Abstract
Paleoclimate records suggest that a rapid major transient Antarctic glaciation occurred across the Oligocene‐Miocene transition (OMT; ca. 23 Ma; ~50‐m sea level equivalent in 200–300 kyr). ...Orbital forcing has long been cited as an important factor determining the timing of the OMT glacial event. A similar orbital configuration occurred 1.2 Myr prior to the OMT, however, and was not associated with a major climate event, suggesting that additional mechanisms play an important role in ice sheet growth and decay. To improve our understanding of the OMT, we present a boron isotope‐based CO
2
record between 22 and 24 Ma. This new record shows that δ
11
B/CO
2
was comparatively stable in the million years prior to the OMT glaciation and decreased by 0.7‰ (equivalent to a CO
2
increase of ~65 ppm) over ~300 kyr during the subsequent deglaciation. More data are needed, but we propose that the OMT glaciation was triggered by the same forces that initiated sustained Antarctic glaciation at the Eocene‐Oligocene transition: long‐term decline in CO
2
to a critical threshold and a superimposed orbital configuration favorable to glaciation (an eccentricity minimum and low‐amplitude obliquity change). When comparing the reconstructed CO
2
increase with estimates of δ
18
O
sw
during the deglaciation phase of the OMT, we find that the sensitivity of the cryosphere to CO
2
forcing is consistent with recent ice sheet modeling studies that incorporate retreat into subglacial basins via ice cliff collapse with modest CO
2
increase, with clear implications for future sea level rise.
Key Points
CO
2
levels were relatively low (~265 ppm;
ppm) and comparatively stable in the 500 kyr prior to and during the glaciation
CO
2
increased by ~65 ppm during the OMT deglaciation consistent with the latest generation of ice sheet models
The timing of the OMT glaciation is most likely controlled by both changes in CO
2
and favorable orbital forcing
Abstract
A major challenge in personalized healthcare is predicting how effective a drug treatment is. This is particularly the case in oncology, where there is a call for better therapy monitoring ...to maximize drug treatment effectiveness leading to improved patient survival and help reduce healthcare costs. GE152, a nuclear imaging agent under development at GE Healthcare, is being evaluated preclinically as a tool to assess therapeutic efficacy by detecting tumor apoptosis. GE152 is based on a 99mTechnetium radiolabelled peptide that shows nanomolar affinity for a specific cell death target, as demonstrated by studies using Biacore technology. Biodistribution using the murine lymphoma (EL4) tumour therapy model has shown increased tumor uptake and retention of GE152 following chemotherapy, with positive tumor:muscle and tumor:blood ratios. Correlation of tumor apoptosis levels (determined by caspase activity) with GE152 tumor retention suggest a trend of increasing agent retention with rising levels of apoptosis (GE152 retention in low apoptotic tumors is 4.9%ID/g; GE152 retention in high apoptotic tumors is 8.2%ID/g).Further validation of GE152 was carried out using an apoptosis-specific inducible cell death model whereby HT29 colorectal cancer cell xenografts engineered to inducibly express either a constitutively active form of caspase-3 (which causes synchronous cell death in vivo when exposed to doxycycline) or an inactive point mutant. GE152 demonstrated greater uptake in tumors undergoing apoptosis (3.6% ID/g) than in controls (1.2% ID/g), correlating with caspase activity levels (and subsequent apoptosis) as determined both enzymatically and by IHC and blood-borne biomarkers of cell death. These results are in agreement with preliminary preclinical imaging studies using SPECT/CT, where region of interest analysis has demonstrated increased post-therapy tumor retention of GE152. We are currently optimizing the performance of GE152 by assessing different radiolabelling precursors to improve imaging agent pharmacokinetics. In addition to the current 99mTechnetium-based approach, we are exploring 18F radiolabelling options that would allow expansion of the agent's utility to PET imaging.
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4294. doi:1538-7445.AM2012-4294
Abstract
The amplitude of climatic change, as recorded in the benthic oxygen isotope record, has varied throughout geological time. During the late Pleistocene, changes in the atmospheric ...concentration of carbon dioxide (CO
2
) are an important control on this amplitude of variability. The contribution of CO
2
to climate variability during the pre‐Quaternary however is unknown. Here we present a new boron isotope‐based CO
2
record for the transition into the middle Miocene Climatic Optimum (MCO) between 15.5 and 17 Myr that shows pronounced variability between 300 ppm and 500 ppm on a roughly 100 kyr time scale during the MCO. The CO
2
changes reconstructed for the Miocene are ~2 times larger in absolute terms (300 to 500 ppm compared to 180 to 280 ppm) than those associated with the late Pleistocene and ~15% larger in terms of climate forcing. In contrast, however, variability in the contemporaneous benthic oxygen isotope record (at ~1‰) is approximately two thirds the amplitude of that seen during the late Pleistocene. These observations indicate a lower overall sensitivity to CO
2
forcing for Miocene (Antarctic only) ice sheets than their late Pleistocene (Antarctic plus lower latitude northern hemisphere) counterparts. When our Miocene CO
2
record is compared to the estimated changes in contemporaneous δ
18
O
sw
(ice volume), they point to the existence of two reservoirs of ice on Antarctica. One of these reservoirs appears stable, while a second reservoir shows a level of dynamism that contradicts the results of coupled climate‐ice sheet model experiments given the CO
2
concentrations that we reconstruct.
Key Points
The middle Miocene is characterized by CO
2
variability between 300 and 500 ppm
The high‐amplitude CO
2
variability is matched by the changes in the paleorecords
Two regimes of ice volume‐CO
2
variability identified in middle Miocene
The amplitude of climatic change, as recorded in the benthic oxygen isotope record, has varied throughout geological time. During the late Pleistocene, changes in the atmospheric concentration of ...carbon dioxide (CO sub(2)) are an important control on this amplitude of variability. The contribution of CO sub(2) to climate variability during the pre-Quaternary however is unknown. Here we present a new boron isotope-based CO sub(2) record for the transition into the middle Miocene Climatic Optimum (MCO) between 15.5 and 17Myr that shows pronounced variability between 300ppm and 500ppm on a roughly 100kyr time scale during the MCO. The CO sub(2) changes reconstructed for the Miocene are 2 times larger in absolute terms (300 to 500ppm compared to 180 to 280ppm) than those associated with the late Pleistocene and 15% larger in terms of climate forcing. In contrast, however, variability in the contemporaneous benthic oxygen isotope record (at 1ppt) is approximately two thirds the amplitude of that seen during the late Pleistocene. These observations indicate a lower overall sensitivity to CO sub(2) forcing for Miocene (Antarctic only) ice sheets than their late Pleistocene (Antarctic plus lower latitude northern hemisphere) counterparts. When our Miocene CO sub(2) record is compared to the estimated changes in contemporaneous delta super(18)O sub(sw) (ice volume), they point to the existence of two reservoirs of ice on Antarctica. One of these reservoirs appears stable, while a second reservoir shows a level of dynamism that contradicts the results of coupled climate-ice sheet model experiments given the CO sub(2) concentrations that we reconstruct. Key Points * The middle Miocene is characterized by CO sub(2) variability between 300 and 500ppm * The high-amplitude CO sub(2) variability is matched by the changes in the paleorecords * Two regimes of ice volume-CO sub(2) variability identified in middle Miocene
The development of a permanent, stable ice sheet in East Antarctica happened during the middle Miocene, about 14 million years (Myr) ago. The middle Miocene therefore represents one of the distinct ...phases of rapid change in the transition from the “greenhouse” of the early Eocene to the “icehouse” of the present day. Carbonate carbon isotope records of the period immediately following the main stage of ice sheet development reveal a major perturbation in the carbon system, represented by the positive
δ
13
C excursion known as carbon maximum 6 (“CM6”), which has traditionally been interpreted as reflecting increased burial of organic matter and atmospheric
p
CO
2
drawdown. More recently, it has been suggested that the
δ
13
C excursion records a negative feedback resulting from the reduction of silicate weathering and an increase in atmospheric
p
CO
2
. Here we present high‐resolution multi‐proxy (alkenone carbon and foraminiferal boron isotope) records of atmospheric carbon dioxide and sea surface temperature across CM6. Similar to previously published records spanning this interval, our records document a world of generally low (~300 ppm) atmospheric
p
CO
2
at a time generally accepted to be much warmer than today. Crucially, they also reveal a
p
CO
2
decrease with associated cooling, which demonstrates that the carbon burial hypothesis for CM6 is feasible and could have acted as a positive feedback on global cooling.
Key Points
middle Miocene atmospheric CO2 is low (~300 ppm)
Atmospheric CO2 declined over carbon maximum 6
Organic carbon burial is a possible positive feedback for ice sheet growth
The development of a permanent, stable ice sheet in East Antarctica happened during the middle Miocene, about 14 million years (Myr) ago. The middle Miocene therefore represents one of the distinct ...phases of rapid change in the transition from the "greenhouse" of the early Eocene to the "icehouse" of the present day. Carbonate carbon isotope records of the period immediately following the main stage of ice sheet development reveal a major perturbation in the carbon system, represented by the positive delta super(13)C excursion known as carbon maximum 6 ("CM6"), which has traditionally been interpreted as reflecting increased burial of organic matter and atmospheric pCO sub(2) drawdown. More recently, it has been suggested that the delta super(13)C excursion records a negative feedback resulting from the reduction of silicate weathering and an increase in atmospheric pCO sub(2). Here we present high-resolution multi-proxy (alkenone carbon and foraminiferal boron isotope) records of atmospheric carbon dioxide and sea surface temperature across CM6. Similar to previously published records spanning this interval, our records document a world of generally low (~300ppm) atmospheric pCO sub(2) at a time generally accepted to be much warmer than today. Crucially, they also reveal a pCO sub(2) decrease with associated cooling, which demonstrates that the carbon burial hypothesis for CM6 is feasible and could have acted as a positive feedback on global cooling. Key Points * middle Miocene atmospheric CO2 is low (~300 ppm) * Atmospheric CO2 declined over carbon maximum 6 * Organic carbon burial is a possible positive feedback for ice sheet growth
Past warm periods provide an opportunity to evaluate climate models under extreme forcing scenarios, in particular high ( > 800 ppmv) atmospheric CO2 concentrations. Although a post hoc ...intercomparison of Eocene ( ∼ 50 Ma) climate model simulations and geological data has been carried out previously, models of past high-CO2 periods have never been evaluated in a consistent framework. Here, we present an experimental design for climate model simulations of three warm periods within the early Eocene and the latest Paleocene (the EECO, PETM, and pre-PETM). Together with the CMIP6 pre-industrial control and abrupt 4 × CO2 simulations, and additional sensitivity studies, these form the first phase of DeepMIP – the Deep-time Model Intercomparison Project, itself a group within the wider Paleoclimate Modelling Intercomparison Project (PMIP). The experimental design specifies and provides guidance on boundary conditions associated with palaeogeography, greenhouse gases, astronomical configuration, solar constant, land surface processes, and aerosols. Initial conditions, simulation length, and output variables are also specified. Finally, we explain how the geological data sets, which will be used to evaluate the simulations, will be developed.
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