A new regional climate model for POLAR-CORDEX : evaluation of a 30-year hindcast with COSMO-CLM2 over Antarctica

Continent-wide climate information over the Antarctic Ice Sheet (AIS) is important to obtain accurate information of present climate and reduce uncertainties of the ice sheet mass balance response and resulting global sea level rise to future climate change. In this study, the COSMO-CLM2 Regional Climate Model is applied over the AIS and adapted for the specific meteorological and climatological conditions of the region. A 30-year hindcast was performed and evaluated against observational records consisting of long-term ground-based meteorological observations, automatic weather stations, radiosoundings, satellite records, stake measurements and ice cores. Reasonable agreement regarding the surface and upper-air climate is achieved by the COSMO-CLM2 model, comparable to the performance of other state-of-the-art climate models over the AIS. Meteorological variability of the surface climate is adequately simulated, and biases in the radiation and surface mass balance are small. The presented model therefore contributes as a new member to the COordinated Regional Downscaling EXperiment project over the AIS (POLAR-CORDEX) and the CORDEX-CORE initiative

Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases.

BACKGROUND: Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics. METHODS: We used our newly developed sticky siRNA-based technology delivered with linear polyethyleneimine (PEI) to inhibit the expression of survivin and cyclin B1 both in vitro and in vivo, and addressed the effect of this inhibition on B16-F10 murine melanoma tumor development. RESULTS: We confirm that survivin and cyclin B1 downregulation through a RNA interference mechanism induces a blockage of the cell cycle as well as impaired proliferation of B16-F10 cells in vitro. Most importantly, PEI-mediated systemic delivery of sticky siRNAs against survivin and cyclin B1 efficiently blocks growth of established subcutaneaous B16-F10 tumors as well as formation and dissemination of melanoma lung metastases. In addition, we highlight that inhibition of survivin expression increases the effect of doxorubicin on lung B16-F10 metastasis growth inhibition. CONCLUSION: PEI-mediated delivery of sticky siRNAs targeting genes involved in tumor progression such as survivin and cyclin B1, either alone or in combination with chemotherapeutic drugs, represents a promising strategy for melanoma treatment

Evaluation of the CloudSat surface snowfall product over Antarctica using ground-based precipitation radars

In situ observations of snowfall over the Antarctic Ice Sheet are scarce. Currently, continent-wide assessments of snowfall are limited to information from the Cloud Profiling Radar on board the CloudSat satellite, which has not been evaluated up to now. In this study, snowfall derived from CloudSat is evaluated using three ground-based vertically profiling 24&thinsp;GHz precipitation radars (Micro Rain Radars: MRRs). Firstly, using the MRR long-term measurement records, an assessment of the uncertainty caused by the low temporal sampling rate of CloudSat (one revisit per 2.1 to 4.5 days) is performed. The 10–90th-percentile temporal sampling uncertainty in the snowfall climatology varies between 30&thinsp;% and 40&thinsp;% depending on the latitudinal location and revisit time of CloudSat. Secondly, an evaluation of the snowfall climatology indicates that the CloudSat product, derived at a resolution of 1∘ latitude by 2∘ longitude, is able to accurately represent the snowfall climatology at the three MRR sites (biases&thinsp;&lt;&thinsp;15&thinsp;%), outperforming ERA-Interim. For coarser and finer resolutions, the performance drops as a result of higher omission errors by CloudSat. Moreover, the CloudSat product does not perform well in simulating individual snowfall events. Since the difference between the MRRs and the CloudSat climatology are limited and the temporal uncertainty is lower than current Climate Model Intercomparison Project Phase 5 (CMIP5) snowfall variability, our results imply that the CloudSat product is valuable for climate model evaluation purposes.</p

Performance of Pyridylthiourea-Polyethylenimine Polyplex for siRNA-Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models

Medical application of siRNAs relies on methods for delivering nucleic acids into the cytosol. Synthetic carriers, which assemble with nucleic acids into delivery systems, show promises for cancer therapy but efficiency remains to be improved. In here, the effectiveness of pyridylthiourea‐polyethylenimine (πPEI), a siRNA carrier that favors both polyplex disassembly and endosome rupture upon sensing the acidic endosomal environment, in 3 experimental models of hepatocellular cancer is tested. The πPEI‐assisted delivery of a siRNA targeting the polo‐like kinase 1 into Huh‐7 monolayer produces a 90% cell death via a demonstrated RNA interference mechanism. Incubation of polyplex with Huh‐7 spheroids leads to siRNA delivery into the superficial first cell layer and a 60% reduction in spheroid growth compared to untreated controls. Administration of polyplexes into mice bearing subcutaneous implanted Huh‐7Luc tumors results in a reduced tumor progression, similar to the one observed in the spheroid model. Altogether, these results support the in vivo use of synthetic and dedicated polymers for increasing siRNA‐mediated gene knockdown, and their clinical promise in cancer therapeutics