Dataset Information

Enhancing the ENSO Predictability beyond the Spring Barrier.

ABSTRACT: El Niño-Southern Oscillation (ENSO) is the dominant interseasonal-interannual variability in the tropical Pacific and substantial efforts have been dedicated to predicting its occurrence and variability because of its extensive global impacts. However, ENSO predictability has been reduced in the 21st century, and the impact of extratropical atmosphere on the tropics has intensified during the past 2 decades, making the ENSO more complicated and harder to predict. Here, by combining tropical preconditions/ocean-atmosphere interaction with extratropical precursors, we provide a novel approach to noticeably increase the ENSO prediction skill beyond the spring predictability barrier. The success of increasing the prediction skill results mainly from the longer lead-time of the extratropical-tropical ocean-to-atmosphere interaction process, especially for the first 2 decades of the 21st century.

SUBMITTER: Chen HC

PROVIDER: S-EPMC6976663 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Enhancing the ENSO Predictability beyond the Spring Barrier.

Chen Han-Ching HC Tseng Yu-Heng YH Hu Zeng-Zhen ZZ Ding Ruiqiang R

Scientific reports 20200122 1

El Niño-Southern Oscillation (ENSO) is the dominant interseasonal-interannual variability in the tropical Pacific and substantial efforts have been dedicated to predicting its occurrence and variability because of its extensive global impacts. However, ENSO predictability has been reduced in the 21<sup>st</sup> century, and the impact of extratropical atmosphere on the tropics has intensified during the past 2 decades, making the ENSO more complicated and harder to predict. Here, by combining tr ...[more]

PMID: 31969614

Similar Datasets

Project description:Pretargeting is a powerful nuclear imaging strategy to achieve enhanced imaging contrast for nanomedicines and reduce the radiation burden to healthy tissue. Pretargeting is based on bioorthogonal chemistry. The most attractive reaction for this purpose is currently the tetrazine ligation, which occurs between trans-cyclooctene (TCO) tags and tetrazines (Tzs). Pretargeted imaging beyond the blood-brain barrier (BBB) is challenging and has not been reported thus far. In this study, we developed Tz imaging agents that are capable of ligating in vivo to targets beyond the BBB. We chose to develop 18F-labeled Tzs as they can be applied to positron emission tomography (PET) - the most powerful molecular imaging technology. Fluorine-18 is an ideal radionuclide for PET due to its almost ideal decay properties. As a non-metal radionuclide, fluorine-18 also allows for development of Tzs with physicochemical properties enabling passive brain diffusion. To develop these imaging agents, we applied a rational drug design approach. This approach was based on estimated and experimentally determined parameters such as the BBB score, pretargeted autoradiography contrast, in vivo brain influx and washout as well as on peripheral metabolism profiles. From 18 initially developed structures, five Tzs were selected to be tested for their in vivo click performance. Whereas all selected structures clicked in vivo to TCO-polymer deposited into the brain, [18F]18 displayed the most favorable characteristics with respect to brain pretargeting. [18F]18 is our lead compound for future pretargeted neuroimaging studies based on BBB-penetrant monoclonal antibodies. Pretargeting beyond the BBB will allow us to image targets in the brain that are currently not imageable, such as soluble oligomers of neurodegeneration biomarker proteins. Imaging of such currently non-imageable targets will allow early diagnosis and personalized treatment monitoring. This in turn will accelerate drug development and greatly benefit patient care.

Project description:Pretargeting is a promising nuclear imaging technique that allows for the usage of antibodies (Abs) with enhanced imaging contrast and reduced patient radiation burden. It is based on bioorthogonal chemistry with the tetrazine ligation-a reaction between trans-cyclooctenes (TCOs) and tetrazines (Tzs)-currently being the most popular reaction due to its high selectivity and reactivity. As Abs can be designed to bind specifically to currently 'undruggable' targets such as protein isoforms or oligomers, which play a crucial role in neurodegenerative diseases, pretargeted imaging beyond the BBB is highly sought after, but has not been achieved yet. A challenge in this respect is that large molecules such as Abs show poor brain uptake. Uptake can be increased by receptor mediated transcytosis; however, it is largely unknown if the achieved brain concentrations are sufficient for pretargeted imaging. In this study, we investigated whether the required concentrations are feasible to reach. As a model Ab, we used the bispecific anti-amyloid beta (Aβ) anti-transferrin receptor (TfR) Ab 3D6scFv8D3 and conjugated it to a different amount of TCOs per Ab and tested different concentrations in vitro. With this model in hand, we estimated the minimum required TCO concentration to achieve a suitable contrast between the high and low binding regions. The estimation was carried out using pretargeted autoradiography on brain sections of an Alzheimer's disease mouse model. Biodistribution studies in wild-type (WT) mice were used to correlate how different TCO/Ab ratios alter the brain uptake. Pretargeted autoradiography showed that increasing the number of TCOs as well as increasing the TCO-Ab concentration increased the imaging contrast. A minimum brain concentration of TCOs for pretargeting purposes was determined to be 10.7 pmol/g in vitro. Biodistribution studies in WT mice showed a brain uptake of 1.1% ID/g using TCO-3D6scFv8D3 with 6.8 TCO/Ab. According to our estimations using the optimal parameters, pretargeted imaging beyond the BBB is not a utopia. Necessary brain TCO concentrations can be reached and are in the same order of magnitude as required to achieve sufficient contrast. This work gives a first estimate that pretargeted imaging is indeed possible with antibodies. This could allow the imaging of currently 'undruggable' targets and therefore be crucial to monitor (e.g., therapies for intractable neurodegenerative diseases).

Dataset Information

Enhancing the ENSO Predictability beyond the Spring Barrier.

Publications

Enhancing the ENSO Predictability beyond the Spring Barrier.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets