Objectives/Goals: Large-scale tumor sequencing efforts have led to annotations of novel cancer hotspot mutations that may underlie driver or cooperative function. We have sought to define the molecular consequences of such hotspots associated with pediatric DICER1 syndrome cancers, with the ultimate goal of revealing novel targets that may inform new standards of care. Methods/Study Population: We have performed genomic analysis to identify tumor types (in TCGA and MSK-IMPACT patient data) for which mutations in the Dicer1 gene (encoding Dicer protein) emerge as the dominant signature of driver function. As Dicer is a critical RNA processing factor responsible for the generation of microRNAs, which are posttranscriptional gene regulatory molecules, we have modeled these mutations in human embryonic stem cells in order to study the direct effects on miRNAs and their target genes in an isogenic background. In addition to providing the required setting for unambiguous attribution of function to specific mutations, clonal human ES cells offer an opportunity for modeling of both developmental and cancer requirements associated with altered Dicer function. Results/Anticipated Results: Through generation of genomics and functional datasets from matched genotypes in Dicer mutated human ES cells, we have identified specific alterations in miRNAs and their effects on target genes. Unexpectedly, we found direct evidence for both loss of function and gain of function attributable to Dicer mutations. In addition, through integrated analysis of genomic data from tumor sequencing datasets and our human ES cell models, we have identified potential miRNA and target gene alterations that underlie tumorigenic potential, nominating gene candidates for targeted therapy in DICER1 syndrome. Direct mouse modeling of such candidate gene targets has revealed evidence for driver function of identified miRNA and their targets. Discussion/Significance of Impact: DICER1 syndrome cancers comprise a wide variety of rare pediatric tumor types. Presently, we still lack an effective standard of care. Furthermore, the previous lack of molecular profiling precluded targeted therapy opportunities. Our precise knock-in modeling of Dicer hotspots and deep profiling of relevant tumors now provide candidate targets.

When and why did House parties identify exclusive committees? The nexus of parties and standing committees defines the distribution of power in the U.S. House of Representatives, shapes legislators’ careers, and affects Congress's ability to address the nation's problems. Yet, political science provides inadequate and often misleading characterizations of the parties and the most important standing committees. We provide missing detail and offer a historical perspective on party efforts to arrange standing committees in the period since the revolt against Speaker Joseph Cannon in 1909–1910. Our narrative offers a foundation for explaining party efforts to regulate committee membership and meet legislators’ demands. For the first time, we define three periods in committee assignment limitations. In doing so, we place key events in historical context: We report that the modern exclusive committees (Appropriations, Rules, and Ways and Means) did not become defined until the 1950s; the identification by the two parties of a larger set of exclusive committees for which a one-assignment limitation applied began decades earlier; the Legislative Reorganization Act of 1946 placed a one-assignment limitation in House rules that had been party practice for three decades by then. In recent decades, deep partisanship has been accompanied by a loosening, not tightening, of restrictions. In fact, there are no fully exclusive committees remaining in practice.

The Galactic Center contains large amounts of molecular and ionized gas as well as a plethora of energetic objects. Water masers are an extinction-insensitive probe for star formation and thus ideal for studies of star formation stages in this highly obscured region. With the Australia Telescope Compact Array, we observed 22 GHz water masers in the entire Central Molecular Zone with sub-parsec resolution as part of the large SWAG survey: “Survey of Water and Ammonia in the Galactic Center”. We detect of order 600 22 GHz masers with isotropic luminosities down to ~10−7 L⊙. Masers with luminosities of ≳10−6 L⊙ are likely associated with young stellar objects. They appear to be close to molecular gas streamers and may be due to star formation events that are triggered at pericenter passages near Sgr A*. Weaker masers are more widely distributed and frequently show double line features, a tell-tale sign for an origin in evolved star envelopes.

SWAG (“Survey of Water and Ammonia in the Galactic Center”) is a multi-line interferometric survey toward the Center of the Milky Way conducted with the Australia Telescope Compact Array. The survey region spans the entire ~400 pc Central Molecular Zone and comprises ~42 spectral lines at pc spatial and sub-km/s spectral resolution. In addition, we deeply map continuum intensity, spectral index, and polarization at the frequencies where synchrotron, free-free, and thermal dust sources emit. The observed spectral lines include many transitions of ammonia, which we use to construct maps of molecular gas temperature, opacity and gas formation temperature (see poster by Nico Krieger et al., this volume). Water masers pinpoint the sites of active star formation and other lines are good tracers for density, radiation field, shocks, and ionization. This extremely rich survey forms a perfect basis to construct maps of the physical parameters of the gas in this extreme environment.

On 23 May 2011, CDC identified a multistate cluster of Salmonella Heidelberg infections and two multidrug-resistant (MDR) isolates from ground turkey retail samples with indistinguishable pulsed-field gel electrophoresis patterns. We defined cases as isolation of outbreak strains in persons with illness onset between 27 February 2011 and 10 November 2011. Investigators collected hypothesis-generating questionnaires and shopper-card information. Food samples from homes and retail outlets were collected and cultured. We identified 136 cases of S. Heidelberg infection in 34 states. Shopper-card information, leftover ground turkey from a patient's home containing the outbreak strain and identical antimicrobial resistance profiles of clinical and retail samples pointed to plant A as the source. On 3 August, plant A recalled 36 million pounds of ground turkey. This outbreak increased consumer interest in MDR Salmonella infections acquired through United States-produced poultry and played a vital role in strengthening food safety policies related to Salmonella and raw ground poultry.

We analyze a high resolution (114″ × 60″) 74 MHz image of the Galactic center taken with the Very Large Array (VLA). We have identified several absorption and emission features in this region, and we discuss preliminary results of two Galactic center sources: the Sgr D complex (G1.1–0.1) and the Galactic center lobe (GCL).

The 74 MHz image displays the thermal and nonthermal components of Sgr D and we argue the Sgr D supernova remnant (SNR) is consistent with an interaction with a nearby molecular cloud and the location of the Sgr D Hii region on the near side of the Galactic center. The image also suggests that the emission from the eastern side of the GCL contains a mixture of both thermal and nonthermal sources, whereas the western side is primarily thermal.

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behavior. It is not clear, however, if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children of siblings and children of twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant monozygotic twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene–environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association.

Five Euphorbiaceae species (Jatropha macrocarpa, J. hieronymi, J. excisa, Cnidoscolus tubulosus and Manihot guaranitica) were analysed for seed oil content and fatty acid profiles in order to evaluate their potential as sources of biodiesel. The five species are perennial shrubs adapted to arid and semi-arid environments of north-western Argentina. The seed oil content for all species ranged from 27.9 to 38.7% by dry weight. Fatty acid composition consisted mainly of linolenic, myristic, palmitic, stearic, arachidic, oleic and linoleic acids, with linoleic and oleic acid being the most abundant. Among the five species analysed, J. macrocarpa has the best potential to be used as a biodiesel source. The average total seed oil content (35.8%) and a high value of oleic acid (27.3%) together with the lowest values of linoleic acid (55.8%) make this species a promising crop as a source of biodiesel in arid and semi-arid regions.

Frequency-dependent opacities are determined for high-Z plasma taking into account splitting of the energy levels with orbital quantum number l. The energy levels are calculated with the help of the screened hydrogenic model generalized by Perrot for l splitting. Oscillator strengths for bound-bound and bound-free transitions are computed from hydrogenic wave functions with two different screened nuclear charges. The average atom model is used to determine the plasma state, with provision for continuum lowering and pressure ionization. Explicit results for extinction coefficients of gold plasma with ρ = 0.1 g/cm3 and T = 100−500 eV are compared with calculations neglecting l splitting. Considerably enhanced absorption at lower photon energies (50–300 eV) is obtained when taking l splitting into account. Planck and Rosseland mean opacities are also calculated and compared with data contained in the SESAME opacity library. Remarkable agreement is found without any artificial line broadening or band smearing.

The Si'lailo Way: Indians, Salmon and Law on the Columbia River. Joseph C. Dupris, Kathleen S. Hill, and William H. Rodgers, Jr. 2006. Carolina Academic Press, Durham, NC. 450 pp. $40 paperback.

It is impossible to work in the environmental field in the Pacific Northwest without knowing something of salmon: their epic journeys from river to sea and back; the legendary runs of the nineteenth century, before the arrival of dynamite, fish wheels, dams, and hatcheries; the near-symbiotic relationship between the Northwest Indian tribes and the fish that were the backbone of their diet and culture. Those who pay any attention at all to the area's history are aware that serious injustice was done to the native people and fish of the Columbia River. The Si'lailo Way makes that injustice tangible by adding lavishly illustrated characters and a narrative that viscerally connects the reader to the people and places that fell victim to what the authors depict as a 150-year campaign to rid the Columbia of its native human and piscine inhabitants.

Earthly Politics: Local and Global in Environmental Governance. Sheila Jasanoff and Marybeth Long Martello, eds. 2004. The MIT Press, Cambridge, MA. 376 pp. $27 paperback.

Environmental governance today usually involves negotiations—often lengthy and complex—between scientists, policy makers, and other stakeholders such as business leaders and citizens' groups. Although full inclusion and democratic participation in such negotiations is a lofty goal held by many involved, the decisions about who should be included as a stakeholder, and what influence their experience and perspective should be given in comparison to that of scientists, are ultimately political. These decisions are the subjects of Earthly Politics and, as the editors strive to show, they are highly placed-based and variable.

An Unnatural Metropolis: Wresting New Orleans from Nature. Craig E. Colten. 2005. Louisiana State University Press, Baton Rouge, LA. 245 pp. $39.95 hardcover.

The history and geography of New Orleans, perhaps more than any other American city, is inextricably entwined with the challenges presented by the city's natural setting. In his unexpectedly timely book, An Unnatural Metropolis, author Craig E. Colten recounts this intricate relationship and the human attempt to, in effect, hold nature at bay at the mouth of the Mississippi. Although Colten covers a wide range of the dilemmas faced by New Orleans' residents over the past 300 years (many of which, such as sanitation and water delivery, were by no means unique to New Orleans among nineteenth-century cities), in light of recent events, most readers probably will be most interested in his account of New Orleans' levee and drainage systems, and the shaping of the city's modern-day racial and social geography.

In a study of the evolution of conjugated linoleic acid (CLA) during cheese production, the influence of Emmental cheese processing on the CLA content and the CLA isomer composition was evaluated. The use of raw and thermised milk, changes of processing temperature and the effect of propionic acid bacteria (PAB) were investigated. The content of CLA in raw milk was 8·6±1·9 mg/g fat and in the ripened cheese at 70 d was 8·6±1·6 mg/g fat, under normal processing conditions. No changes in the CLA content and CLA isomer composition were observed during Emmental cheese manufacturing process. Changes in cooking and moulding temperatures did not influence the CLA content. CLA content of cheese made from microfiltered milk with two different Propionibacterium freudenreichii strains was very close to cheeses made without PAB. CLA levels seem to be stable in this type of dairy product under the conditions examined.

In The Skeptical Environmentalist, Danish statistician Bjorn Lomborg delivers one overarching message: don't worry. The world is doing fine. Water, forests, fossil fuel supplies, biodiversity, and air quality are all in good shape, and most are getting better. Global human welfare is improving in every possible way. Thing are not perfect, but technology will deliver the answers to all our worries. Contemporary environmental concerns are a “litany” developed by a handful of people to serve their own agendas. Above all, Lomborg seeks to free the world from the tyranny of that litany.

Synchrotron radiation-based x-ray photoemission spectroscopy was used to study the Fermi level position within the band gap for thin metal overlayers of Au, Ni, and Ti on n-GaN and p-GaN. The Fermi level position was determined with the measured Fermi edge of the metal on the sample in order to correct for the presence of non-equilibrium effects. There are two different behaviors observed for the three metals studied. For Au and Ti, the surface Fermi positions on n-GaN and p-GaN are roughly 0.5 eV apart within the band gap. For Ni, the n-GaN and p-GaN have a Schottky barrier that forms at the same place at the gap.