Global meteorology data are now widely used in various areas, but one of its applications, weather analogues, still require exhaustive searches on the whole historical data. We present two optimisations for the state-...Global meteorology data are now widely used in various areas, but one of its applications, weather analogues, still require exhaustive searches on the whole historical data. We present two optimisations for the state-of-the-art weather analogue search algorithms: a parallelization and a heuristic search. The heuristic search (NDRank) limits of the final number of results and does initial searches on a lower resolution dataset to find candidates that, in the second phase, are locally validated. These optimisations were deployed in the Cloud and evaluated with ERA5 data from ECMWF. The proposed parallelization attained speedups close to optimal, and NDRank attains speedups higher than 4. NDRank can be applied to any parallel search, adding similar speedups. A substantial number of executions returned a set of analogues similar to the existing exhaustive search and most of the remaining results presented a numerical value difference lower than 0.1%. The results demonstrate that it is now possible to search for weather analogues in a faster way (even compared with parallel searches) with results with little to no error. Furthermore, NDRank can be applied to existing exhaustive searches, providing faster results with small reduction of the precision of the results.展开更多
Taxane efficacy in triple negative breast cancer(TNBC)is limited by insufficient tumor accumulation and severe off-target effects.Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this dru...Taxane efficacy in triple negative breast cancer(TNBC)is limited by insufficient tumor accumulation and severe off-target effects.Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug.Here,1,000 nm×400 nm discoidal polymeric nanoconstructs(DPN)encapsulating docetaxel(DTXL)and the near infrared compound Iipid-Cy5 were engineered.DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol)template with a polymer mixture comprising poly(lactic-co-glycolic acid)(PLGA)and poly(ethylene glycol)diacrylate(PEG-DA)chains together with therapeutic and imaging agents.The resulting“multi-passage”DPN exhibited higher DTXL loading,Iipid-Cy5 stability,and stiffness as compared to the conventional"single-passage"approach.Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof.Empty DPN had no toxicity on TNBC cells,whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL(IC_(50)=2.6 nM±1.0 nM vs.7.0 nM±1.09 nM at 72 h).In orthotopic murine models,DPN accumulated in TNBC more efficiently than free-DTXL.With only 2 mg/kg DTXL,intravenously administered every 2 days for a total of 13 treatments,DTXL-DPN induced tumor regression and were associated to an overall 80%survival rate as opposed to a 30%survival rate for free-DTXL,at 120 days.All untreated mice succumbed before 90 days.Collectively,this data demonstrates that vascular confined multi-passage DPN,biomimicking the behavior of circulating platelets,can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.展开更多
基金the Fundação para a Ciência e a Tecnologia[UIDB/50021/2020].
文摘Global meteorology data are now widely used in various areas, but one of its applications, weather analogues, still require exhaustive searches on the whole historical data. We present two optimisations for the state-of-the-art weather analogue search algorithms: a parallelization and a heuristic search. The heuristic search (NDRank) limits of the final number of results and does initial searches on a lower resolution dataset to find candidates that, in the second phase, are locally validated. These optimisations were deployed in the Cloud and evaluated with ERA5 data from ECMWF. The proposed parallelization attained speedups close to optimal, and NDRank attains speedups higher than 4. NDRank can be applied to any parallel search, adding similar speedups. A substantial number of executions returned a set of analogues similar to the existing exhaustive search and most of the remaining results presented a numerical value difference lower than 0.1%. The results demonstrate that it is now possible to search for weather analogues in a faster way (even compared with parallel searches) with results with little to no error. Furthermore, NDRank can be applied to existing exhaustive searches, providing faster results with small reduction of the precision of the results.
基金supported by the European Research Council,under the European Unions Seventh Framework Programme(FP7/2007-2013)/ERC grant agreement No.616695,by the Italian Association for Cancer Research(AIRC)under the individual investigator grant No.17664,and by the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No.754490.
文摘Taxane efficacy in triple negative breast cancer(TNBC)is limited by insufficient tumor accumulation and severe off-target effects.Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug.Here,1,000 nm×400 nm discoidal polymeric nanoconstructs(DPN)encapsulating docetaxel(DTXL)and the near infrared compound Iipid-Cy5 were engineered.DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol)template with a polymer mixture comprising poly(lactic-co-glycolic acid)(PLGA)and poly(ethylene glycol)diacrylate(PEG-DA)chains together with therapeutic and imaging agents.The resulting“multi-passage”DPN exhibited higher DTXL loading,Iipid-Cy5 stability,and stiffness as compared to the conventional"single-passage"approach.Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof.Empty DPN had no toxicity on TNBC cells,whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL(IC_(50)=2.6 nM±1.0 nM vs.7.0 nM±1.09 nM at 72 h).In orthotopic murine models,DPN accumulated in TNBC more efficiently than free-DTXL.With only 2 mg/kg DTXL,intravenously administered every 2 days for a total of 13 treatments,DTXL-DPN induced tumor regression and were associated to an overall 80%survival rate as opposed to a 30%survival rate for free-DTXL,at 120 days.All untreated mice succumbed before 90 days.Collectively,this data demonstrates that vascular confined multi-passage DPN,biomimicking the behavior of circulating platelets,can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.
