47 research outputs found

    Stardust-NExT, Deep Impact, and the Accelerating Spin of 9P/Tempel One

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    The evolution of the spin rate of comet 9P/Tempel 1 through two perihelion passages (CYs 2000 and 2005) is determined from 1922 Earth-based observations taken over a period of 13y as part of a World-Wide observing campaign and 2888 observations taken over a period of 50d from the Deep Impact spacecraft. We determine the following sidereal spin rates (periods): 209.023 +/- 0.025 degrees /day (41.335 +/- 0.005 h) prior to the 2000 perihelion passage, 210.448 +/- 0.016 degrees/day (41.055 +/- 0.003 h) for the interval between the 2000 and 2005 perihelion passages, 211.856 +/- 0.030 degrees/day (40.783 +/- 0.006 h) from Deep Impact photometry just prior to the 2005 perihelion passage, and 211.625 +/- 0.012 degrees /day (40.827 +/- 0.002 h) in the interval 2006-2010 following the 2005 perihelion passage. The period decreased by 16.8 +/- 0.3 min during the 2000 passage and by 13.7 +/- 0.2 min during the 2005 passage suggesting a secular decrease in the net torque. The change in spin rate is asymmetric with respect to perihelion with the maximum net torque being applied on approach to perihelion. The Deep Impact data alone show that the spin rate was increasing at a rate of 0.024 +/- 0.003 degree/d/d at JD2453530.60510 (i.e., 25.134 d before impact) and provides independent confirmation of the change seen in the Earth-based observations. The rotational phase of the nucleus at times before and after each perihelion and at the Deep Impact encounter is estimated based on the Thomas et al. pole and longitude system. The possibility of a 180 degree error in the rotational phase is assessed and found to be significant. Analytical and physical modeling of the behavior of the spin rate through of each perihelion is presented and used as a basis to predict the rotational state of the nucleus at the time of the nominal (i.e., prior to February 2010) Stardust-NExT encounter on 2011 February 14 20:42. We find that a net torque in the range of 0.3 - 2.5 x 10(exp 7) kg.square m2/square s acts on the nucleus during perihelion passage. The spin rate initially slows down on approach to perihelion and then passes through a minimum. It then accelerates rapidly as it passes through perihelion eventually reaching a maximum post-perihelion. It then decreases to a stable value as the nucleus moves away from the sun. We find that the pole direction is unlikely to precess by more than approximately 1 degree/perihelion passage. The trend of the period with time and the fact that the modeled peak torque that occurs before perihelion is in agreement with published accounts of trends in water production rate and suggests that widespread H2O out-gassing from the surface is largely responsible for the observed spin-up

    Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21

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    Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e−8) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e−11). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer pre-disposition locus

    Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG

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    BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite‐based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome‐wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13–25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC , an important gene in PC biology. CONCLUSIONS These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer. Prostate 72:410–426, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90245/1/21443_ftp.pd

    Resource Utilization and Cost-Effectiveness of Counselor- vs. Provider-Based Rapid Point-of-Care HIV Screening in the Emergency Department

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    Routine HIV screening in emergency department (ED) settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor.We employed a mathematical model to extend data obtained from a randomized clinical trial of provider- vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1) no screening program; 2) an ED provider-based program; and 3) an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%). Undiagnosed HIV prevalence (0.4%) and linkage to care rates (80%) were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs.Estimated HIV screening costs in the provider and counselor arms averaged 8.10and8.10 and 31.00 per result received. The Provider strategy (compared to no screening) had an incremental cost-effectiveness ratio of 58,700/qualityadjustedlifeyear(QALY)andtheCounselorstrategy(comparedtotheProviderstrategy)hadanincrementalcosteffectivenessratioof58,700/quality-adjusted life year (QALY) and the Counselor strategy (compared to the Provider strategy) had an incremental cost-effectiveness ratio of 64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs.The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in situations where ED staff resources may be insufficient to provide comprehensive, sustainable screening services

    The calcareous brown alga Padina pavonica in southern Britain: population change and tenacity over 300 years

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    Understanding long-term persistence and variability in species populations can help to predict future survival, growth and distribution; however, sustained observations are exceedingly rare. We examine and interpret a remarkable record of the calcareous brown alga Padina pavonica (Phaeophyceae) at its northern limit on the south coast of England (50°N, 1–3°W) from 1680 to 2014, which is probably the longest compilation and review of any marine algal species. Over this period, which extends from the middle of the Little Ice Age to the present, there has been considerable variability in temperature and storminess. We identified a significant number of site extinctions in the second half of the nineteenth century, which coincided with cooler conditions and stormier weather. To interpret thesechanges, we measured recruitment, growth and production of tetraspores at sheltered and exposed sites in 2012–2014, years which had low and high spring temperatures. Potential spore production was greater at the sheltered site due to a longer growing period and survival of larger fronds. Delayed growth in the cooler spring resulted in smaller fronds and lower potential production of tetraspores by early summer. Yet in the warmer year, rapid initial growth caused higher sensitivity to damage and dislodgement by summer storms, which also limited potential spore production. Antagonistic responses to multiple stressors and disturbances make future predictions of survival and distribution difficult. Fronds of Padina pavonica are sensitive to both temperature and physical disturbances, yet vegetative perennation appears to have enabled population persistence and explained the longevity of remaining populations

    Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.

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    BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Loregic: A Method to Characterize the Cooperative Logic of Regulatory Factors

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    The topology of the gene-regulatory network has been extensively analyzed. Now, given the large amount of available functional genomic data, it is possible to go beyond this and systematically study regulatory circuits in terms of logic elements. To this end, we present Loregic, a computational method integrating gene expression and regulatory network data, to characterize the cooperativity of regulatory factors. Loregic uses all 16 possible twoinput- one-output logic gates (e.g. AND or XOR) to describe triplets of two factors regulating a common target. We attempt to find the gate that best matches each triplet’s observed gene expression pattern across many conditions. We make Loregic available as a generalpurpose tool (github.com/gersteinlab/loregic). We validate it with known yeast transcriptionfactor knockout experiments. Next, using human ENCODE ChIP-Seq and TCGA RNA-Seq data, we are able to demonstrate how Loregic characterizes complex circuits involving both proximally and distally regulating transcription factors (TFs) and also miRNAs. Furthermore, we show that MYC, a well-known oncogenic driving TF, can be modeled as acting independently from other TFs (e.g., using OR gates) but antagonistically with repressing miRNAs. Finally, we inter-relate Loregic’s gate logic with other aspects of regulation, such as indirect binding via protein-protein interactions, feed-forward loop motifs and global regulatory hierarchy
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