C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells.

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance

Livestock grazing and vegetative filter strip buffer effects on runoff sediment, nitrate, and phosphorus losses

Livestock grazing in the Midwestern United States can result in significant levels of runoff sediment and nutrient losses to surface water resources. Some of these contaminants can increase stream eutrophication and are suspected of contributing to hypoxic conditions in the Gulf of Mexico. This research quantified effects of livestock grazing management practices and vegetative filter strip buffers on runoff depth and mass losses of total solids, nitrate-nitrogen (NO3-N), and ortho-phosphorus (PO4-P) under natural hydrologic conditions. Runoff data were collected from 12 rainfall events during 2001 to 2003 at an Iowa State University research farm in central Iowa, United States. Three vegetative buffers (paddock area:vegetative buffer area ratios of 1:0.2, 1:0.1, and 1:0 no buffer [control]) and three grazing management practices (continuous, rotational, and no grazing [control]) comprised nine treatment combinations (vegetative buffer ratio/grazing management practice) replicated in three 1.35 ha (3.34 ac) plot areas. The total 4.05 ha (10.02 ac) study area also included nine 0.4 ha (1.0 ac) paddocks and 27 vegetative buffer runoff collection units distributed in a randomized complete block design. The study site was established on uneven terrain with a maximum of 15% slopes and consisted of approximately 100% cool-season smooth bromegrass. Average paddock and vegetative buffer plant tiller densities estimated during the 2003 project season were approximately 62 million and 93 million tillers ha−1 (153 million and 230 million tillers ac−1), respectively. Runoff sample collection pipe leakage discovered and corrected during 2001 possibly reduced runoff depth and affected runoff contaminant mass losses data values. Consequently, 2001 runoff analysis results were limited to treatment comparisons within the 2001 season and were not compared with 2002 and 2003 data. Analysis results from 2001 showed no significant differences in average losses of runoff, total solids, NO3-N, and PO4-P among the nine vegetative buffer/grazing practice treatment combinations. Results from 2002 indicated significantly higher losses of runoff and total solids from 1:0 no buffer/rotational grazing and 1:0 no buffer/continuous grazing treatment combination plots, respectively, compared among other 2002 season treatment combinations. The 2003 results showed significantly higher runoff and total solids losses from 1:0 no buffer/no grazing treatment combination plots compared among all 2003 treatment combinations and from 1:0.1 vegetative buffer/no grazing treatment combination plots compared among all 2003 treatment combinations and with respective 2002 treatment combinations. However, the 2003 results indicated effective vegetative buffer performance with significantly lower runoff, total solids, and NO3-N losses from the larger 1:0.2 buffer area compared among the smaller 1:0.1 buffer area and 1:0 no buffer treatment combinations. The 2003 results also indicated a highly significant increase in losses of NO3-N from 1:0.1 buffer/no grazing treatment combination plots compared among other 2003 season treatment combinations and with respective 2002 treatment combinations. Overall results from this study suggest a shift from significantly higher 2002 season plot losses of continuous and rotational grazing treatment combinations to significantly higher 2003 season losses of no grazing treatment combinations. We speculate this shift to significantly higher runoff and contaminant losses from no grazing treatment combination plots during 2003 reflects the variability inherent to a complex and dynamic soil-water environment of livestock grazing areas. However, we also hypothesize the environmental conditions that largely consisted of a dense perennial cool-season grass type, high-relief landscape, and relatively high total rainfall depth may not necessarily include livestock grazing activities

Tests of a large air‐core superconducting solenoid as a nuclear‐reaction‐product spectrometer

An air‐core superconducting solenoid, with a diameter of 0.2 m and a length of 0.4 m, has been configured for use as a heavy‐ion reaction‐product spectrometer (E/A≤5 MeV/u) near θ=0° (10 to 35 msr). The performance of the spectrometer was established using α‐particle sources and nuclear‐reaction products from (18O, 18Ne), (18O, 20Ne) and (18O, 14O) and masses determined for 30Mg, 108Ru and 109Rh. A system suitable for production of radioactive beams has been constructed, and in‐beam tests are in progress at the University of Notre Dame. Large air‐core solenoids with dΩ≤20 msr and capable of focusing ions with E/A≥30 MeV/u appear feasible.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87304/2/845_1.pd

Role of Rare-Earth Oxide Additives on Mechanical Properties and Oxidation Behavior of Si 3 N 4 /BN Fibrous Monolith Ceramics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65415/1/j.1551-2916.2006.00911.x.pd

Elastic scattering and breakup of 17^F at 10 MeV/nucleon

Angular distributions of fluorine and oxygen produced from 170 MeV 17^F incident on 208^Pb were measured. The elastic scattering data are in good agreement with optical model calculations using a double-folding potential and parameters similar to those obtained from 16^O+208^Pb. A large yield of oxygen was observed near \theta_lab=36 deg. It is reproduced fairly well by a calculation of the (17^F,16^O) breakup, which is dominated by one-proton stripping reactions. The discrepancy between our previous coincidence measurement and theoretical predictions was resolved by including core absorption in the present calculation.Comment: 9 pages, 5 figure

Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium

Background<p></p> Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk.<p></p> Methods and Results<p></p> We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026).<p></p> Conclusion<p></p> Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings

Magnetized Particle Capture Cross Section for Braneworld Black Hole

Capture cross section of magnetized particle (with nonzero magnetic moment) by braneworld black hole in uniform magnetic field is considered. The magnetic moment of particle was chosen as it was done by \citet{rs99} and for the simplicity particle with zero electric charge is chosen. It is shown that the spin of particle as well as the brane parameter are to sustain the stability of particles circularly orbiting around the black hole in braneworld i.e. spin of particles and brane parameter try to prevent the capture by black hole.Comment: 7 pages, 4 figures, Accepted for publication in Astrophysics & Space Scienc

Crystal Structure of the Formin mDia1 in Autoinhibited Conformation

Formin proteins utilize a conserved formin homology 2 (FH2) domain to nucleate new actin filaments. In mammalian diaphanous-related formins (DRFs) the FH2 domain is inhibited through an unknown mechanism by intramolecular binding of the diaphanous autoinhibitory domain (DAD) and the diaphanous inhibitory domain (DID).Here we report the crystal structure of a complex between DID and FH2-DAD fragments of the mammalian DRF, mDia1 (mammalian diaphanous 1 also called Drf1 or p140mDia). The structure shows a tetrameric configuration (4 FH2 + 4 DID) in which the actin-binding sites on the FH2 domain are sterically occluded. However biochemical data suggest the full-length mDia1 is a dimer in solution (2 FH2 + 2 DID). Based on the crystal structure, we have generated possible dimer models and found that architectures of all of these models are incompatible with binding to actin filament but not to actin monomer. Furthermore, we show that the minimal functional monomeric unit in the FH2 domain, termed the bridge element, can be inhibited by isolated monomeric DID. NMR data on the bridge-DID system revealed that at least one of the two actin-binding sites on the bridge element is accessible to actin monomer in the inhibited state.Our findings suggest that autoinhibition in the native DRF dimer involves steric hindrance with the actin filament. Although the structure of a full-length DRF would be required for clarification of the presented models, our work here provides the first structural insights into the mechanism of the DRF autoinhibition

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson