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At least 289 records · Page 16

L–malic acid production from xylose by engineered Saccharomyces cerevisiae

L-malic acid is widely used in the food, chemical, and pharmaceutical industries. Here, we report on production of malic acid from xylose, the second most abundant sugar in lignocellulosic hydrolysates, by engineered Saccharomyces cerevisiae. To enable malic acid production in a xylose-assimilating S. cerevisiae, we overexpressed PYC1 and PYC2, coding for pyruvate carboxylases, a truncated MDH3 coding for malate dehydrogenase, and SpMAE1, coding for a Schizosaccharomyces pombe malate transporter. Additionally, both the ethanol and glycerol-producing pathways were blocked to enhance malic acid production. The resulting strain produced malic acid from both glucose and xylose, but it produced much higher titers of malic acid from xylose than glucose. Interestingly, the engineered strain had higher malic acid yield from lower concentrations (10 g L –1 ) of xylose, with no ethanol production, than from higher xylose concentrations (20 and 40 g L –1 ). As such, a fed-batch culture maintaining xylose concentrations at low levels was conducted and 61.2 g L –1 of malic acid was produced, with a productivity of 0.32 g L –1 h. Furthermore, these results represent successful engineering of S. cerevisiae for the production of malic acid from xylose, confirming that that xylose offers the efficient production of various biofuels and chemicals by engineered S. cerevisiae.

59 BASIC BIOLOGICAL SCIENCES↗

StaNdaRT: a repository of standardised test models and outputs for supernova radiative transfer

We present the first results of a comprehensive supernova (SN) radiative-transfer (RT) code-comparison initiative (StaNdaRT), where the emission from the same set of standardised test models is simulated by currently used RT codes. We ran a total of ten codes on a set of four benchmark ejecta models of Type Ia SNe. We consider two sub-Chandrasekhar-mass (M tot = 1.0 M ⊙ ) toy models with analytic density and composition profiles and two Chandrasekhar-mass delayed-detonation models that are outcomes of hydrodynamical simulations. We adopt spherical symmetry for all four models. The results of the different codes, including the light curves, spectra, and the evolution of several physical properties as a function of radius and time are provided in electronic form in a standard format via a public repository. We also include the detailed test model profiles and several Python scripts for accessing and presenting the input and output files. We also provide the code used to generate the toy models studied here. In this paper, we describe the test models, radiative-transfer codes, and output formats in detail, and provide access to the repository. We present example results of several key diagnostic features.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Structure Factors for Hot Neutron Matter from Ab Initio Lattice Simulations with High-Fidelity Chiral Interactions

We present the first ab initio lattice calculations of spin and density correlations in hot neutron matter using high-fidelity interactions at next-to-next-to-next-to-leading order in chiral effective field theory. These correlations have a large impact on neutrino heating and shock revival in core-collapse supernovae and are encapsulated in functions called structure factors. Unfortunately, calculations of structure factors using high-fidelity chiral interactions were well out of reach using existing computational methods. In this Letter, we solve the problem using a computational approach called the rank-one operator (RO) method. The RO method is a general technique with broad applications to simulations of fermionic many-body systems. It solves the problem of exponential scaling of computational effort when using perturbation theory for higher-body operators and higher-order corrections. Using the RO method, we compute the vector and axial static structure factors for hot neutron matter as a function of temperature and density. Here, the ab initio lattice results are in good agreement with virial expansion calculations at low densities but are more reliable at higher densities. Random phase approximation codes used to estimate neutrino opacity in core-collapse supernovae simulations can now be calibrated with ab initio lattice calculations.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Transient Photocurrent From High-Voltage Vertical GaN Diodes Irradiated With Electrons: Experiments and Simulations

Radiation-hard high-voltage vertical GaN p-n diodes are being developed for use in power electronics subjected to ionizing radiation. Here, we present a comparison of the measured and simulated photocurrent response of diodes exposed to ionizing irradiation with 70 keV and 20 MeV electrons at dose rates in the range of 1.4x10 7 - 5.0x10 8 rad(GaN)/s. The simulations correctly predict the trend in measured steady-state photocurrent and agree with experimental results within a factor of 2. Furthermore, simulations of the transient photocurrent response to dose rates with uniform and non-uniform ionization depth profiles uncover the physical processes involved that cannot be otherwise experimentally observed due to orders of magnitude larger RC time constant of the test circuit. The simulations were performed using an Exploratory Physics Development code developed at Sandia National Laboratories. The code offers the capability to include defect physics under more general conditions, not included in commercially available software packages, extending the applicability of the simulations to different types of radiation environments.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Data for L-Malic Acid Production from Xylose by Engineered Saccharomyces cerevisiae

L-malic acid is widely used in the food, chemical, and pharmaceutical industries. Here, we report on production of malic acid from xylose, the second most abundant sugar in lignocellulosic hydrolysates, by engineered Saccharomyces cerevisiae . To enable malic acid production in a xylose-assimilating S. cerevisiae , we overexpressed PYC1 and PYC2, coding for pyruvate carboxylases, a truncated MDH3 coding for malate dehydrogenase, and SpMAE1, coding for a Schizosaccharomyces pombe malate transporter. Additionally, both the ethanol- and glycerol-producing pathways were blocked to enhance malic acid production. The resulting strain produced malic acid from both glucose and xylose, but it produced much higher titers of malic acid from xylose than glucose. Interestingly, the engineered strain had higher malic acid yield from lower concentrations (10 g L‒1) of xylose, with no ethanol production, than from higher xylose concentrations (20 and 40 g L‒1). As such, a fed-batch culture maintaining xylose concentrations at low levels was conducted and 61.2 g L‒1 of malic acid was produced, with a productivity of 0.32 g L‒1 h. These results represent successful engineering of S. cerevisiae for the production of malic acid from xylose, confirming that that xylose offers the efficient production of various biofuels and chemicals by engineered S. cerevisiae .

Conversion↗

CLimate Impact: Determining Etiology thRough pAthways (CLDERA)

Climate impacts have broad economic, health, political, and national security ramifications. Societally relevant impacts are typically farther downstream, are the product of multiple interacting processes, and can arise over small regions and timeframes because their sources are short-term and localized. Short-term forcings (as can be seen in volcanic eruptions, climatic tipping points (e.g., the collapse of rainforests or the disappearance of sea ice), or in increasingly plausible climate interventions) fundamentally possess low signal-to-noise and could benefit from accounting for the multiple conditional processes through which a downstream impact arises. Under the Grand Challenge LDRD CLDERA (CLimate impacts: Discovering Etiology thRough pAthways), we have developed tools to enable downstream impact attribution from geographically and temporally localized source forcings in the climate. CLDERA developed methods that can distinguish how a localized source drives the climate system to respond with particular impacts. The how is embodied in pathways – the spatio-temporally evolving chain of physical processes that connects a source to a series of increasingly distant impacts. Novel analytic methods in pursuit of downstream impact attribution were developed and demonstrated on simulations and observations of the 1991 eruption of Mt. Pinatubo in the Philippines. As described within this report we have • developed stratospheric expertise and aerosol modeling capabilities in E3SM, • created original methods to detect and model pathways from source-to-impact, and • advanced climate attribution through novel methods, cases, and approaches. Further, CLDERA developed a tiered verification process consisting of controlled datasets to prototype, verify, and refine the original method development. CLDERA increased Sandia’s footprint in the climate analytics community and developed new climate collaborations whilst also creating a cadre of climate analysts at Sandia. The products from CLDERA have been extensive with a total of 9 journal articles published, 12 articles submitted and under review, and an additional 8 articles in preparation. We have produced 1750 simulated years and developed 9 code-bases. This report details these accomplishments and serves as a summary of the work completed during the CLDERA Grand Challenge.

54 ENVIRONMENTAL SCIENCES↗

Base pairing, structural and functional insights into N 4 -methylcytidine (m 4 C) and N 4 ,N 4 -dimethylcytidine (m 4 2 C) modified RNA

The N 4 -methylation of cytidine (m 4 C and m 4 2 C) in RNA plays important roles in both bacterial and eukaryotic cells. In this work, we synthesized a series of m 4 C and m 4 2 C modified RNA oligonucleotides, conducted their base pairing and bioactivity studies, and solved three new crystal structures of the RNA duplexes containing these two modifications. Our thermostability and X-ray crystallography studies, together with the molecular dynamic simulation studies, demonstrated that m 4 C retains a regular C:G base pairing pattern in RNA duplex and has a relatively small effect on its base pairing stability and specificity. By contrast, the m 4 2 C modification disrupts the C:G pair and significantly decreases the duplex stability through a conformational shift of native Watson-Crick pair to a wobble-like pattern with the formation of two hydrogen bonds. This double-methylated m 4 2 C also results in the loss of base pairing discrimination between C:G and other mismatched pairs like C:A, C:T and C:C. The biochemical investigation of these two modified residues in the reverse transcription model shows that both mono- or di-methylated cytosine bases could specify the C:T pair and induce the G to T mutation using HIV-1 RT. In the presence of other reverse transcriptases with higher fidelity like AMV-RT, the methylation could either retain the normal nucleotide incorporation or completely inhibit the DNA synthesis. These results indicate the methylation at N 4 -position of cytidine is a molecular mechanism to fine tune base pairing specificity and affect the coding efficiency and fidelity during gene replication.

59 BASIC BIOLOGICAL SCIENCES↗

Experiences in porting mini-applications to OpenACC and OpenMP on heterogeneous systems

This article studies mini-applications—Minisweep, GenASiS , GPP, and FF—that use computational methods commonly encountered in HPC. We have ported these applications to develop OpenACC and OpenMP versions, and evaluated their performance on Titan (Cray XK7 with K20x GPUs), Cori (Cray XC40 with Intel KNL), Summit (IBM AC922 with Volta GPUs), and Cori-GPU (Cray CS-Storm 500NX with Intel Skylake and Volta GPUs). Our goals are for these new ports to be useful to both application and compiler developers, to document and describe the lessons learned and the methodology to create optimized OpenMP and OpenACC versions, and to provide a description of possible migration paths between the two specifications. Cases where specific directives or code patterns result in improved performance for a given architecture are highlighted. Here, we also include discussions of the functionality and maturity of the latest compilers available on the above platforms with respect to OpenACC or OpenMP implementations.

97 MATHEMATICS AND COMPUTING↗

Reaction dynamics of S( 3 P) with 1,3-butadiene and isoprene: crossed-beam scattering, low-temperature flow experiments, and high-level electronic structure calculations

Sulfur atoms serve as key players in diverse chemical processes, from astrochemistry at very low temperature to combustion at high temperature. Building upon our prior findings, showing cyclization to thiophenes following the reaction of ground-state sulfur atoms with dienes, we here extend this investigation to include many additional reaction products, guided by detailed theoretical predictions. The outcomes highlight the complex formation of products during intersystem crossing (ISC) to the singlet surfaces. Here, we employed crossed-beam velocity map imaging and high-level ab initio methods to explore the reaction of S( 3 P) with 1,3-butadiene and isoprene under single-collision conditions and in low-temperature flows. For the butadiene reaction, our experimental results show the formation of thiophene via H 2 loss, a 2H-thiophenyl radical through H loss, and thioketene through ethene loss at a slightly higher collision energy compared to previous observations. Complementary Chirped-Pulse Fourier-Transform mmWave spectroscopy (CP-FTmmW) measurements in a uniform flow confirmed the formation of thioketene in the reaction at 20 K. For the isoprene reaction, we observed analogous products along with the 2H-thiophenyl radical arising from methyl loss and C 3 H 4 S (loss of ethene or H 2 + acetylene). CP-FTmmW detected the formation of thioformaldehyde via loss of 1,3-butadiene, again in the 20 K flow. Coupled-cluster calculations on the pathways found by the automated kinetic workflow code KinBot support these findings and indicate ISC to the singlet surface, leading to the generation of various long-lived intermediates, including 5-membered heterocycles.

Lang, Jinxin↗

Wire, hybrid, and laser-cut X-pinches as Talbot–Lau backlighters for electron density diagnostics

Talbot–Lau x-ray deflectometry (TXD) enables refraction-based imaging for high-energy-density physics experiments, and thus, it has been studied and developed with the goal of diagnosing plasmas relevant to inertial confinement and magnetic liner inertial fusion. X-pinches, known for reliably generating fast (~1 ns), small (~1 µm) x-ray sources, were driven on the compact current driver generator for ablation structure and implosion studies (~200 kA, 150 ns) as a potential backlighter source for TXD. Considering that different X-pinch configurations have characteristic advantages and drawbacks as x-ray generating loads, three distinct copper X-pinch configurations were studied: the wire X-pinch, the hybrid X-pinch, and the laser-cut X-pinch. Furthermore, the Cu K-shell emission from each configuration was characterized and analyzed regarding the specific backlighter requirements for an 8 keV TXD system: spatial and temporal resolution, number of sources, time of emission, spectrum, and reproducibility. Recommendations for future experimental improvements and applications are presented. The electron density of static objects was retrieved from Moiré images obtained through TXD. This allowed to calculate the mass density of static samples within 4% of the expected value for laser-cut X-pinches, which were found to be the optimal X-pinch configuration for TXD due to their high reproducibility, small source size (≤5 µm), short duration (~1 ns), and up to 106 W peak power near 8 keV photon energy. Plasma loads were imaged through TXD for the first-time using laser-cut X-pinch backlighting. Experimental images were compared with simulations from the x-ray wave-front propagation code, demonstrating that TXD can be a powerful x-ray refraction-based diagnostic for dense Z-pinch loads. Future plans for Talbot–Lau interferometry diagnostics in the pulsed-power environment are described.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Spatial noise correlations in a Si/SiGe two-qubit device from Bell state coherences

Here, we study spatial noise correlations in a Si/SiGe two-qubit device with integrated micromagnets. Our method relies on the concept of decoherence-free subspaces, whereby we measure the coherence time for two different Bell states, designed to be sensitive only to either correlated or anticorrelated noise, respectively. From these measurements we find weak correlations in low-frequency noise acting on the two qubits, while no correlations could be detected in high-frequency noise. We expect nuclear spin noise to have an uncorrelated nature. A theoretical model and numerical simulations give further insight into the additive effect of multiple independent (anti)correlated noise sources with an asymmetric effect on the two qubits as can result from charge noise. Such a scenario in combination with nuclear spins is plausible given the data and the known decoherence mechanisms. This work is highly relevant for the design of optimized quantum error correction codes for spin qubits in quantum dot arrays, as well as for optimizing the design of future quantum dot arrays.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Genome-Wide Discovery of G-Quadruplexes in Wheat: Distribution and Putative Functional Roles

G-quadruplexes are nucleic acid secondary structures formed by a stack of square planar G-quartets. G-quadruplexes were implicated in many biological functions including telomere maintenance, replication, transcription, and translation, in many species including humans and plants. For wheat, however, though it is one of the world’s most important staple food, no G-quadruplex studies have been reported to date. Here, we computationally identify putative G4 structures (G4s) in wheat genome for the first time and compare its distribution across the genome against five other genomes (human, maize, Arabidopsis, rice, and sorghum). We identified close to 1 million G4 motifs with a density of 76 G4s/Mb across the whole genome and 93 G4s/Mb over genic regions. Remarkably, G4s were enriched around three regions, two located on the antisense and one on the sense strand at the following positions: 1) the transcription start site (TSS) (antisense), 2) the first coding domain sequence (CDS) (antisense), and 3) the start codon (sense). Functional enrichment analysis revealed that the gene models containing G4 motifs within these peaks were associated with specific gene ontology (GO) terms, such as developmental process, localization, and cellular component organization or biogenesis. We investigated genes encoding MADS-box transcription factors and showed examples of G4 motifs within critical regulatory regions in the VRN-1 genes in wheat. Furthermore, comparison with other plants showed that monocots share a similar distribution of G4s, but Arabidopsis shows a unique G4 distribution. Our study shows for the first time the prevalence and possible functional roles of G4s in wheat.

59 BASIC BIOLOGICAL SCIENCES↗

Experimental observation of the geodesic acoustic frequency limit for the NBI-driven Alfvén eigenmodes in TJ-II

We study Alfvén Eigenmodes (AEs) in the TJ-II heliac in hydrogen plasmas heated by hydrogen cofield NBI. Taking advantage of the unique TJ-II flexibility in varying plasma current, we have observed strong variation of the AE frequency from f AE ~ 30 to ~ 220 kHz for selected modes. An advanced heavy ion beam probe diagnostic determines the spatial location and internal amplitudes of the modes. The modes satisfy a local AE dispersion relation including the geodesic acoustic frequency that represents the lowest frequency of the mode. Linear MHD-modeling with STELLGAP and FAR3D codes shows that the calculated temporal evolution of the mode frequency reproduces the observed maxima and minima at the same time intervals with a similar frequency range and the radial profile peaks near the outer edge of the observed one.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Modeling fast ion losses due to tearing and internal kink perturbations in MAST-U

Fast ion (FI) loss properties in the presence of tearing mode and internal kink perturbations are numerically investigated for discharges in the MAST-U spherical tokamak, utilizing the MARS-F magnetohydrodynamic stability code and the REORBIT test particle guiding-center orbit-following module. Here, tracing about 100 000 particle markers sampled from the equilibrium distribution of the neutral-beam injection induced FIs, it is found that about 10% out of the total strike the limiting surface (including the divertor surface) in MAST-U discharge 46943, assuming a maximum perturbation of 100 G inside the plasma (corresponding to ~6 G at the Mirnov probe location at the outboard mid-plane). Detailed particle tracing, assuming a uniform initial distribution in the 2D phase space (at given radial locations), reveals that initially counter-current FIs launched near the plasma edge are subject to significant prompt losses, while almost all initially co-current ions remain well confined at the assumed perturbation level. Most lost FIs strike the lower-half of the limiting surface. Finite gyro-radius effects prevent lost ions from striking the top-outer corner of the super-X divertor chamber. A scan of the perturbation level (based on discharge 45163) reveals, not surprisingly, an approximately linear scaling of the particle loss fraction (for counter-current FIs) with respect to the perturbation amplitude.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Large Eddy Simulation of Gasoline Sprays in a Lagrangian–Eulerian Framework Using the High-Order Spectral Element Method

Predicting the spray evolution using simulations requires accurate modeling of the turbulent gas-phase flow field. Here, in this study, the high-order spectral-element method (SEM), implemented in the code Nek5000, was used to provide highly resolved solutions to the turbulent flow field. Spray modeling capabilities were implemented into the Nek5000 code. The spray is modeled in a Lagrangian–Eulerian (LE) framework, where the liquid is represented by discrete parcels of droplets. The method for coupling liquid and gas in the context of SEM is described, which allows for very fine meshes to be used without affecting the stability of the solution. Large-eddy simulations (LES) of the eight-hole ECN Spray G gasoline injector were conducted. Numerical results are compared against experimental data for liquid penetration, droplet size and gas velocity. The morphology of the multiplume spray is compared against experimental data. The effect of different spray injection inputs is analyzed. It was found that using a plume direction of 33 deg and an injection cone angle of 30 deg produced the best results overall. This work shows the applicability of SEM for spray modeling applications, where use of a high-order flow solver can help us understand the multiplume spray aerodynamics and how it leads to plume collapse under certain conditions. Results also highlight the need for tuning spray input parameters in the LE framework, even when high-fidelity gas flow solutions are possible.

33 ADVANCED PROPULSION SYSTEMS↗

Correction for Thompson et al., “Fatty Acid and Alcohol Metabolism in Pseudomonas putida : Functional Analysis Using Random Barcode Transposon Sequencing”

Volume 86, no. 21, 2020, e01665-20, https://doi.org/10.1128/AEM.01665-20. Readers should note that when the authors created the deletion mutant of PP_2675, they deleted the entire region between the gene’s start and stop codons. However, this also deleted the DNA that codes for the first 14 amino acids of the overlapping ORF PP_2676. Additionally, the originally published URL for the JBEI public strain repository was incorrect. The correct link to all strains and plasmids in this study is https://public-registry.jbei .org/folders/641.

59 BASIC BIOLOGICAL SCIENCES↗

U.S. Effort Support to Examinations at Fukushima - Meeting Notes with Updated Information Requests (FY2020)

Much is still not known about the end-state of core materials in each unit that was operating on March 11, 2011 at the Fukushima Daiichi Nuclear Power Station (Daiichi). Information obtained from Daiichi is required to inform Decontamination and Decommissioning (D&D) activities, improving the ability of the Tokyo Electric Power Company Holdings, Incorporated (TEPCO Holdings) to characterize potential hazards and to ensure the safety of workers involved with cleanup activities. This document, which has been updated to include Fiscal Year 2020 (FY2020) information, summarizes results from a U.S. effort to review Daiichi information and extract insights to enhance the safety of existing and future nuclear power plant designs. This U.S. effort, which was initiated in 2014 by the Department of Energy Office of Nuclear Energy (DOE-NE), is completed by a group of experts in reactor safety and plant operations that identify examination needs and evaluate recent Daiichi examination data to address these needs. Since its inception, comprehensive annual reports were issued that document significant safety insights being obtained in areas of special emphasis: system and component performance, radionuclide surveys and sampling, debris end-state location, combustible gas effects, and plant operations and maintenance. In addition to reducing uncertainties related to severe accident modeling progression, these insights have and continue to be used to update guidance for severe accident prevention, mitigation, and emergency planning. Reduced uncertainties in modeling the events at Daiichi improve the realism of reactor safety evaluations that inform future D&D activities. For FY2020, it was decided that the program would gain more benefit from a more concise report that emphasizes new information and insights that affect prior findings and recommendations from the U.S. experts participating in this effort. A key aspect of prior U.S. efforts, the updated list of information requests, is included in this letter report to ensure that they are transmitted to organizations within Japan. In addition, findings and associated recommendations are provided regarding information presented by TEPCO Holdings, Nuclear Damage Compensation and Decommissioning Facilitation Corporation (NDF), and the Japan Atomic Energy Agency (JAEA). This letter report also continues to emphasize how information obtained from the affected reactors at Daiichi has been and will continue to be used to update severe accident management strategies, improve maintenance activities (especially in areas of radiation protection) and reduce uncertainties in systems analysis code models. In addition, recommendations are included that would expand the use of this information to provide insights regarding maintenance, radiation protection, design, and siting activities of existing and new reactors.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations

Background: Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022. Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1–4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models’ predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models’ forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models’ past predictive performance. Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models’ forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models’ forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models’ forecasts of deaths (N=763 predictions from 20 models). Across a 1–4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models. Conclusions: Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks. Funding: AA, BH, BL, LWa, MMa, PP, SV funded by National Institutes of Health (NIH) Grant 1R01GM109718, NSF BIG DATA Grant IIS-1633028, NSF Grant No.: OAC-1916805, NSF Expeditions in Computing Grant CCF-1918656, CCF-1917819, NSF RAPID CNS-2028004, NSF RAPID OAC-2027541, US Centers for Disease Control and Prevention 75D30119C05935, a grant from Google, University of Virginia Strategic Investment Fund award number SIF160, Defense Threat Reduction Agency (DTRA) under Contract No. HDTRA1-19-D-0007, and respectively Virginia Dept of Health Grant VDH-21-501-0141, VDH-21-501-0143, VDH-21-501-0147, VDH-21-501-0145, VDH-21-501-0146, VDH-21-501-0142, VDH-21-501-0148. AF, AMa, GL funded by SMIGE - Modelli statistici inferenziali per governare l'epidemia, FISR 2020-Covid-19 I Fase, FISR2020IP-00156, Codice Progetto: PRJ-0695. AM, BK, FD, FR, JK, JN, JZ, KN, MG, MR, MS, RB funded by Ministry of Science and Higher Education of Poland with grant 28/WFSN/2021 to the University of Warsaw. BRe, CPe, JLAz funded by Ministerio de Sanidad/ISCIII. BT, PG funded by PERISCOPE European H2020 project, contract number 101016233. CP, DL, EA, MC, SA funded by European Commission - Directorate-General for Communications Networks, Content and Technology through the contract LC-01485746, and Ministerio de Ciencia, Innovacion y Universidades and FEDER, with the project PGC2018-095456-B-I00. DE., MGu funded by Spanish Ministry of Health / REACT-UE (FEDER). DO, GF, IMi, LC funded by Laboratory Directed Research and Development program of Los Alamos National Laboratory (LANL) under project number 20200700ER. DS, ELR, GG, NGR, NW, YW funded by National Institutes of General Medical Sciences (R35GM119582; the content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the National Institutes of Health). FB, FP funded by InPresa, Lombardy Region, Italy. HG, KS funded by European Centre for Disease Prevention and Control. IV funded by Agencia de Qualitat i Avaluacio Sanitaries de Catalunya (AQuAS) through contract 2021-021OE. JDe, SMo, VP funded by Netzwerk Universitatsmedizin (NUM) project egePan (01KX2021). JPB, SH, TH funded by Federal Ministry of Education and Research (BMBF; grant 05M18SIA). KH, MSc, YKh funded by Project SaxoCOV, funded by the German Free State of Saxony. Presentation of data, model results and simulations also funded by the NFDI4Health Task Force COVID-19 ( https://www.nfdi4health.de/task-force-covid-19-2 ) within the framework of a DFG-project (LO-342/17-1). LP, VE funded by Mathematical and Statistical modelling project (MUNI/A/1615/2020), Online platform for real-time monitoring, analysis and management of epidemic situations (MUNI/11/02202001/2020); VE also supported by RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), the CETOCOEN EXCELLENCE (CZ.02.1.01/0.0/0.0/17-043/0009632), RECETOX RI project (CZ.02.1.01/0.0/0.0/16-013/0001761). NIB funded by Health Protection Research Unit (grant code NIHR200908). SAb, SF funded by Wellcome Trust (210758/Z/18/Z).

60 APPLIED LIFE SCIENCES↗