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  • 1
    Publication Date: 2022-05-25
    Description: Assessing the skill of the Atlantic meridional overturning circulation (AMOC) in decadal hindcasts (i.e. retrospective predictions) is hampered by a lack of obser- vations for verification. Models are therefore needed to reconstruct the historical AMOC variability. Here we show that ten recent oceanic syntheses provide a common signal of AMOC variability at 45°N, with an increase from the 1960s to the mid-1990s and a decrease thereafter although they disagree on the exact magnitude. This signal corre- lates with observed key processes such as the North Atlantic Oscillation, sub-polar gyre strength, Atlantic sea surface temperature dipole, and Labrador Sea convection that are thought to be related to the AMOC. Furthermore, we find potential predictability of the mid-latitude AMOC for the first 3–6 year means when we validate decadal hindcasts for the past 50 years against the multi-model signal. However, this predictability is not found in models driven only by external radiative changes, demonstrating the need for initialization of decadal climate predictions.
    Description: Published
    Description: 775-785
    Description: 3.7. Dinamica del clima e dell'oceano
    Description: JCR Journal
    Description: restricted
    Keywords: Decadal prediction 􏰁 Atlantic MOC 􏰁 Predictability 􏰁 Multi-model comparison ; 01. Atmosphere::01.01. Atmosphere::01.01.02. Climate ; 03. Hydrosphere::03.01. General::03.01.03. Global climate models ; 03. Hydrosphere::03.03. Physical::03.03.03. Interannual-to-decadal ocean variability
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
    Publication Date: 2019-09-23
    Description: We investigate the respective role of variations in subpolar deep water formation and Nordic Seas overflows for the decadal to multidecadal variability of the Atlantic meridional overturning circulation (AMOC). This is partly done by analysing long (order of 1000 years) control simulations with five coupled climate models. For all models, the maximum influence of variations in subpolar deep water formation is found at about 45° N, while the maximum influence of variations in Nordic Seas overflows is rather found at 55 to 60° N. Regarding the two overflow branches, the influence of variations in the Denmark Strait overflow is, for all models, substantially larger than that of variations in the overflow across the Iceland–Scotland Ridge. The latter might, however, be underestimated, as the models in general do not realistically simulate the flow path of the Iceland–Scotland overflow water south of the Iceland–Scotland Ridge. The influence of variations in subpolar deep water formation is, on multimodel average, larger than that of variations in the Denmark Strait overflow. This is true both at 45° N, where the maximum standard deviation of decadal to multidecadal AMOC variability is located for all but one model, and at the more classical latitude of 30° N. At 30° N, variations in subpolar deep water formation and Denmark Strait overflow explain, on multimodel average, about half and one-third respectively of the decadal to multidecadal AMOC variance. Apart from analysing multimodel control simulations, we have performed sensitivity experiments with one of the models, in which we suppress the variability of either subpolar deep water formation or Nordic Seas overflows. The sensitivity experiments indicate that variations in subpolar deep water formation and Nordic Seas overflows are not completely independent. We further conclude from these experiments that the decadal to multidecadal AMOC variability north of about 50° N is mainly related to variations in Nordic Seas overflows. At 45° N and south of this latitude, variations in both subpolar deep water formation and Nordic Seas overflows contribute to the AMOC variability, with neither of the processes being very dominant compared to the other.
    Type: Article , PeerReviewed , info:eu-repo/semantics/article
    Format: text
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  • 3
    Publication Date: 2020-02-06
    Description: A set of ensemble integrations from the Coupled Model Intercomparison Project phase 5, with historical forcing plus RCP4.5 scenario, are used to explore if state-of-the-art climate models are able to simulate previously reported linkages between sea-ice concentration (SIC) anomalies over the eastern Arctic, namely in the Greenland–Barents–Kara Seas, and lagged atmospheric circulation that projects on the North Atlantic Oscillation (NAO)/Arctic Oscillation (AO). The study is focused on variability around the long-term trends, so that all anomalies are detrended prior to analysis; the period of study is 1979–2013. The model linkages are detected by applying maximum covariance analysis. As also found in observational data, all the models considered here show a statistically significant link with sea-ice reduction over the eastern Arctic followed by a negative NAO/AO-like pattern. If the simulated relationship is found at a lag of one month, the results suggest that a stratospheric pathway could be at play as the driving mechanism; in observations this is preferentially shown for SIC in November. The interference of a wave-like anomaly over Eurasia, accompanying SIC changes, with the climatological wave pattern appears to be key in setting the mediating role of the stratosphere. On the other hand, if the simulated relationship is found at a lag of two months, the results suggest that tropospheric dynamics are dominant, presumably due to transient eddy feedback; in observations this is preferentially shown for SIC in December. The results shown here and previous evidence from atmosphere-only experiments emphasize that there could be a detectable influence of eastern Arctic SIC variability on mid-latitude atmospheric circulation anomalies. Even if the mechanisms are robust among the models, the timing of the simulated linkages strongly depends on the model and does not generally mimic the observational ones. This implies that the atmospheric sensitivity to sea-ice changes largely depends on the mean-flow and parameterizations, which could lead to misleading conclusions elsewhere if a multi-model ensemble-mean approach is adopted. It might also represent an important source of uncertainty in climate prediction and projection. Modelling efforts are hence further required to improve representation of the background atmospheric circulation and reduce biases, in order to attain more accurate covariability.
    Type: Article , PeerReviewed , info:eu-repo/semantics/article
    Format: text
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  • 4
    Publication Date: 2017-07-27
    Description: Extremely large volcanic eruptions have been linked to global climate change, biotic turnover, and, for the Younger Toba Tuff (YTT) eruption 74,000 years ago, near-extinction of modern humans. One of the largest uncertainties of the climate effects involves evolution and growth of aerosol particles. A huge atmospheric concentration of sulfate causes higher collision rates, larger particle sizes, and rapid fall out, which in turn greatly affects radiative feedbacks. We address this key process by incorporating the effects of aerosol microphysical processes into an Earth System Model. The temperature response is shorter (9–10 years) and three times weaker (−3.5 K at maximum globally) than estimated before, although cooling could still have reached −12 K in some midlatitude continental regions after one year. The smaller response, plus its geographic patchiness, suggests that most biota may have escaped threshold extinction pressures from the eruption.
    Type: Article , PeerReviewed
    Format: text
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  • 5
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    AMS (American Meteorological Society)
    In:  Journal of Climate, 21 . pp. 4691-4709.
    Publication Date: 2019-09-23
    Description: The relative impact of the subtropical North and South Pacific Oceans on the tropical Pacific climate mean state and variability is estimated using an ocean–atmosphere–sea ice coupled general circulation model. Tailored experiments are performed in which the model is forced by idealized sea surface temperature anomalies (SSTAs) in the subtropics of both hemispheres. The main results of this study suggest that subtropical South Pacific climate variations play a dominant role in tropical Pacific decadal variability and in the decadal modulation of El Niño–Southern Oscillation (ENSO). In response to a 2°C warming in the subtropical South Pacific, the equatorial Pacific SST increases by about 0.6°C, approximately 65% larger than the change in the North Pacific experiment. The subtropics affect equatorial SST mainly through atmosphere–mixed layer interactions in the South Pacific experiments; the response is mostly accomplished within a decade. The “oceanic tunnel” dominates in the North Pacific experiments; the response takes at least 100 yr to be accomplished. Similar sensitivity experiments conducted with the stand-alone atmosphere model showed that both air–sea interactions and ocean dynamics are crucial in shaping the tropical climate response. The statistics of ENSO exhibit significant changes in amplitude and frequency in response to a warming/cooling of the subtropical South Pacific: a 2°C warming (cooling) of subtropical South Pacific SST reduces (increases) the interannual standard deviation by about 30% (20%) and shortens (lengthens) the ENSO period. The simulated changes in the equatorial zonal SST gradient are the main contributor to the modulation of ENSO variability. The simulated intensification (weakening) of the annual cycle in response to an enhanced warming (cooling) in subtropical South Pacific partly explains the shifts in frequency, but may also lead to a weaker (stronger) ENSO. The subtropical North Pacific thermal forcing did not change the statistical properties of ENSO as strongly.
    Type: Article , PeerReviewed
    Format: text
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  • 6
    Publication Date: 2014-09-03
    Description: Emerging results indicate that cancer stem–like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem–like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem–like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem–like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH+ ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH+ cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem–like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. Cancer Res; 74(17); 4922–36. ©2014 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
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  • 7
    Publication Date: 2015-10-02
    Description: Purpose: Aggressive pancreatic cancer is commonly associated with a dense desmoplastic stroma, which forms a protective niche for cancer cells. The objective of the study was to determine the functions of tissue transglutaminase (TG2), a Ca 2+ -dependent enzyme that cross-links proteins through transamidation and is abundantly expressed by pancreatic cancer cells in the pancreatic stroma. Experimental Design: Orthotopic pancreatic xenografts and coculture systems tested the mechanisms by which the enzyme modulates tumor–stroma interactions. Results: We show that TG2 secreted by cancer cells effectively molds the stroma by cross-linking collagen, which, in turn, activates fibroblasts and stimulates their proliferation. The stiff fibrotic stromal reaction conveys mechanical cues to cancer cells, leading to activation of the YAP/TAZ transcription factors, promoting cell proliferation and tumor growth. Stable knockdown of TG2 in pancreatic cancer cells leads to decreased size of pancreatic xenografts. Conclusions: Taken together, our results demonstrate that TG2 secreted in the tumor microenvironment orchestrates the cross-talk between cancer cells and stroma fundamentally affecting tumor growth. Our study supports TG2 inhibition in the pancreatic stroma as a novel strategy to block pancreatic cancer progression. Clin Cancer Res; 21(19); 4482–93. ©2015 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 8
    Publication Date: 2013-08-02
    Description: Tissue transglutaminase (TG2) is a multifunctional enzyme involved in protein cross-linking and cell adhesion to fibronectin (FN). In cancer, TG2 induces an epithelial to mesenchymal transition, contributing to metastasis. Because cadherins bind β-catenin at cell-cell junctions, disruption of adherens junctions destabilizes cadherin-catenin complexes. The goal of the present study was to analyze whether and how TG2 interacts with and regulates β-catenin signaling in ovarian cancer (OC) cells. We observed a significant correlation between TG2 and β-catenin expression levels in OC cells and tumors. TG2 augmented Wnt/β-catenin signaling, as evidenced by enhanced β-catenin transcriptional activity, inducing transcription of target genes cyclin D1 and c-Myc. By promoting integrin-mediated cell adhesion to FN, TG2 physically associates with and recruits c-Src, which in turn phosphorylates β-catenin at Tyr 654 , releasing it from E-cadherin and rendering it available for transcriptional regulation. By interacting with FN and enhancing β-catenin signaling, complexed TG2 stimulates OC cell proliferation. In summary, our data demonstrate that TG2 regulates β-catenin expression and function in OC cells and define the c-Src-dependent mechanism through which this occurs.—Condello, S., Cao, L., Matei, D. Tissue transglutaminase regulates β-catenin signaling through a c-Src-dependent mechanism.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
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  • 9
    Publication Date: 2014-12-16
    Description: Purpose: To investigate SGI-110 as a "chemosensitizer" in ovarian cancer and to assess its effects on tumor suppressor genes (TSG) and chemoresponsiveness-associated genes silenced by DNA methylation in ovarian cancer. Experimental Design: Several ovarian cancer cell lines were used for in vitro and in vivo platinum resensitization studies. Changes in DNA methylation and expression levels of TSG and other cancer-related genes in response to SGI-110 were measured by pyrosequencing and RT-PCR. Results: We demonstrate in vitro that SGI-110 resensitized a range of platinum-resistant ovarian cancer cells to cisplatin (CDDP) and induced significant demethylation and reexpression of TSG, differentiation-associated genes, and putative drivers of ovarian cancer cisplatin resistance. In vivo , SGI-110 alone or in combination with CDDP was well tolerated and induced antitumor effects in ovarian cancer xenografts. Pyrosequencing analyses confirmed that SGI-110 caused both global ( LINE1 ) and gene-specific hypomethylation in vivo , including TSGs ( RASSF1A ), proposed drivers of ovarian cancer cisplatin resistance ( MLH1 and ZIC1 ), differentiation-associated genes ( HOXA10 and HOXA11 ), and transcription factors ( STAT5B ). Furthermore, DNA damage induced by CDDP in ovarian cancer cells was increased by SGI-110, as measured by inductively coupled plasma-mass spectrometry analysis of DNA adduct formation and repair of cisplatin-induced DNA damage. Conclusions: These results strongly support further investigation of hypomethylating strategies in platinum-resistant ovarian cancer. Specifically, SGI-110 in combination with conventional and/or targeted therapeutics warrants further development in this setting. Clin Cancer Res; 20(24); 6504–16. ©2014 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 10
    Publication Date: 2014-12-02
    Description: Purpose: Endoglin, an endothelial cell membrane receptor expressed on angiogenic tumor vessels, is essential for angiogenesis and upregulated in the setting of VEGF inhibition. TRC105 is an anti-endoglin IgG1 monoclonal antibody that potentiates VEGF inhibitors in preclinical models. This study assessed safety, pharmacokinetics, and antitumor activity of TRC105 in combination with bevacizumab. Experimental Design: Patients ( n = 38) with advanced solid tumors, Eastern Cooperative Group performance status 0–1, and normal organ function were treated with escalating doses of TRC105 plus bevacizumab until disease progression or unacceptable toxicity using a standard 3 + 3 phase I design. Results: TRC105 and bevacizumab were well tolerated at their recommended single-agent doses (10 mg/kg) when the initial dose of TRC105 was delayed by one week and divided over 2 days to limit the frequency of headache. The concurrent administration of bevacizumab and TRC105 did not otherwise potentiate known toxicities of TRC105 or bevacizumab. Hypertension and proteinuria were observed, though not at rates expected for single-agent bevacizumab. Several patients who had previously progressed on bevacizumab or VEGF receptor tyrosine kinase inhibitor (VEGFR TKI) treatment experienced reductions in tumor volume, including two partial responses by RECIST, and 6 remained without progression for longer periods than during their prior VEGF inhibitor therapy. Conclusions: TRC105 was well tolerated with bevacizumab and clinical activity was observed in a VEGF inhibitor–refractory population. Ongoing clinical trials are testing TRC105 in combination with bevacizumab in glioblastoma and with VEGFR TKIs in renal cell carcinoma, hepatocellular carcinoma, and soft tissue sarcoma. Clin Cancer Res; 20(23); 5918–26. ©2014 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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