopar{reg_sign} L released. Short scoping tests at 95 C with solvent containing all components (Isopar{reg_sign} L, suppressor trioctylamine (TOA), and modifier Cs-7SB) except the BOBCalixC6 extractant released less Isopar{reg_sign} L than the tests run with Isopar{reg_sign} L/TOA. Based on these scoping tests, the Isopar{reg_sign} L releases reported herein are conservative. Isopar{reg_sign} L release was studied for a two-month period and average cumulative release rates were determined from three sets of tests each at 95 and 75 C and at ambient conditions. The overall average releases at were estimated for each temperature. For the 95 and 75 C data, at a 5% significance level, the hypothesis that the three test sets at each temperature had the same average percent release can be rejected, suggesting that there was a statistically significant difference among the three averages seen in the three experimental tests conducted. An upper confidence limit on the mean percent release required incorporation of variation from two sources: test-to-test variation as well as the variation within a test. An analysis of variance that relies on a random effects model was used to estimate the two variance components. The test-to-test variance and the within test (or residual) variance were both calculated. There is no indication of a statistically significant linear correlation between the percent Isopar{reg_sign} L release and the Isopar{reg_sign} L initial concentration. From the analysis of variance, upper confidence limits at confidences of 80-95% were calculated for the data at 95 and 75 C. The mean Isopar{reg_sign} L percent releases were 67.33% and 13.17% at 95 and 75 C, respectively

Radioactive Demonstration Of Mineralized Waste Forms Made From Hanford Low Activity Waste (Tank SX-105 And AN-103) By Fluidized Bed Steam Reformation

One of the immobilization technologies under consideration as a Supplemental Treatment for Hanford’s Low Activity Waste (LAW) is Fluidized Bed Steam Reforming (FBSR). The FBSR technology forms a mineral waste form at moderate processing temperatures thus retaining and atomically bonding the halides, sulfates, and technetium in the mineral phases (nepheline, sodalite, nosean, carnegieite). Additions of kaolin clay are used instead of glass formers and the minerals formed by the FBSR technology offers (1) atomic bonding of the radionuclides and constituents of concern (COC) comparable to glass, (2) short and long term durability comparable to glass, (3) disposal volumes comparable to glass, and (4) higher Na2O and SO{sub 4} waste loadings than glass. The higher FBSR Na{sub 2}O and SO{sub 4} waste loadings contribute to the low disposal volumes but also provide for more rapid processing of the LAW. Recent FBSR processing and testing of Hanford radioactive LAW (Tank SX-105 and AN-103) waste is reported and compared to previous radioactive and non-radioactive LAW processing and testing

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al