The future of climate modeling

Recently a number of scientists have proposed substantial changes to the practice of climate modeling, though they disagree over what those changes should be. We provide an overview and critical examination of three leading proposals: the unified approach, the hierarchy approach and the pluralist approach. The unified approach calls for an accelerated development of high-resolution models within a seamless prediction framework. The hierarchy approach calls for more attention to the development and systematic study of hierarchies of related models, with the aim of advancing understanding. The pluralist approach calls for greater diversity in modeling efforts, including, on some of its variants, more attention to empirical modeling. After identifying some of the scientific and institutional challenges faced by these proposals, we consider their expected gains and costs, relative to a business-as-usual modeling scenario.We find the proposals to be complementary, having valuable synergies. But since resource limitations make it unlikely that all three will be pursued, we offer some reflections on more limited changes in climate modeling that seem well within reach and that can be expected to yield substantial benefits

Ultraviolet and Optical Observations of OB Associations and Field Stars in the Southwest Region of the Large Magellanic Cloud

Using photometry from the Ultraviolet Imaging Telescope (UIT) and photometry and spectroscopy from three ground-based optical datasets we have analyzed the stellar content of OB associations and field areas in and around the regions N 79, N 81, N 83, and N 94 in the LMC. We compare data for the OB association Lucke-Hodge 2 (LH 2) to determine how strongly the initial mass function (IMF) may depend on different photometric reductions and calibrations. We also correct for the background contribution of field stars, showing the importance of correcting for field star contamination in determinations of the IMF of star formation regions. It is possible that even in the case of an universal IMF, the variability of the density of background stars could be the dominant factor creating the differences between calculated IMFs for OB associations. We have also combined the UIT data with the Magellanic Cloud Photometric Survey to study the distribution of the candidate O-type stars in the field. We find a significant fraction, roughly half, of the candidate O-type stars are found in field regions, far from any obvious OB associations. These stars are greater than 2 arcmin (30 pc) from the boundaries of existing OB associations in the region, which is a distance greater than most O-type stars with typical dispersion velocities will travel in their lifetimes. The origin of these massive field stars (either as runaways, members of low-density star-forming regions, or examples of isolated massive star formation) will have to be determined by further observations and analysis.Comment: 16 pages, 10 figures (19 PostScript files), tabular data + header file for Table 1 (2 ASCII files). File format is LaTeX/AASTeX v.502 using the emulateapj5 preprint style (included). Also available at http://www.boulder.swri.edu/~joel/papers.html . To appear in the February 2001 issue of the Astronomical Journa

Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>The goal of this study was to understand gene expression signatures of hepatocellular carcinoma (HCC) recurrence in subjects with hepatitis C virus (HCV) infection. Recurrence-free survival (RFS) following curative resection of HCC in subjects with HCV is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized patient management. Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS.</p> <p>Results</p> <p>The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGFβ1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses.</p> <p>Conclusions</p> <p>Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression predictor may hold important insights into the pathobiology of HCC recurrence and <it>de novo </it>tumor formation in cirrhotic patients.</p

The Nature and Frequency of the Gas Outbursts in Comet 67P/Churyumov-Gerasimenko observed by the Alice Far-ultraviolet Spectrograph on Rosetta

Alice is a far-ultraviolet imaging spectrograph onboard Rosetta that, amongst multiple objectives, is designed to observe emissions from various atomic and molecular species from within the coma of comet 67P/Churyumov-Gerasimenko. The initial observations, made following orbit insertion in August 2014, showed emissions of atomic hydrogen and oxygen spatially localized close to the nucleus and attributed to photoelectron impact dissociation of H2O vapor. Weaker emissions from atomic carbon were subsequently detected and also attributed to electron impact dissociation, of CO2, the relative H I and C I line intensities reflecting the variation of CO2 to H2O column abundance along the line-of-sight through the coma. Beginning in mid-April 2015, Alice sporadically observed a number of outbursts above the sunward limb characterized by sudden increases in the atomic emissions, particularly the semi-forbidden O I 1356 multiplet, over a period of 10-30 minutes, without a corresponding enhancement in long wavelength solar reflected light characteristic of dust production. A large increase in the brightness ratio O I 1356/O I 1304 suggests O2 as the principal source of the additional gas. These outbursts do not correlate with any of the visible images of outbursts taken with either OSIRIS or the navigation camera. Beginning in June 2015 the nature of the Alice spectrum changed considerably with CO Fourth Positive band emission observed continuously, varying with pointing but otherwise fairly constant in time. However, CO does not appear to be a major driver of any of the observed outbursts.Comment: 6 pages, 4 figures, accepted for publication in the Astrophysical Journal Letter

Potential Tumor Suppressor Role for the c-Myb Oncogene in Luminal Breast Cancer

The transcription factor c-Myb has been well characterized as an oncogene in several human tumor types, and its expression in the hematopoietic stem/progenitor cell population is essential for proper hematopoiesis. However, the role of c-Myb in mammopoeisis and breast tumorigenesis is poorly understood, despite its high expression in the majority of breast cancer cases (60-80%).We find that c-Myb high expression in human breast tumors correlates with the luminal/ER+ phenotype and a good prognosis. Stable RNAi knock-down of endogenous c-Myb in the MCF7 luminal breast tumor cell line increased tumorigenesis both in vitro and in vivo, suggesting a possible tumor suppressor role in luminal breast cancer. We created a mammary-derived c-Myb expression signature, comprised of both direct and indirect c-Myb target genes, and found it to be highly correlated with a published mature luminal mammary cell signature and least correlated with a mammary stem/progenitor lineage gene signature.These data describe, for the first time, a possible tumor suppressor role for the c-Myb proto-oncogene in breast cancer that has implications for the understanding of luminal tumorigenesis and for guiding treatment

Optimization of neural network architecture using genetic programming improves detection and modeling of gene-gene interactions in studies of human diseases

BACKGROUND: Appropriate definition of neural network architecture prior to data analysis is crucial for successful data mining. This can be challenging when the underlying model of the data is unknown. The goal of this study was to determine whether optimizing neural network architecture using genetic programming as a machine learning strategy would improve the ability of neural networks to model and detect nonlinear interactions among genes in studies of common human diseases. RESULTS: Using simulated data, we show that a genetic programming optimized neural network approach is able to model gene-gene interactions as well as a traditional back propagation neural network. Furthermore, the genetic programming optimized neural network is better than the traditional back propagation neural network approach in terms of predictive ability and power to detect gene-gene interactions when non-functional polymorphisms are present. CONCLUSION: This study suggests that a machine learning strategy for optimizing neural network architecture may be preferable to traditional trial-and-error approaches for the identification and characterization of gene-gene interactions in common, complex human diseases

Cells exhibiting strong p16INK4a promoter activation in vivo display features of senescence

The activation of cellular senescence throughout the lifespan promotes tumor suppression, whereas the persistence of senescent cells contributes to aspects of aging. This theory has been limited, however, by an inability to identify and isolate individual senescent cells within an intact organism. Toward that end, we generated a murine reporter strain by “knocking-in” a fluorochrome, tandem-dimer Tomato (tdTom), into exon 1α of the p16 INK4a locus. We used this allele (p16 tdTom ) for the enumeration, isolation, and characterization of individual p16 INK4a -expressing cells (tdTom + ). The half-life of the knocked-in transcript was shorter than that of the endogenous p16 INK4a mRNA, and therefore reporter expression better correlated with p16 INK4a promoter activation than p16 INK4a transcript abundance. The frequency of tdTom + cells increased with serial passage in cultured murine embryo fibroblasts from p16 tdTom/+ mice. In adult mice, tdTom + cells could be readily detected at low frequency in many tissues, and the frequency of these cells increased with aging. Using an in vivo model of peritoneal inflammation, we compared the phenotype of cells with or without activation of p16 INK4a and found that tdTom + macrophages exhibited some features of senescence, including reduced proliferation, senescence-associated β-galactosidase (SA-β-gal) activation, and increased mRNA expression of a subset of transcripts encoding factors involved in SA-secretory phenotype (SASP). These results indicate that cells harboring activation of the p16 INK4a promoter accumulate with aging and inflammation in vivo, and display characteristics of senescence