Killing the Straw Man: Does BICEP Prove Inflation at the GUT Scale?

The surprisingly large value of $r$, the ratio of power in tensor to scalar density perturbations in the CMB reported by the BICEP2 Collaboration, if confirmed, provides strong evidence for Inflation at the GUT scale. While the Inflationary signal remains the best motivated source, a large value of $r$ alone would still allow for the possibility that a comparable gravitational wave background might result from a self ordering scalar field (SOSF) transition that takes place later at somewhat lower energy. We find that even without detailed considerations of the predicted BICEP signature of such a transition, simple existing limits on the isocurvature contribution to CMB anisotropies would definitively rule out a contribution of more than $5\%$ to $r \approx 0.2$,. We also present a general relation for the allowed fractional SOSF contribution to $r$ as a function of the ultimate measured value of $r$. These results point strongly not only to an inflationary origin of the BICEP2 signal, if confirmed, but also to the fact that if the GUT scale is of order $10^{16} GeV$ then either the GUT transition happens before Inflation or the Inflationary transition and the GUT transition must be one and the same.Comment: 3 pages 2 figures, accepted for publication in Physics Letters B . Accepted version revised slightly in response to referee's comment

VALUING LOSSES FROM DEPOPULATING MICHIGAN DAIRY HERDS

Depopulating dairy herds in the effort to eradicate disease would have significant economic effects. This paper evaluates farm-level effects that might occur and puts forth a method for quantifying losses. The reader is directed elsewhere for industry or state-level effects of disease eradication or depopulation.Livestock Production/Industries,

An RNA Interference Lethality Screen of the Human Druggable Genome to Identify Molecular Vulnerabilities in Epithelial Ovarian Cancer

Targeted therapies have been used to combat many tumor types; however, few have effectively improved the overall survival in women with epithelial ovarian cancer, begging for a better understanding of this deadly disease and identification of essential drivers of tumorigenesis that can be targeted effectively. Therefore, we used a loss-of-function screening approach to help identify molecular vulnerabilities that may represent key points of therapeutic intervention. We employed an unbiased high-throughput lethality screen using a 24,088 siRNA library targeting over 6,000 druggable genes and studied their effects on growth and/or survival of epithelial ovarian cancer (EOC) cell lines. The top 300 “hits” affecting the viability of A1847 cells were rescreened across additional EOC cell lines and non-tumorigenic, human immortalized ovarian epithelial cell lines. Fifty-three gene candidates were found to exhibit effects in all tumorigenic cell lines tested. Extensive validation of these hits refined the list to four high quality candidates (HSPA5, NDC80, NUF2, and PTN). Mechanistic studies show that silencing of three genes leads to increased apoptosis, while HSPA5 silencing appears to alter cell growth through G1 cell cycle arrest. Furthermore, two independent gene expression studies show that NDC80, NUF2 and PTN were significantly aberrantly overexpressed in serous adenocarcinomas. Overall, our functional genomics results integrated with the genomics data provide an important unbiased avenue towards the identification of prospective therapeutic targets for drug discovery, which is an urgent and unmet clinical need for ovarian cancer

Colloid-Facilitated Transport of Radionuclides Through The Vadose Zone

The main purpose of this project was to advance the basic scientific understanding of colloid and colloid-facilitated Cs transport of radionuclides in the vadose zone. We focused our research on the hydrological and geochemical conditions beneath the leadking waste tanks at the USDOE Hanford reservation. Specific objectives were (1) to determine the lability and thermodynamic stability of colloidal materials, which form after reacting Hanford sediments with simulated Hanford Tank Waste, (2) to characterize the interactions between colloidal particles and contaminants, i.e., Cs and Eu, (3) to determine the potential of Hanford sediments for in situe mobilization of colloids, (4) to evaluate colloid-facilitated radionuclide transport through sediments under unsaturated flow, (5) to implement colloid-facilitated contaminant transport mechanisms into a transport model, and (6) to improve conceptual characterization of colloid-contaminant-soil interactions and colloid-facilitated transport for clean-up procedures and long-term risk assessment

Colloid-Facilitated Transport of Radionuclides through the Vadose Zone

This project seeks to improve the basic understanding of the role of colloids in facilitating the transport of contaminants in the vadose zone. We focus on three major thrusts: (1) thermodynamic stability and mobility of colloids formed by reactions of sediments with highly alkaline tank waste solutions, (2) colloid-contaminant interactions, and (3) in situ colloid mobilization and colloid-facilitated contaminant transport occurring in both contaminated and uncontaminated Hanford sediments

Colloid-Facilitated Transport of Radionuclides through the Vadose Zone

The main purpose of this project was to advance the basic scientific understanding of colloid and colloid-facilitated Cs transport of radionuclides in the vadose zone. We focused our research on the hydrological and geochemical conditions beneath the leaking waste tanks at the USDOE Hanford reservation. Specific objectives were (1) to determine the lability and thermodynamic stability of colloidal materials, which form after reacting Hanford sediments with simulated Hanford Tank Waste, (2) to characterize the interactions between colloidal particles and contaminants, i.e., Cs and Eu, (3) to determine the potential of Hanford sediments for \textit{in situ} mobilization of colloids, (4) to evaluate colloid-facilitated radionuclide transport through sediments under unsaturated flow, (5) to implement colloid-facilitated contaminant transport mechanisms into a transport model, and (6) to improve conceptual characterization of colloid-contaminant-soil interactions and colloid-facili\-tated transport for clean-up procedures and long-term risk assessment. We have previously shown that upon contact with simulated waste tank solutions, Hanford sediments change their mineralogical composition. Certain minerals, i.e., quartz, smectite, and kaolinite, are partially dissolved, and new mineral phases, i.e., the feldspathoids cancrinite and sodalite, are formed. We have characterized these mineral transformations and clarified the mineral transformation pathways. The new minerals were mainly in the colloidal size fraction (diameter less than 2 mum), had a negative surface charge, and were microporous, meaning they contained small pores. When Cs was present during the formation of the minerals, contaminants, like Cs, could be trapped inside the mineral structure. Transport experiments under water saturated and unsaturated conditions showed that the colloids were mobile in Hanford sediments. As the water saturation of the sediments decreased, the amount of colloids transported also decreased. The colloids had the ability to enhance the migration of the radionuclide Cs; however, Cs initially sorbed to colloids was desorbed during transport through uncontaminated Hanford sediments. The finding that Cs was stripped off the colloids during the transport through uncontaminated sediments implies that colloids will likely not be an effective carrier for Cs, unless the Cs is incorporated into the mineral structure of the colloids such that the radionuclide cannot desorb from the colloids. Nevertheless, it appears that the amount of Cs that can be transported by mobile colloids beneath Hanford waste tanks is limited. Colloids will not be able to move the bulk mass of Cs through the vadose zone at Hanford. Colloid stability studies indicate that Hanford sediment form stable colloidal suspensions when suspended in Hanford sediment pore waters. Colloid stability was assessed by determination of the critical coagulation concentration, i.e., the chemical electrolyte concentration at which colloidal suspensions flocculate and settle out (become unstable). Although in the stable mode, Hanford colloids will settle out of solution after extended periods of time (months to years). Given the low recharge rates at Hanford range, which from near 0 to more than 100 mm/year, and the long travel times for rainwater to reach the groundwater of more than 40 years, it appears that colloidal transport is unlikely to occur if colloids are initially to be suspended close to the soil surface by infiltrating rainwater. However, if preferential flow or transient flow occurs, then colloidal transport may become more important. The results of this project have also led to improvements of our fundamental understanding of colloid transport and mobilization under unsaturated flow conditions in porous media. We have found that colloid attachment to the liquid-gas interface is not that relevant and that colloids rather attached near the triple phase interface where air, water, and solid phases meet. We have also found that capillary forces are the most dominant forces governing colloid release in unsaturated porous media. These results help to advance our understanding of colloid fate and transport in unsaturated porous media

Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome. METHODS: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment. Primary endpoints were progression-free survival (PFS)≥6months and response rate. Serial plasma samples were assayed for multiple biomarkers. Circulating free DNA was quantified as were circulating tumor and endothelial cells. RESULTS: Thirty-five (35) patients were enrolled in a two-stage sequential design. Of the 34 eligible and evaluable patients, 20.6% (90% confidence interval: 10.1%, 35.2%) had a PFS≥6months; there were no objective responses. Grade 3-4 toxicities were gastrointestinal (mostly nausea and emesis; n=4), pulmonary (dyspnea and/or pleural effusion; n=4) and pain (n=5), and infrequent instances of anemia, malaise, insomnia, rash, and central nervous system hemorrhage. Lack of clinical activity limited any correlation of biomarkers with outcome. CONCLUSION: Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC

Speed breeding is a powerful tool to accelerate crop research and breeding

The growing human population and a changing environment have raised significant concern for global food security, with the current improvement rate of several important crops inadequate to meet future demand1. This slow improvement rate is attributed partly to the long generation times of crop plants. Here, we present a method called ‘speed breeding’, which greatly shortens generation time and accelerates breeding and research programmes. Speed breeding can be used to achieve up to 6 generations per year for spring wheat (Triticum aestivum), durum wheat (T. durum), barley (Hordeum vulgare), chickpea (Cicer arietinum) and pea (Pisum sativum), and 4 generations for canola (Brassica napus), instead of 2–3 under normal glasshouse conditions. We demonstrate that speed breeding in fully enclosed, controlled-environment growth chambers can accelerate plant development for research purposes, including phenotyping of adult plant traits, mutant studies and transformation. The use of supplemental lighting in a glasshouse environment allows rapid generation cycling through single seed descent (SSD) and potential for adaptation to larger-scale crop improvement programs. Cost saving through light-emitting diode (LED) supplemental lighting is also outlined. We envisage great potential for integrating speed breeding with other modern crop breeding technologies, including high-throughput genotyping, genome editing and genomic selection, accelerating the rate of crop improvement

Interaction of RNA polymerase II and the small RNA machinery affects heterochromatic silencing in Drosophila

<p>Abstract</p> <p>Background</p> <p>Heterochromatin is the tightly packaged dynamic region of the eukaryotic chromosome that plays a vital role in cellular processes such as mitosis and meiotic recombination. Recent experiments in <it>Schizosaccharomyces pombe </it>have revealed the structure of centromeric heterochromatin is affected in RNAi pathway mutants. It has also been shown in fission yeast that the heterochromatin barrier is traversed by RNA Pol II and that the passage of RNA Pol II through heterochromatin is important for heterochromatin structure. Thus, an intricate interaction between the RNAi machinery and RNA Pol II affects heterochromatin structure. However, the role of the RNAi machinery and RNA Pol II on the metazoan heterochromatin landscape is not known. This study analyses the interaction of the small RNA machinery and RNA Pol II on <it>Drosophila </it>heterochromatin structure.</p> <p>Results</p> <p>The results in this paper show genetic and biochemical interaction between RNA Pol II (largest and second largest subunit) and small RNA silencing machinery components (<it>dcr-2, ago1, ago2, piwi, Lip [D], aub </it>and <it>hls</it>). Immunofluorescence analysis of polytene chromosomes from trans-heterozygotes of RNA Pol II and different mutations of the small RNA pathways show decreased H3K9me2 and mislocalization of Heterochromatin protein-1. A genetic analysis performed on these mutants showed a strong suppression of <it>white-mottled4h </it>position effect variegation. This was further corroborated by a western blot analysis and chromatin immunoprecipitation, which showed decreased H3K9me2 in trans-heterozygote mutants compared to wild type or single heterozygotes. Co-immunoprecipitation performed using <it>Drosophila </it>embryo extracts showed the RNA Pol II largest subunit interacting with Dcr-2 and dAGO1. Co-localization performed on polytene chromosomes showed RNA Pol II and dAGO1 overlapping at some sites.</p> <p>Conclusion</p> <p>Our experiments show a genetic and biochemical interaction between RNA Pol II (largest and second largest subunits) and the small RNA silencing machinery in <it>Drosophila</it>. The interaction has functional aspects in terms of determining H3K9me2 and HP-1 deposition at the chromocentric heterochromatin. Thus, RNA Pol II has an important role in establishing heterochromatin structure in <it>Drosophila</it>.</p