YAHPO Gym -- An Efficient Multi-Objective Multi-Fidelity Benchmark for Hyperparameter Optimization

When developing and analyzing new hyperparameter optimization methods, it is vital to empirically evaluate and compare them on well-curated benchmark suites. In this work, we propose a new set of challenging and relevant benchmark problems motivated by desirable properties and requirements for such benchmarks. Our new surrogate-based benchmark collection consists of 14 scenarios that in total constitute over 700 multi-fidelity hyperparameter optimization problems, which all enable multi-objective hyperparameter optimization. Furthermore, we empirically compare surrogate-based benchmarks to the more widely-used tabular benchmarks, and demonstrate that the latter may produce unfaithful results regarding the performance ranking of HPO methods. We examine and compare our benchmark collection with respect to defined requirements and propose a single-objective as well as a multi-objective benchmark suite on which we compare 7 single-objective and 7 multi-objective optimizers in a benchmark experiment. Our software is available at [https://github.com/slds-lmu/yahpo_gym].Comment: Accepted at the First Conference on Automated Machine Learning (Main Track). 39 pages, 12 tables, 10 figures, 1 listin

Shock motion inside a varying cross-section channel and consequences on the downstream flow

Shock wave propagation in a variable cross-section channel is a recurrent issue in the literature. Seminal work regarding this flow configuration has been proposed by~\citeapos{whitham_propagation_1958} through the derivation of a one-dimensional approach connecting the shock Mach number and the area channel: the A-M relation. It is based on strong theoretical restrictions: (i) shock equations applied on a $C^+$, (ii) omission of the post-shock influence, and (iii) initial conditions at rest. It has been the focus of many studies aimed at generalizing it. However, very little attention has been paid to the study of the shock motion outside the varying cross-sectional region since~\citeapos{russell_shock-wave_2018}. The objective of the current work is to describe and to explain the shock wave behaviour in a constant area channel behind a convergent or divergent channel. It is found that the shock propagation in the downstream uniform area region is influenced by the post-shock flow unsteadinesses. Thence, the Whitham model is not suited to the shock motion study in a constant area region downstream of a convergent or divergent area region. A detailed flow description is provided and a quasi-steady model for determining the waves intensity at large times is proposed. This model gives accurate results without any assumptions on the shock strength, area variation or the shock upstream state. Finally, this study points out the limits of the use of Whitham's theory in a variable area channel with increasing section variation rate (where $|\mathrm{dA/A(x+dx)}| \geq |\mathrm{dA/A(x)}|$)

Pulsed flow turbine design recommendations

A preliminary analysis of turbine design, fit for pulsed flow is proposed in this paper. It focuses on an academic 2D configuration using inviscid flows, since pressure loads due to wave propagation are several order of magnitude higher than friction and viscous effects do not significantly impinge on the inviscid part. As such, a large parametric study is carried out using the design of experiments methodology. A performance indicator adapted to unsteady environment is carefully defined before detailing the factors chosen for the design of experiments. Since the number of factors is substantial, a screening design to identify the factors influence on the output is first established. The non-influential factors were then omitted in a more quantitative study of the output law. The surface response calculation allows to determine the factors level favouring the best output. Consequently, the main trends in the turbine design driven by a pulsed flow can be stated

Implications of the E-selectin S128R mutation for drug discovery

The C-type lectin E-selectin mediates the rolling of circulating leukocytes on vascular endothelial cells during the inflammatory process. In numerous studies, the S128R mutation of the E-selectin was associated with cardiovascular and autoimmune diseases. There is evidence that the S128R E-selectin mutation leads to a loss in ligand specificity, thus increasing leukocyte recruitment. Apart from the natural tetrasaccharide ligand sialyl Lewisx (sLex), it has previously been proposed that non-fucosylated carbohydrates also bind to S128R E-selectin. To evaluate the therapeutic potential of the antagonism of the E-selectin mutant, ligand specificity was reinvestigated on a molecular basis. We determined the ligand specificity of wild-type and S128R E-selectin in a target-based competitive assay, a glycan array screen and cell-based binding assays under static and flow conditions. Regarding ligand-specificity, the binding properties of S128R E-selectin were identical to those of wt E-selectin, i.e., no mutant-specific binding of 3′-sialyl-N-acetyllactosamine, heparin, fetuin and K562 cells was observed. Additionally, the binding affinities of glycomimetic E-selectin antagonists were identical for wt and S128R E-selectin. Overall, the previous reports on carbohydrate ligand promiscuity of S128R E-selectin could not be confirme

E-selectin ligand complexes adopt an extended high-affinity conformation

E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewis(x) (sLe(x)). Efficient leukocyte recruitment under vascular flow conditions depends on an increased lifetime of E-selectin/ligand complexes under tensile force in a so-called catch-bond binding mode. Co-crystal structures of a representative fragment of the extracellular E-selectin region with sLe(x) and a glycomimetic antagonist thereof reveal an extended E-selectin conformation, which is identified as a high-affinity binding state of E-selectin by molecular dynamics simulations. Small-angle X-ray scattering experiments demonstrate a direct link between ligand binding and E-selectin conformational transition under static conditions in solution. This permits tracing a series of concerted structural changes connecting ligand binding to conformational stretching as the structural basis of E-selectin catch-bond-mediated leukocyte recruitment. The detailed molecular view of the binding site paves the way for the design of a new generation of selectin antagonists. This is of special interest, since their therapeutic potential was recently demonstrated with the pan-selectin antagonists GMI-1070 (Rivipansel)

Pulsed Flow Turbine Design Recommendations

A preliminary analysis of turbine design, fit for pulsed flow, is proposed in this paper. It focuses on an academic 2D configuration using inviscid flows, since pressure loads due to wave propagation are several orders of magnitude higher than friction and viscous effects do not significantly impinge on the inviscid part, as previously shown by Hermet, 2021. As such, a large parametric study was carried out using the design of experiments methodology. A performance indicator adapted to unsteady environment is carefully defined before detailing the factors chosen for the design of experiments. Since the number of factors is substantial, a screening design to identify the factors influence on the output is first established. The non-influential factors are then omitted in a more quantitative study of the output law. The surface response calculation allows determining the factor level favouring the best output. Consequently, the main trends in the turbine design driven by a pulsed flow can be stated

Isolation and characterization of new Puumala orthohantavirus strains from Germany

Orthohantaviruses are re-emerging rodent-borne pathogens distributed all over the world. Here, we report the isolation of a Puumala orthohantavirus (PUUV) strain from bank voles caught in a highly endemic region around the city Osnabrück, north-west Germany. Coding and non-coding sequences of all three segments (S, M, and L) were determined from original lung tissue, after isolation and after additional passaging in VeroE6 cells and a bank vole-derived kidney cell line. Different single amino acid substitutions were observed in the RNA-dependent RNA polymerase (RdRP) of the two stable PUUV isolates. The PUUV strain from VeroE6 cells showed a lower titer when propagated on bank vole cells compared to VeroE6 cells. Additionally, glycoprotein precursor (GPC)-derived virus-like particles of a German PUUV sequence allowed the generation of monoclonal antibodies that allowed the reliable detection of the isolated PUUV strain in the immunofluorescence assay. In conclusion, this is the first isolation of a PUUV strain from Central Europe and the generation of glycoprotein-specific monoclonal antibodies for this PUUV isolate. The obtained virus isolate and GPC-specific antibodies are instrumental tools for future reservoir host studies