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Sökning: WFRF:(Golub M.)

  • Resultat 1-10 av 28
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1.
  • Sabatini, F. M., et al. (författare)
  • sPlotOpen - An environmentally balanced, open-access, global dataset of vegetation plots
  • 2021
  • Ingår i: Global Ecology and Biogeography. - 1466-822X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Motivation Assessing biodiversity status and trends in plant communities is critical for understanding, quantifying and predicting the effects of global change on ecosystems. Vegetation plots record the occurrence or abundance of all plant species co-occurring within delimited local areas. This allows species absences to be inferred, information seldom provided by existing global plant datasets. Although many vegetation plots have been recorded, most are not available to the global research community. A recent initiative, called 'sPlot', compiled the first global vegetation plot database, and continues to grow and curate it. The sPlot database, however, is extremely unbalanced spatially and environmentally, and is not open-access. Here, we address both these issues by (a) resampling the vegetation plots using several environmental variables as sampling strata and (b) securing permission from data holders of 105 local-to-regional datasets to openly release data. We thus present sPlotOpen, the largest open-access dataset of vegetation plots ever released. sPlotOpen can be used to explore global diversity at the plant community level, as ground truth data in remote sensing applications, or as a baseline for biodiversity monitoring. Main types of variable contained Vegetation plots (n = 95,104) recording cover or abundance of naturally co-occurring vascular plant species within delimited areas. sPlotOpen contains three partially overlapping resampled datasets (c. 50,000 plots each), to be used as replicates in global analyses. Besides geographical location, date, plot size, biome, elevation, slope, aspect, vegetation type, naturalness, coverage of various vegetation layers, and source dataset, plot-level data also include community-weighted means and variances of 18 plant functional traits from the TRY Plant Trait Database. Spatial location and grain Global, 0.01-40,000 m(2). Time period and grain 1888-2015, recording dates. Major taxa and level of measurement 42,677 vascular plant taxa, plot-level records. Software format Three main matrices (.csv), relationally linked.
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2.
  • Penney, K. L., et al. (författare)
  • mRNA expression signature of Gleason grade predicts lethal prostate cancer
  • 2011
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:17, s. 2391-2396
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis.PATIENTS AND METHODS: Using the complementary DNA-mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases.RESULTS: We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006).CONCLUSION: Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.
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3.
  • Vanderkelen, I., et al. (författare)
  • Global Heat Uptake by Inland Waters
  • 2020
  • Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 47:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Heat uptake is a key variable for understanding the Earth system response to greenhouse gas forcing. Despite the importance of this heat budget, heat uptake by inland waters has so far not been quantified. Here we use a unique combination of global‐scale lake models, global hydrological models and Earth system models to quantify global heat uptake by natural lakes, reservoirs, and rivers. The total net heat uptake by inland waters amounts to 2.6 ± 3.2 ×1020 J over the period 1900–2020, corresponding to 3.6% of the energy stored on land. The overall uptake is dominated by natural lakes (111.7%), followed by reservoir warming (2.3%). Rivers contribute negatively (‐14%) due to a decreasing water volume. The thermal energy of water stored in artificial reservoirs exceeds inland water heat uptake by a factor ∼10.4. This first quantification underlines that the heat uptake by inland waters is relatively small, but non‐negligible.
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4.
  • Ferraro, Gino B., et al. (författare)
  • Fatty acid synthesis is required for breast cancer brain metastasis
  • 2021
  • Ingår i: Nature Cancer. - 2662-1347. ; 2:4, s. 414-428
  • Tidskriftsartikel (refereegranskat)abstract
    • Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2-positive breast cancer and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, resulting in site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase reduces human epidermal growth factor receptor 2-positive breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.
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6.
  • Setlur, Sunita R., et al. (författare)
  • Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer
  • 2008
  • Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford univ. press. - 0027-8874 .- 1460-2105. ; 100:11, s. 815-825
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The majority of prostate cancers harbor gene fusions of the 5'-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. METHODS: We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians(') Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. RESULTS: We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81; P < .001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ERbeta agonist (ERbeta agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at day 8, mean = 4.36 vs 3.40, difference = 0.96, 95% CI = 0.68 to 1.23). Similarly, expression of TMPRSS2-ERG decreased after ERbeta agonist treatment (fold change over internal control, ERbeta agonist vs vehicle at 24 hours, NCI-H660, mean = 0.57- vs 1.0-fold, difference = 0.43-fold, 95% CI = 0.29- to 0.57-fold) and increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at 24 hours, mean = 5.63- vs 1.0-fold, difference = 4.63-fold, 95% CI = 4.34- to 4.92-fold). CONCLUSIONS: TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel ER-dependent mechanism.
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8.
  • Gustafson, Deborah, 1966, et al. (författare)
  • Anthropometric measures and cognition in middle-aged HIV-infected and uninfected women. The Women's Interagency HIV Study
  • 2013
  • Ingår i: Journal of Neurovirology. - 1355-0284. ; 19:6, s. 574-585
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to explore the relationship of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with cognition in women with (HIV+) and without HIV (HIV-) infection. One thousand six hundred ninety participants (1,196 HIV+, 494 HIV-) in the Women's Interagency HIV Study (WIHS) with data available on anthropometric measures comprise the analytical sample. Cross-sectional analyses using linear regression models estimated the relationship between anthropometric variables and Trails A, Trails B, Stroop interference time, Stroop word recall, Stroop color naming and reading, and Symbol Digit Modalities Test (SDMT) with consideration for age, HIV infection status, Wide Range Achievement Test score, CD4 count, insulin resistance, drug use, and race/ethnicity. Among HIV+ women, BMI<18.5 kg/m(2) was associated with poorer cognitive performance evidenced by longer Trails A and Trails B and shorter SDMT completion times. An obese BMI (30 kg/m(2) or higher) was related to better performance on Trails B and worse performance on the Stroop interference test. Among HIV-women, an obese BMI was related to worse performance on the Stroop color naming test. Few and inconsistent associations were observed between WC, WHR, and cognition. Among women at mid-life with chronic (at least 10 years) HIV infection, common anthropometric measures, primarily BMI, were differentially related to cognitive test performance by cognitive domain. Higher levels of BMI were associated with better cognitive function. In this era of antiretroviral therapies, restoration of health evidenced as higher BMI due to effective antiretroviral therapies, may improve cognitive function in middle-aged HIV-infected women.
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10.
  • Murphy, K., et al. (författare)
  • Association of self-reported race with AIDS death in continuous HAART users in a cohort of HIV-infected women in the United States
  • 2013
  • Ingår i: Aids. - 0269-9370. ; 27:15, s. 2413-2423
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective:To assess the association of race with clinical outcomes in HIV-positive women on continuous HAART.Design:Prospective study that enrolled women from 1994 to 1995 and 2001 to 2002.Setting:Women's Interagency HIV Study, a community-based cohort in five US cities.Participants:One thousand, four hundred and seventy-one HIV-positive continuous HAART users.Main outcome measures:Times to AIDS and non-AIDS death and incident AIDS-defining illness (ADI) after HAART initiation.Results:In adjusted analyses, black vs. white women had higher rates of AIDS death [adjusted hazard ratio (aHR) 2.14, 95% confidence interval (CI) 1.30, 3.50; P=0.003] and incident ADI (aHR 1.58, 95% CI 1.08, 2.32; P=0.02), but not non-AIDS death (aHR 0.91, 95% CI 0.59, 1.39; P=0.65). Cumulative AIDS death incidence at 10 years was 17.3 and 8.3% for black and white women, respectively. Other significant independent pre-HAART predictors of AIDS death included peak viral load (aHR 1.70 per log(10), 95% CI 1.34, 2.16; P<0.001), nadir CD4(+) cell count (aHR 0.65 per 100cells/l, 95% CI 0.56, 0.76; P<0.001), depressive symptoms by Center for Epidemiology Studies Depression score at least 16 (aHR 2.10, 95% CI 1.51, 2.92; P<0.001), hepatitis C virus infection (aHR 1.57, 95% CI 1.02, 2.40; P=0.04), and HIV acquisition via transfusion (aHR 2.33, 95% CI 1.21, 4.49; P=0.01). In models with time-updated HAART adherence, association of race with AIDS death remained statistically significant (aHR 3.09, 95% CI 1.38, 6.93; P=0.006).Conclusion:In continuous HAART-using women, black women more rapidly died from AIDS or experienced incident ADI than their white counterparts after adjusting for confounders. Future studies examining behavioral and biologic factors in these women may further the understanding of HAART prognosis.
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