Where Did the Gap Go? Reassessing the Long-Range Graph Benchmark

The recent Long-Range Graph Benchmark (LRGB, Dwivedi et al. 2022) introduced a set of graph learning tasks strongly dependent on long-range interaction between vertices. Empirical evidence suggests that on these tasks Graph Transformers significantly outperform Message Passing GNNs (MPGNNs). In this paper, we carefully reevaluate multiple MPGNN baselines as well as the Graph Transformer GPS (Ramp\'a\v{s}ek et al. 2022) on LRGB. Through a rigorous empirical analysis, we demonstrate that the reported performance gap is overestimated due to suboptimal hyperparameter choices. It is noteworthy that across multiple datasets the performance gap completely vanishes after basic hyperparameter optimization. In addition, we discuss the impact of lacking feature normalization for LRGB's vision datasets and highlight a spurious implementation of LRGB's link prediction metric. The principal aim of our paper is to establish a higher standard of empirical rigor within the graph machine learning community

Learning the language of QCD jets with transformers

Transformers have become the primary architecture for natural language processing. In this study, we explore their use for auto-regressive density estimation in high-energy jet physics, which involves working with a high-dimensional space. We draw an analogy between sentences and words in natural language and jets and their constituents in high-energy physics. Specifically, we investigate density estimation for light QCD jets and hadronically decaying boosted top jets. Since transformers allow easy sampling from learned densities, we exploit their generative capability to assess the quality of the density estimate. Our results indicate that the generated data samples closely resemble the original data, as evidenced by the excellent agreement of distributions such as particle multiplicity or jet mass. Furthermore, the generated samples are difficult to distinguish from the original data, even by a powerful supervised classifier. Given their exceptional data processing capabilities, transformers could potentially be trained directly on the massive LHC data sets to learn the probability densities in high-energy jet physics.Comment: Few references added; Version accepted for publication by JHE

WL meet VC

Recently, many works studied the expressive power of graph neural networks (GNNs) by linking it to the $1$-dimensional Weisfeiler--Leman algorithm ($1\text{-}\mathsf{WL}$). Here, the $1\text{-}\mathsf{WL}$ is a well-studied heuristic for the graph isomorphism problem, which iteratively colors or partitions a graph's vertex set. While this connection has led to significant advances in understanding and enhancing GNNs' expressive power, it does not provide insights into their generalization performance, i.e., their ability to make meaningful predictions beyond the training set. In this paper, we study GNNs' generalization ability through the lens of Vapnik--Chervonenkis (VC) dimension theory in two settings, focusing on graph-level predictions. First, when no upper bound on the graphs' order is known, we show that the bitlength of GNNs' weights tightly bounds their VC dimension. Further, we derive an upper bound for GNNs' VC dimension using the number of colors produced by the $1\text{-}\mathsf{WL}$. Secondly, when an upper bound on the graphs' order is known, we show a tight connection between the number of graphs distinguishable by the $1\text{-}\mathsf{WL}$ and GNNs' VC dimension. Our empirical study confirms the validity of our theoretical findings.Comment: arXiv admin note: text overlap with arXiv:2206.1116

Diversity and ecology of bacteriocyte-associated symbionts in adelgids (Hemiptera: Adelgidae)

Symbiosen zwischen Insekten und Bakterien sind in der Natur weit verbreitet. Geschätzte 10% aller Insekten beherbergen in ihrer Körperhöhle Bakteriozyten- assoziierte Symbionten. Diese durch direkte Vererbung weitergegebenen Symbionten sind für die Wirtsinsekten oft von essentieller Bedeutung. Sie stellen Nährstoffe zur Verfügung, die in der Wirtsnahrung abwesend sind. Die Adelgiden (Insecta: Hemiptera: Adelgidae) sind eine relativ kleine Insektenfamilie (bestehend aus ~ 65 beschriebene Arten), stellen dennoch schwerwiegende Schädlinge für das Ökosystem Wald dar. Die Adelgiden sind eine Schwesterngruppe der Phloem- saugenden Blattläuse, die als obligaten Symbionten meist Buchnera aphidicola enthalten. Das Wissen über die Bakteriozyten- assoziierten Symbionten der Adelgiden ist immer noch spärlich, aus diesem Grund wird die Adelgiden/Symbionten Symbiose in dieser Dissertationsarbeit untersucht. Adelgiden beherbergen verschiedene vertikal übertragene Bakteriozyten- assoziierte Symbionten, die zu den Gamma- und den Betaproteobakterien gehören. Sie sind weder zu B. aphidicola noch zu anderen Insektensymbionten nah verwandt. Dem zu Folge nahmen die Adelgiden während ihrer evolutionären Entwicklung ihre eigenen Symbionten nach der Trennung von den Blattläusen auf. Basierend auf phylogenetischen Studien und Genomanalysen repräsentieren diese symbiotischen Verbindungen relativ kurzzeitige Gemeinschaften. Sowohl Co-Evolutionsereignisse zwischen Symbionten und Wirtsinsekten, wie auch ein Austausch von Symbionten wurden gezeigt. Diese evolutionären Ereignisse definieren diese Symbiose. Zukünftige Studien über die Diversität von Adelgidensymbionten und ihrer Genome wird ein tieferes Verständnis über diese Symbiose bringen. Diese Insektenfamilie könnte als Fallbeispiel für Symbiontenaustausch und Symbiontenaufnahme in Insekten dienen.Symbioses between bacteria and insects are widespread in nature. Estimated ten percent of all insects harbour bacteriocyte-associated symbionts in their body cavity. These heritable symbionts provide essential nutrients, which are absent in the hosts’ diet; therefore, they are often essential for their host insect. Adelgids (Insecta: Hemiptera: Adelgidae), members of a relatively small insect family (~ 65 described species), contain species that represent severe pests for the forest ecosystem. The adelgids are a sister group of the phloem-feeding aphids, which often harbour one single obligate symbionts called Buchnera aphidicola. Knowledge about adelgids bacteriocyte-associated symbionts is still scarce and thus the adelgid/symbiont association was examined in this thesis. Adelgids harbour various vertically transmitted bacteriocyte-associated symbionts that belong either to Gammaproteobacteria or Betaproteobacteria. Interestingly, none of the newly found symbionts is directly related to B. aphidicola or other symbionts of insects. Based on phylogenetic and genome analyses, these relationships represent relatively recent symbiotic associations. Co-evolution between symbiont and host, and symbiont replacements were identified that define this symbiosis. Hence, adelgids acquired their own symbionts during evolution after the separation from their aphid sister group. Future studies of adelgid symbionts diversity and their genomes will bring a deeper understanding of this symbiosis. The insect family Adelgidae could serve as a case study for symbiont replacement and multiple acquisition events

Differential effects of insulin-like growth factor binding proteins-1, -2, -3, and -6 on cultured growth plate chondrocytes

Differential effects of insulin-like growth factor binding proteins-1, -2, -3, and -6 on cultured growth plate chondrocytes.BackgroundIn children with chronic renal failure (CRF), impairment of longitudinal growth is in part due to excess amounts of circulating high-affinity insulin-like growth factor binding proteins (IGFBPs) that might decrease or prevent insulin-like growth factor (IGF) binding to its signaling receptor. However, it appears from the clinical studies that various IGFBPs may have contrasting effects on longitudinal growth. Because of the potential importance of the IGFBPs as modulators of longitudinal growth in pediatric CRF, the aim of the present study was to investigate the biological effects of IGFBP-1, -2, -3, and -6 on cultured growth plate chondrocytes that express the type 1 IGF receptor.MethodsThe effects of exogenous IGFBPs on IGF-independent and IGF-dependent proliferation of rat growth plate chondrocytes in primary culture were investigated. Proliferation was assessed by colony formation of agarose-stabilized long-term suspension cultures and by the [3H]thymidine assay. The effects of IGFBPs on IGF-I binding and the binding of IGFBPs to chondrocytes were assessed by binding studies with radiolabeled proteins in monolayer culture.ResultsIntact IGFBP-1, IGFBP-2 and IGFBP-6 inhibited in equimolar concentration the IGF-I- and IGF-II-stimulated DNA synthesis and cell proliferation, whereas the biological activity of IGFBP-3 was complex. It had an IGF-independent antiproliferative effect and also inhibited IGF-dependent chondrocyte proliferation under coincubation conditions, whereas under preincubation conditions IGFBP-3 enhanced IGF-I-responsiveness. Studies on the mechanism by which IGFBP-3 potentiated IGF activity demonstrated that under preincubation conditions IGFBP-3 is capable to associate with the cell membrane and to facilitate IGF-I cell surface binding.ConclusionsIntact IGFBP-1, IGFBP-2 and IGFBP-6 act exclusively as growth inhibitors on IGF-dependent proliferation of growth plate chondrocytes. IGFBP-3, however, can either inhibit IGF-independent and IGF-dependent cell proliferation, or enhance IGF responsiveness of chondrocytes dependent on the temporal relationship to the IGF exposure

CXCR-4 expression by circulating endothelial progenitor cells and SDF-1 serum levels are elevated in septic patients

Background: Endothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival. In this study, we investigated, whether surface expression of chemokine receptors and other receptors important for EPC homing is upregulated by EPC from septic patients and if this is associated with clinical outcome. Methods: Peripheral blood mononuclear cells from septic patients (n = 30), ICU control patients (n = 11) and healthy volunteers (n = 15) were isolated by Ficoll density gradient centrifugation. FACS-analysis was used to measure the expression of the CXC motif chemokine receptors (CXCR)-2 and − 4, the receptor for advanced glycation endproducts (RAGE) and the stem cell factor receptor c-Kit. Disease severity was assessed via the Simplified Acute Physiology Score (SAPS) II. The serum concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor (SDF)-1α and angiopoietin (Ang)-2 were determined with Enzyme linked Immunosorbent Assays. Results: EPC from septic patients expressed significantly more CXCR-4, c-Kit and RAGE compared to controls and were associated with survival-probability. Significantly higher serum concentrations of VEGF, SDF-1α and Ang-2 were found in septic patients. SDF-1α showed a significant association with survival. Conclusions: Our data suggest that SDF-1α and CXCR-4 signaling could play a crucial role in EPC homing in the course of sepsis

CXCR-4 expression by circulating endothelial progenitor cells and SDF-1 serum levels are elevated in septic patients

Background: Endothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival. In this study, we investigated, whether surface expression of chemokine receptors and other receptors important for EPC homing is upregulated by EPC from septic patients and if this is associated with clinical outcome. Methods: Peripheral blood mononuclear cells from septic patients (n = 30), ICU control patients (n = 11) and healthy volunteers (n = 15) were isolated by Ficoll density gradient centrifugation. FACS-analysis was used to measure the expression of the CXC motif chemokine receptors (CXCR)-2 and − 4, the receptor for advanced glycation endproducts (RAGE) and the stem cell factor receptor c-Kit. Disease severity was assessed via the Simplified Acute Physiology Score (SAPS) II. The serum concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor (SDF)-1α and angiopoietin (Ang)-2 were determined with Enzyme linked Immunosorbent Assays. Results: EPC from septic patients expressed significantly more CXCR-4, c-Kit and RAGE compared to controls and were associated with survival-probability. Significantly higher serum concentrations of VEGF, SDF-1α and Ang-2 were found in septic patients. SDF-1α showed a significant association with survival. Conclusions: Our data suggest that SDF-1α and CXCR-4 signaling could play a crucial role in EPC homing in the course of sepsis

Urinary NMR Profiling in Pediatric Acute Kidney Injury—A Pilot Study

Acute kidney injury (AKI) in critically ill children and adults is associated with significant short- and long-term morbidity and mortality. As serum creatinine- and urine output-based definitions of AKI have relevant limitations, there is a persistent need for better diagnostics of AKI. Nuclear magnetic resonance (NMR) spectroscopy allows for analysis of metabolic profiles without extensive sample manipulations. In the study reported here, we examined the diagnostic accuracy of NMR urine metabolite patterns for the diagnosis of neonatal and pediatric AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. A cohort of 65 neonatal and pediatric patients (0–18 years) with established AKI of heterogeneous etiology was compared to both a group of apparently healthy children (n = 53) and a group of critically ill children without AKI (n = 31). Multivariate analysis identified a panel of four metabolites that allowed diagnosis of AKI with an area under the receiver operating characteristics curve (AUC-ROC) of 0.95 (95% confidence interval 0.86–1.00). Especially urinary citrate levels were significantly reduced whereas leucine and valine levels were elevated. Metabolomic differentiation of AKI causes appeared promising but these results need to be validated in larger studies. In conclusion, this study shows that NMR spectroscopy yields high diagnostic accuracy for AKI in pediatric patients

Population pharmacokinetics of mycophenolic acid in pediatric renal transplant patients using parametric and nonparametric approaches.

International audienceMycophenolic acid (MPA) is an immunosuppressive drug widely used in the prevention of acute rejection in pediatric renal transplant recipients and is characterized by a wide inter-individual variability in its pharmacokinetics. The aim of this study was to compare population pharmacokinetic modeling of MPA in pediatric renal transplant recipients given mycophenolate mofetil, the ester prodrug of MPA, using parametric and nonparametric population methods. The data from 34 pediatric renal transplants (73 full pharmacokinetic profiles obtained on day 21, months 3, 6 and 9 post-transplant) were analyzed using both the nonlinear mixed-effect modeling (NONMEM) and nonparametric adaptive grid (NPAG) approaches, based on a two-compartment model with first order lagged time absorption and first order elimination. The predictive performance of the two models was evaluated in a separate group of 32 patients. Higher mean population parameter values and ranges of individual pharmacokinetic parameters were obtained with NPAG, especially for the elimination constant ke: mean 1.16 h(-1) (0.26-4.33 h(-1)) and 0.78 h(-1) (0.66-1.15 h(-1)) with NPAG and NONMEM, respectively. With NPAG, the skewness and kurtosis values for ke (2.03 and 7.80, respectively) were far from the theoretical values expected for normal distributions. Such a non-normal distribution could explain the high value of shrinkage (35%) obtained for this parameter with the parametric NONMEM method. Bayesian forecasting of mycophenolic acid exposure using the NPAG population pharmacokinetic parameters as priors yielded a better predictive performance, with a significantly smaller bias than with the NONMEM model (-1.68% vs -9.53%, p<0.0001). In conclusion, in the present study, NPAG was found to be the most adequate population pharmacokinetic method to describe the pharmacokinetics of MPA in pediatric renal transplant recipients