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  • 1
    Electronic Resource
    Electronic Resource
    Mechanisms of Nucleic Acid Synthesis (1967)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Microbiology 21 (1967), S. 369-382 
    Details
    ISSN: 0066-4227
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.mi.21.100167.002101
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    Paper (German National Licenses)
    Fulltext
  • 2
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    Multi-scale observations of deep convection in the northwestern Mediterranean Sea during winter 2012-2013 using multiple platforms (2018)
    AGU (American Geophysical Union) | Wiley
    In:  Journal of Geophysical Research: Oceans, 123 (3). pp. 1745-1776.
    Details
    Publication Date: 2021-02-08
    Type: Article , PeerReviewed , info:eu-repo/semantics/article
    Format: text
    Format: text
    DOI: 10.1002/2016JC012671
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    OceanRep: Article in a Scientific Journal - peer-reviewed
  • 3
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    Convergence at the Caroline-Pacific plate boundary: Collision and subduction (1983)
    AGU (American Geophysical Union)
    In:  In: The Tectonic and Geologic Evolution of Southeast Asian Seas and Islands: Part 2. , ed. by Hayes, D. E. Geophysical Monograph Series, 27 . AGU (American Geophysical Union), Washington, DC, pp. 326-348, 23 pp.
    Details
    Publication Date: 2021-03-29
    Description: The eastern boundary of the Caroline plate, in the western equatorial Pacific, is composed of three structural provinces distinguished primarily on the basis of morphology. Each province shows evidence for convergence between the Caroline and Pacific plates though the structural style varies considerably between each province. Most notably, the sense of underthrusting appears to change along the boundary at about 3°N. To the south, at the Mussau System, Caroline lithosphere underthrusts beneath the Mussau Ridge (which is part of the Pacific plate), while to the north the Caroline plate appears to overthrust the Pacific plate. Recently collected seismic reflection profiles across each province documents the structural changes along and across strike of the Caroline-Pacific plate boundary. With this information, we estimate that a minimum of approximately 4 km of crustal shortening has occurred at about 5°N due to convergence of the two plates. Further to the south (about 2°N), simple gravity models suggest that about 10 km of Caroline lithosphere lies beneath the present-day Pacific plate. Using a previously determined pole of rotation describing Caroline-Pacific relative motion (Weissel and Anderson, 1978), we grossly estimate the duration of the convergence between these two plates at about one million years. It is suggested that variation in the convergence rate along the plate boundary provides the primary control on the variation of structural deformation observed between provinces; however, favorable thermal conditions are factors that are considered. If the eastern boundary of the Caroline plate is a region of incipient though perhaps transient subduction, as we postulate, then the geophysical and geological evidence presented can constrain models on the initiation of subduction.
    Type: Book chapter , PeerReviewed
    Format: text
    DOI: 10.1029/GM027p0326
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    OceanRep: Book chapter
  • 4
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    Predictors of recovery of ovarian function during aromatase inhibitor therapy (2013)
    Oxford University Press
    Details
    Publication Date: 2013-07-23
    Description: Background Aromatase inhibitors (AIs) may cause a rise in estrogen levels due to ovarian function recovery in women with clinical chemotherapy-induced ovarian failure (CIOF). We carried out a prospective registry trial to identify predictors of ovarian function recovery during AI therapy. Patients and methods Women with hormone receptor (HR)-positive breast cancer who remained amenorrheic and had hormonal levels consistent with ovarian failure after adjuvant chemotherapy were enrolled in a multi-institutional clinical trial of anastrozole. Subjects underwent frequent assessment using an ultrasensitive estradiol assay. Multivariable analysis was used to evaluate clinical and biochemical predictors of ovarian function recovery within 48 weeks. Results Recovery of ovarian function during AI therapy was observed in 13 of 45 (28.9%) assessable subjects after a median 2.1 months (range 0.6–11.9). Median age at chemotherapy initiation was statistically significantly different between those who regained ovarian function (43 years, range 40–51) and those who remained postmenopausal (49 years, range 44–52; P 〈 0.0001). Conclusions A significant proportion of women with CIOF recover ovarian function during AI therapy, including a woman over age 50 at initiation of chemotherapy. Tamoxifen remains the standard of care for women with CIOF. If an AI is used, patients should be monitored frequently with high-quality estradiol assays. Clinicaltrials.gov: NCT00555477.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
    Published by Oxford University Press
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  • 5
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    Integrated RNA and DNA sequencing improves mutation detection in low purity tumors (2014)
    Oxford University Press
    Details
    Publication Date: 2014-08-01
    Description: Identifying somatic mutations is critical for cancer genome characterization and for prioritizing patient treatment. DNA whole exome sequencing (DNA-WES) is currently the most popular technology; however, this yields low sensitivity in low purity tumors. RNA sequencing (RNA-seq) covers the expressed exome with depth proportional to expression. We hypothesized that integrating DNA-WES and RNA-seq would enable superior mutation detection versus DNA-WES alone. We developed a first-of-its-kind method, called UNCeqR , that detects somatic mutations by integrating patient-matched RNA-seq and DNA-WES. In simulation, the integrated DNA and RNA model outperformed the DNA-WES only model. Validation by patient-matched whole genome sequencing demonstrated superior performance of the integrated model over DNA-WES only models, including a published method and published mutation profiles. Genome-wide mutational analysis of breast and lung cancer cohorts ( n = 871) revealed remarkable tumor genomics properties. Low purity tumors experienced the largest gains in mutation detection by integrating RNA-seq and DNA-WES. RNA provided greater mutation signal than DNA in expressed mutations. Compared to earlier studies on this cohort, UNCeqR increased mutation rates of driver and therapeutically targeted genes (e.g. PIK3CA , ERBB2 and FGFR2 ). In summary, integrating RNA-seq with DNA-WES increases mutation detection performance, especially for low purity tumors.
    Keywords: Polymorphism/mutation detection
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    SigFuge: single gene clustering of RNA-seq reveals differential isoform usage among cancer samples (2014)
    Oxford University Press
    Details
    Publication Date: 2014-08-15
    Description: High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as biomarkers for improved prognosis and therapy. While many statistical methods have been proposed for identifying novel transcriptional events with RNA-seq, nearly all rely on contrasting known classes of samples, such as tumor and normal. Few tools exist for the unsupervised discovery of such events without class labels. In this paper, we present SigFuge for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. SigFuge combines clustering with hypothesis testing to identify genes exhibiting alternative splicing, or differences in isoform expression. We apply SigFuge to RNA-seq cohorts of 177 lung and 279 head and neck squamous cell carcinoma samples from the Cancer Genome Atlas, and identify several cases of differential isoform usage including CDKN2A , a tumor suppressor gene known to be inactivated in a majority of lung squamous cell tumors. By not restricting attention to known sample stratifications, SigFuge offers a novel approach to unsupervised screening of genetic loci across RNA-seq cohorts. SigFuge is available as an R package through Bioconductor.
    Keywords: Computational Methods
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer (2015)
    Oxford University Press
    Details
    Publication Date: 2015-12-19
    Description: Background Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC. Patients and methods Patients ( N = 297) were stratified by the number of prior therapies for metastatic disease (0–1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1 : 1 : 1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E). Each treatment arm was well balanced with regard to the proportion of patients with AR-positive breast cancer. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, clinical benefit rate, duration of response, and overall response rate. Results There was no significant difference in PFS with AA versus E (3.7 versus 3.7 months; hazard ratio [HR] = 1.1; 95% confidence interval [CI] 0.82–1.60; P = 0.437) or AAE versus E (4.5 versus 3.7 months; HR = 0.96; 95% CI 0.70–1.32; P = 0.794). Increased serum progesterone concentrations were observed in both arms receiving AA, but not with E. Grade 3 or 4 treatment-emergent adverse events associated with AA, including hypokalemia and hypertension, were less common in patients in the E (2.0% and 2.9%, respectively) and AA arms (3.4% and 1.1%, respectively) than in the AAE arm (5.8% for both). Conclusions Adding AA to E in NSAI-pretreated ER+ MBC patients did not improve PFS compared with treatment with E. An AA-induced progesterone increase may have contributed to this lack of clinical activity. ClinicalTrials.gov NCT01381874.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
    Published by Oxford University Press
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  • 8
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    Price Mean Reversion, Seasonality, and Options Markets (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-24
    Description: Options on agricultural commodities with maturities exceeding one year seldom trade. One possible reason to explain this lack of trading is that we do not have an accurate option pricing model for products where mean reversion in spot-price levels can be expected. Standard option pricing models assume proportionality between price variance and time to maturity. This proportionality is not a valid assumption for commodities whose supply response brings prices back to production costs. The model proposed here incorporates mean reversion in spot-price levels and includes a correction for seasonality. Mean reversion and seasonality are both observed in the soybean market. The empirical analysis lends strong support to the model.
    Keywords: G13 - Contingent Pricing ; Futures Pricing, Q11 - Aggregate Supply and Demand Analysis ; Prices
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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  • 9
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    An International Ki67 Reproducibility Study (2013)
    Oxford University Press
    Details
    Publication Date: 2013-12-20
    Description: Background In breast cancer, immunohistochemical assessment of proliferation using the marker Ki67 has potential use in both research and clinical management. However, lack of consistency across laboratories has limited Ki67’s value. A working group was assembled to devise a strategy to harmonize Ki67 analysis and increase scoring concordance. Toward that goal, we conducted a Ki67 reproducibility study. Methods Eight laboratories received 100 breast cancer cases arranged into 1-mm core tissue microarrays—one set stained by the participating laboratory and one set stained by the central laboratory, both using antibody MIB-1. Each laboratory scored Ki67 as percentage of positively stained invasive tumor cells using its own method. Six laboratories repeated scoring of 50 locally stained cases on 3 different days. Sources of variation were analyzed using random effects models with log2-transformed measurements. Reproducibility was quantified by intraclass correlation coefficient (ICC), and the approximate two-sided 95% confidence intervals (CIs) for the true intraclass correlation coefficients in these experiments were provided. Results Intralaboratory reproducibility was high (ICC = 0.94; 95% CI = 0.93 to 0.97). Interlaboratory reproducibility was only moderate (central staining: ICC = 0.71, 95% CI = 0.47 to 0.78; local staining: ICC = 0.59, 95% CI = 0.37 to 0.68). Geometric mean of Ki67 values for each laboratory across the 100 cases ranged 7.1% to 23.9% with central staining and 6.1% to 30.1% with local staining. Factors contributing to interlaboratory discordance included tumor region selection, counting method, and subjective assessment of staining positivity. Formal counting methods gave more consistent results than visual estimation. Conclusions Substantial variability in Ki67 scoring was observed among some of the world’s most experienced laboratories. Ki67 values and cutoffs for clinical decision-making cannot be transferred between laboratories without standardizing scoring methodology because analytical validity is limited.
    Electronic ISSN: 1460-2105
    Topics: Medicine
    Published by Oxford University Press
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  • 10
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    Promoting Quality and Evidence-Based Care in Early-Stage Breast Cancer Follow-up (2014)
    Oxford University Press
    Details
    Publication Date: 2014-04-10
    Description: Evidence-based guidelines for long-term follow-up of early-stage breast cancer patients developed by oncology societies in the United States and Europe recommend that breast cancer survivors undergo regular evaluation with history and physical examination, as well as annual mammography. Routine blood tests, circulating tumor markers, and/or surveillance imaging studies beyond mammography are not recommended in the absence of concerning symptoms or physical examination findings because of lack of supportive clinical evidence. Despite these guidelines, studies have shown that 20% to 40% of oncologists assess serum tumor markers as part of routine monitoring of early-stage breast cancer patients. As part of efforts to both address the financial challenges confronting the health-care system and optimize patient outcomes, the American Society of Clinical Oncology’s Cost of Care Task Force identified adherence to breast cancer surveillance guidelines as an opportunity to improve care and reduce cost. However, these recommendations are based on trials done in an era of outdated technology and limited therapeutic options. It is possible that recent improvements in diagnostics and treatments could make earlier detection of recurrent disease important for improving both survival and quality of life outcomes. Research is necessary to further inform optimal breast cancer follow-up strategies, which could impact these recommendations. At this time, outside of well-conducted clinical trials, there is no role for ordering routine serial blood or imaging tests in monitoring for recurrence in early-stage breast cancer patients.
    Electronic ISSN: 1460-2105
    Topics: Medicine
    Published by Oxford University Press
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