What model does MuZero learn?

Model-based reinforcement learning has drawn considerable interest in recent years, given its promise to improve sample efficiency. Moreover, when using deep-learned models, it is potentially possible to learn compact models from complex sensor data. However, the effectiveness of these learned models, particularly their capacity to plan, i.e., to improve the current policy, remains unclear. In this work, we study MuZero, a well-known deep model-based reinforcement learning algorithm, and explore how far it achieves its learning objective of a value-equivalent model and how useful the learned models are for policy improvement. Amongst various other insights, we conclude that the model learned by MuZero cannot effectively generalize to evaluate unseen policies, which limits the extent to which we can additionally improve the current policy by planning with the model

Evaluation of the EndoPAT as a Tool to Assess Endothelial Function

Endothelial dysfunction is a potential target for (pharmaceutical) intervention of several systemic pathological conditions. We investigated the feasibility of the EndoPAT to evaluate acute changes in endothelial function with repeated noninvasive measurements and assessed its discriminating power in different populations. Endothelial function was stable over a longer period of time in renally impaired patients (coefficient of variation 13%). Endothelial function in renally impaired and type 2 diabetic patients was not decreased compared to healthy volunteers (2.9 ± 1.4 and 1.8 ± 0.3, resp., versus 1.8 ± 0.5, P > 0.05). The EndoPAT did not detect an effect of robust interventions on endothelial function in healthy volunteers (glucose load: change from baseline 0.08 ± 0.50, 95% confidence interval −0.44 to 0.60; smoking: change from baseline 0.49 ± 0.92, 95% confidence interval −0.47 to 1.46). This suggests that at present the EndoPAT might not be suitable to assess (changes in) endothelial function in early-phase clinical pharmacology studies. Endothelial function as measured by the EndoPAT could be physiologically different from endothelial function as measured by conventional techniques. This should be investigated carefully before the EndoPAT can be considered a useful tool in drug development or clinical practice

Multiple common garden experiments suggest lack of local adaptation in an invasive ornamental plant

Aims: Adaptive evolution along geographic gradients of climatic conditions is suggested to facilitate the spread of invasive plant species, leading to clinal variation among populations in the introduced range. We investigated whether adaptation to climate is also involved in the invasive spread of an ornamental shrub, Buddleja davidii, across western and central Europe. Material and Methods: We combined a common garden experiment, replicated in three climatically different central European regions, with reciprocal transplantation to quantify genetic differentiation in growth and reproductive traits of 20 invasive B. davidii populations. Additionally, we compared compensatory regrowth among populations after clipping of stems to simulate mechanical damage. Important findings: Our results do not provide evidence for clinal variation among invasive B. davidii populations: populations responded similarly to the different environments, and trait values were not correlated to climatic conditions or geographic coordinates of their home sites. Moreover, we did not detect differences in the compensatory ability of populations. We suppose that the invasive spread of B. davidii has been facilitated by phenotypic plasticity rather than by adaptation to climate, and that continent-wide shuffling of cultivars due to horticultural trade may have limited local adaptation so far

Critical assessment of human metabolic pathway databases: a stepping stone for future integration

<p>Abstract</p> <p>Background</p> <p>Multiple pathway databases are available that describe the human metabolic network and have proven their usefulness in many applications, ranging from the analysis and interpretation of high-throughput data to their use as a reference repository. However, so far the various human metabolic networks described by these databases have not been systematically compared and contrasted, nor has the extent to which they differ been quantified. For a researcher using these databases for particular analyses of human metabolism, it is crucial to know the extent of the differences in content and their underlying causes. Moreover, the outcomes of such a comparison are important for ongoing integration efforts.</p> <p>Results</p> <p>We compared the genes, EC numbers and reactions of five frequently used human metabolic pathway databases. The overlap is surprisingly low, especially on reaction level, where the databases agree on 3% of the 6968 reactions they have combined. Even for the well-established tricarboxylic acid cycle the databases agree on only 5 out of the 30 reactions in total. We identified the main causes for the lack of overlap. Importantly, the databases are partly complementary. Other explanations include the number of steps a conversion is described in and the number of possible alternative substrates listed. Missing metabolite identifiers and ambiguous names for metabolites also affect the comparison.</p> <p>Conclusions</p> <p>Our results show that each of the five networks compared provides us with a valuable piece of the puzzle of the complete reconstruction of the human metabolic network. To enable integration of the networks, next to a need for standardizing the metabolite names and identifiers, the conceptual differences between the databases should be resolved. Considerable manual intervention is required to reach the ultimate goal of a unified and biologically accurate model for studying the systems biology of human metabolism. Our comparison provides a stepping stone for such an endeavor.</p

The role of the g9/2 orbital in the development of collectivity in the A = 60 region: The case of 61Co

An extensive study of the level structure of 61Co has been performed following the complex 26Mg(48Ca, 2a4npg)61Co reaction at beam energies of 275, 290 and 320 MeV using Gammasphere and the Fragment Mass Analyzer (FMA). The low-spin structure is discussed within the framework of shell-model calculations using the GXPF1A effective interaction. Two quasi-rotational bands consisting of stretched-E2 transitions have been established up to spins I = 41/2 and (43/2), and excitation energies of 17 and 20 MeV, respectively. These are interpreted as signature partners built on a neutron {\nu}(g9/2)2 configuration coupled to a proton {\pi}p3/2 state, based on Cranked Shell Model (CSM) calculations and comparisons with observations in neighboring nuclei. In addition, four I = 1 bands were populated to high spin, with the yrast dipole band interpreted as a possible candidate for the shears mechanism, a process seldom observed thus far in this mass region

Characterizing the kinetics of presepsin and associated inflammatory biomarkers in human endotoxemia

In this study, we describe the kinetics of a new potential inflammatory biomarker, presepsin, together with a panel of well-established biomarkers in a human endotoxemia study. We evaluated biomarker correlations and identified combinations that could hold valuable insights regarding the state of infection.Pharmacolog

Understanding cation trends for hydrogen evolution on platinum and gold electrodes in alkaline media

In this work, we study how the cation identity and concentration alter the kinetics of the hydrogen evolution reaction (HER) on platinum and gold electrodes. A previous work suggested an inverted activity trend as a function of alkali metal cation when comparing the performance of platinum and gold catalysts in alkaline media. We show that weakly hydrated cations (K+) favor HER on gold only at low overpotentials (or lower alkalinity), whereas in more alkaline pH (or high overpotentials), a higher activity is observed using electrolytes containing strongly hydrated cations (Li+). We find a similar trend for platinum; however, the inhibition of HER by weakly hydrated cations on platinum is observed already at lower alkalinity and lower cation concentrations, suggesting that platinum interacts more strongly with metal cations than gold. We propose that weakly hydrated cations stabilize the transition state of the water dissociation step more favorably due to their higher near-surface concentration in comparison to a strongly hydrated cation such as Li+. However, at high pH and consequently higher near-surface cation concentrations, the accumulation of these species at the outer Helmholtz plane inhibits HER. This is especially pronounced on platinum, where a change in the rate-determining step is observed at pH 13 when using a Li+- or K+-containing electrolyte.Horizon 2020(H2020)722614-ELCORELCatalysis and Surface Chemistr

Nur77-deficiency in bone marrow-derived macrophages modulates inflammatory responses, extracellular matrix homeostasis, phagocytosis and tolerance

The nuclear orphan receptor Nur77 (NR4A1, TR3, or NGFI-B) has been shown to modulate the inflammatory response of macrophages. To further elucidate the role of Nur77 in macrophage physiology, we compared the transcriptome of bone marrow-derived macrophages (BMM) from wild-type (WT) and Nur77-knockout (KO) mice. In line with previous observations, SDF-1α (CXCL12) was among the most upregulated genes in Nur77-deficient BMM and we demonstrated that Nur77 binds directly to the SDF-1α promoter, resulting in inhibition of SDF-1α expression. The cytokine receptor CX3CR1 was strongly downregulated in Nur77-KO BMM, implying involvement of Nur77 in macrophage tolerance. Ingenuity pathway analyses (IPA) to identify canonical pathways regulation and gene set enrichment analyses (GSEA) revealed a potential role for Nur77 in extracellular matrix homeostasis. Nur77-deficiency increased the collagen content of macrophage extracellular matrix through enhanced expression of several collagen subtypes and diminished matrix metalloproteinase (MMP)-9 activity. IPA upstream regulator analyses discerned the small GTPase Rac1 as a novel regulator of Nur77-mediated gene expression. We identified an inhibitory feedback loop with increased Rac1 activity in Nur77-KO BMM, which may explain the augmented phagocytic activity of these cells. Finally, we predict multiple chronic inflammatory diseases to be influenced by macrophage Nur77 expression. GSEA and IPA associated Nur77 to osteoarthritis, chronic obstructive pulmonary disease, rheumatoid arthritis, psoriasis, and allergic airway inflammatory diseases. Altogether these data identify Nur77 as a modulator of macrophage function and an interesting target to treat chronic inflammatory diseas