The ESCAPE project: Energy-efficient Scalable Algorithms for Weather Prediction at Exascale

Abstract. In the simulation of complex multi-scale flows arising in weather and climate modelling, one of the biggest challenges is to satisfy strict service requirements in terms of time to solution and to satisfy budgetary constraints in terms of energy to solution, without compromising the accuracy and stability of the application. These simulations require algorithms that minimise the energy footprint along with the time required to produce a solution, maintain the physically required level of accuracy, are numerically stable, and are resilient in case of hardware failure. The European Centre for Medium-Range Weather Forecasts (ECMWF) led the ESCAPE (Energy-efficient Scalable Algorithms for Weather Prediction at Exascale) project, funded by Horizon 2020 (H2020) under the FET-HPC (Future and Emerging Technologies in High Performance Computing) initiative. The goal of ESCAPE was to develop a sustainable strategy to evolve weather and climate prediction models to next-generation computing technologies. The project partners incorporate the expertise of leading European regional forecasting consortia, university research, experienced high-performance computing centres, and hardware vendors. This paper presents an overview of the ESCAPE strategy: (i) identify domain-specific key algorithmic motifs in weather prediction and climate models (which we term Weather & Climate Dwarfs), (ii) categorise them in terms of computational and communication patterns while (iii) adapting them to different hardware architectures with alternative programming models, (iv) analyse the challenges in optimising, and (v) find alternative algorithms for the same scheme. The participating weather prediction models are the following: IFS (Integrated Forecasting System); ALARO, a combination of AROME (Application de la Recherche à l'Opérationnel à Meso-Echelle) and ALADIN (Aire Limitée Adaptation Dynamique Développement International); and COSMO–EULAG, a combination of COSMO (Consortium for Small-scale Modeling) and EULAG (Eulerian and semi-Lagrangian fluid solver). For many of the weather and climate dwarfs ESCAPE provides prototype implementations on different hardware architectures (mainly Intel Skylake CPUs, NVIDIA GPUs, Intel Xeon Phi, Optalysys optical processor) with different programming models. The spectral transform dwarf represents a detailed example of the co-design cycle of an ESCAPE dwarf. The dwarf concept has proven to be extremely useful for the rapid prototyping of alternative algorithms and their interaction with hardware; e.g. the use of a domain-specific language (DSL). Manual adaptations have led to substantial accelerations of key algorithms in numerical weather prediction (NWP) but are not a general recipe for the performance portability of complex NWP models. Existing DSLs are found to require further evolution but are promising tools for achieving the latter. Measurements of energy and time to solution suggest that a future focus needs to be on exploiting the simultaneous use of all available resources in hybrid CPU–GPU arrangements

Gal3 expression in DRGs is increased after SNL.

<p>(A) The mRNA level of gal3 is increased in DRGs of rats subjected to L5 SNL. Total RNA was extracted from the fifth lumbar dorsal horn sections and was subjected to real-time PCR to analyze the relative expression level of gal3 in each sample. Each sample was analyzed in triplicate. The 2^-ΔΔCt method was used to quantify the relative levels of gal3. β-actin was used as reference for mRNA. n = 10. *<i>p</i>< 0.05 vs sham, # <i>p</i>< 0.05 vs SNL group. (B and C) Western blot analysis of gal3 protein expression in the fifth lumbar dorsal horn sections in each sample.*<i>p</i>< 0.05 vs sham, # <i>p</i>< 0.05 vs SNL group.</p

MCP results in a decreased mechanicaland cold hypersensitivity.

<p>Mechanical (B) and cold (C) pain-related hypersensitivity developed after treatment with MCP (100 mg/kg/day) and Rapa (1 mg/kg/day) at the indicated time after surgery. n = 8. Data are expressed as mean ± SD. *<i>p</i>< 0.05 vs control, # <i>p</i>< 0.05 vs MCP group.</p

MCP inhibits SNL-induced activation of autophagy in spinal microglia.

<p>(A and B) Primary spinal microglial cells were isolatedfrom sham-, SNL-, and MCP-treated rats at day 10, and the autophagosome formation was visualized by assaying LC3 green puncta. Punctate staining is indicative for the redistribution of LC3 to autophagosomes. The average number of LC3 green puncta per cell with standard deviation for each group is presented. *<i>p</i>< 0.05 vs sham, # <i>p</i>< 0.05 vs SNL group. (C and D) Primary spinal microglial cells were isolated from sham-, SNL-, and MCP-treated rats at the indicated time, and LC3B protein levels were assayed using western blot analysis. <i>p</i>< 0.05 vs sham, # <i>p</i>< 0.05 vs SNL group. (E and F) Primary spinal microglial cells were isolated from sham-, SNL-, and MCP-treated rats at day 10, and the protein levels of p62 were assayed using western blot analysis. <i>p</i>< 0.05 vs sham, # <i>p</i>< 0.05 vs SNL group. (G-I) Microglial cells were isolated from sham-, SNL-, and MCP-treated rats at day 10, and the expression level of gal3 and autophagy activation was assayed using double-label immunofluorescence analysis. Scale bar = 50 μm.</p

MCP inhibits LPS-induced activation of autophagy in microglia.

<p>(A and B) Mixed microglial cultures isolated from sham rats were treated with LPS (0.5ng/μl) and MCP (1 μg/μl), and the autophagosome formation was visualized by assaying LC3 green puncta. The average number of LC3 green puncta per cell with standard deviation for each group is presented. *<i>p</i>< 0.05 vs control, # <i>p</i>< 0.05 vs LPS group. Mixed microglial cultures isolated from sham rats were treated with LPS (0.5ng/μl) MCP (1 μg/μl) or Rapa (500 nM), and LC3B protein levels (C and D) or p62 protein levels (E and F) were assayed using western blot analysis. *<i>p</i>< 0.05 vs control, # <i>p</i>< 0.05 vs LPS group.</p

Enzymatic Cleavage and Subsequent Facile Intramolecular Transcyclization for in Situ Fluorescence Detection of γ‑Glutamyltranspetidase Activities

γ-Glutamyltranspetidase (GGT) is a cell-membrane-bound enzyme which selectively catalyzes cleavage of the γ-glutamyl bond of glutathione (GSH). It has been identified to be overexpressed in a number of malignant tumor cells. Therefore, fluorescent probes for fast and selective detection of GGT activities are greatly needed. However, the majority of currently available GGT fluorescent probes based on direct conjugation of a γ-glutamyl group to a specific fluorophore generally has slow enzymatic kinetics due to bulky fluorophore too close to the enzyme’s active site. Moreover, the uncaged fluorophore with a free amine group might undergo oxidation or other enzymatic transformation and resulted in a complicated time-dependent fluorescence response. Herein, we reported design of a novel fluorescent GGT probe <b>NM-GSH</b> (<b>2</b>), which incorporated a fast intramolecular transcyclization cascade for rapid detection of GGT activities after enzymatic cleavage of the γ-glutamyl group. This design strategy allows introduction of bulky 1,8-naphthalimide fluorophore with improved enzymatic kinetics and lowered detection limit. The transcyclized product <b>4</b> gives more than 200-fold fluorescence increment. The probe <b>NM-GSH</b> showed both good selectivity and fast detection of GGT activities with the detection limit as low as 0.21 mU/mL. In addition, the fluorescent product <b>4</b> contains no free amine group and is more stable for detection. Most importantly, cell imaging studies showed that the transcyclized product <b>4</b> was enriched in lysosomes for selectively lighting up GGT-overexpressed ovarian cancer cells (OVCAR5) but not normal cells (HUVEC), indicating <b>NM-GSH</b>’s potentials as an imaging agent in cancer diagnosis and treatment