Bridging Graph Position Encodings for Transformers with Weighted Graph-Walking Automata

A current goal in the graph neural network literature is to enable transformers to operate on graph-structured data, given their success on language and vision tasks. Since the transformer's original sinusoidal positional encodings (PEs) are not applicable to graphs, recent work has focused on developing graph PEs, rooted in spectral graph theory or various spatial features of a graph. In this work, we introduce a new graph PE, Graph Automaton PE (GAPE), based on weighted graph-walking automata (a novel extension of graph-walking automata). We compare the performance of GAPE with other PE schemes on both machine translation and graph-structured tasks, and we show that it generalizes several other PEs. An additional contribution of this study is a theoretical and controlled experimental comparison of many recent PEs in graph transformers, independent of the use of edge features.Comment: Camera-ready version, reduced certain claims and minor rewordin

Oncometabolites:linking altered metabolism with cancer

The discovery of cancer-associated mutations in genes encoding key metabolic enzymes has provided a direct link between altered metabolism and cancer. Advances in mass spectrometry and nuclear magnetic resonance technologies have facilitated high-resolution metabolite profiling of cells and tumors and identified the accumulation of metabolites associated with specific gene defects. Here we review the potential roles of such "oncometabolites" in tumor evolution and as clinical biomarkers for the detection of cancers characterized by metabolic dysregulation

The emerging role of fumarate as an oncometabolite

The drive to understand how altered cellular metabolism and cancer are linked has caused a paradigm shift in the focus of cancer research. The discovery of a mutated metabolic enzyme, isocitrate dehydrogenase 1 (IDH1), that leads to accumulation of the oncometabolite 2-hydroxyglutarate, provided significant direct evidence that dysfunctional metabolism plays an important role in oncogenesis. Striking parallels exist with the Krebs cycle enzyme fumarate hydratase (FH), a tumour suppressor, whose mutation is associated with the development of leiomyomata, renal cysts, and tumours. Loss of FH enzymatic activity results in accumulation of intracellular fumarate which has been proposed to act as a competitive inhibitor of 2-oxoglutarate-dependent oxygenases including the hypoxia-inducible factor (HIF) hydroxylases, thus activating oncogenic HIF pathways. Interestingly, our studies have questioned the role of HIF and have highlighted other candidate mechanisms, in particular the non-enzymatic modification of cysteine residues (succination) that could lead to disruption or loss of protein functions, dysfunctional cell metabolism and cell signalling. Here we discuss the evidence for proposing fumarate as an oncometabolite

An HPC-Based Hydrothermal Finite Element Simulator for Modeling Underground Response to Community-Scale Geothermal Energy Production

Geothermal heat, as renewable energy, shows great advantage with respect to its environmental impact due to its significantly lower CO2 emissions than conventional fossil fuel. Open and closed-loop geothermal heat pumps, which utilize shallow geothermal systems, are an efficient technology for cooling and heating buildings, especially in urban areas. Integrated use of geothermal energy technologies for district heating, cooling, and thermal energy storage can be applied to optimize the subsurface for communities to provide them with multiple sustainable energy and community resilience benefits. The utilization of the subsurface resources may lead to a variation in the underground environment, which might further impact local environmental conditions. However, very few simulators can handle such a highly complex set of coupled computations on a regional or city scale. We have developed high-performance computing (HPC) based hydrothermal finite element (FE) simulator that can simulate the subsurface and its hydrothermal conditions at a scale of tens of km. The HPC simulator enables us to investigate the subsurface thermal and hydrologic response to the built underground environment (such as basements and subways) at the community scale. In this study, a coupled hydrothermal simulator is developed based on the open-source finite element library deal.II. The HPC simulator was validated by comparing the results of a benchmark case study against COMSOL Multiphysics, in which Aquifer Thermal Energy Storage (ATES) is modeled and a process of heat injection into ATES is simulated. The use of an energy pile system at the Treasure Island redevelopment site (San Francisco, CA, USA) was selected as a case study to demonstrate the HPC capability of the developed simulator. The simulator is capable of modeling multiple city-scale geothermal scenarios in a reasonable amount of time.Comment: 46th Workshop on Geothermal Reservoir Engineering Stanford University, Stanford, California, February 15-17, 202

Expression of <i>Idh1</i>^R132H in the murine subventricular zone stem cell niche recapitulates features of early gliomagenesis

Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1(R132H) in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced α-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1(R132H) mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis

Birds in the playground: Evaluating the effectiveness of an urban environmental education project in enhancing school children's awareness, knowledge and attitudes towards local wildlife.

Children nowadays, particularly in urban areas, are more disconnected from nature than ever before, leading to a large-scale "extinction of experience" with the natural world. Yet there are many potential benefits from children interacting with nature first-hand, including via outdoor learning opportunities. Urban environmental education programmes typically aim to increase awareness and knowledge of local biodiversity and to promote positive attitudes and behaviour towards the environment. However, limited research has been conducted evaluating to what extent these interventions achieve their goals. Here, we explore and assess the influence of a six-week bird-feeding and monitoring project conducted within school grounds ("Bird Buddies") on individual awareness, knowledge and attitudes towards birds by primary school children. This initiative was conducted across eight (sub-)urban primary schools within Brighton and Hove (UK), with 220 participating children (aged 7 to 10). Via pre- and post-project questionnaires, we found evidence for enhanced awareness of local biodiversity, alongside significant gains in both bird identification knowledge and attitudes, which were greatest for children with little prior exposure to nature. Many children expressed a keenness to continue improving the environmental value of their school grounds and to apply elements of the project at home. Student project evaluation scores were consistently positive. Mirroring this, participating teachers endorsed the project as a positive learning experience for their students. One year after the project, several schools were continuing to feed and watch birds. Collectively, the findings from this study highlight the multiple benefits that can be derived from engagement with a relatively short outdoor environmental activity. We therefore believe that such interventions, if repeated locally/longer term, could enhance children's experience with nature in urban settings with combined positive environmental impact

Modélisation numérique des matériaux granulaires immergés : applications aux avalanches sous-marines

Les avalanches sous marines apparaissant au voisinage des cotes constituent un risque majeur pour les structures offshores.Les mécanismes mis en jeu lors de leur évolution restent mal connus.Ils dépendent notamment de la pente ou de la quantité de matériau déstabilisé.Dans cette étude on aborde leur modélisation par une approche couplée entre la méthode de Dynamique des Contacts pour les interactions entre grains et Lattice Boltzmann pour les interactions fluide-grains.On s'intéresse notamment aux distances de propagation en fonction de la géométrie initiale et les paramètres rhéologiques

Destabilization of immersed granular avalanches

By means of 3D coupled molecular dynamics/Lattice Boltzmann simulations, we analyzethe destabilization process of a granular bed of spherical particles inclined above its angleof repose and immersed in a viscous fluid [1]. Extensive simulations were performed fordifferent values of the packing fraction and slope angle. We study the evolution ofmacroscopic observables such as shear strain, packing fraction and excess pore pressure.We then analyze the contact network anisotropy. Two regimes are evidenced as inexperiments [2,3]: a loose regime where the slope fails spontaneously and a dense regimewhere the failure is delayed as a result of negative excess pore pressure built up inreaction to the dilation of the bed. The two regimes belong to the packing fractions belowand above 0.59, respectively. We focus in more detail on the creep-like deformation of theinclined bed in the dense regime. The time evolution of the packing fraction and shearstrain scale with a characteristic time obtained from a model based on the balance ofgranular stresses in the presence of a pore excess pressure and the relation of the latterwith dilatancy controlled by Darcian drag forces. The cumulative shear strain at failure isfound to be around 0.2, close to the experimental value [2], irrespective of the initialpacking fraction and inclination angle. In the same way, the time and packing fraction atfailure are correctly predicted by the model. A noticeable finding is that the networkdeforms by distortion at nearly constant connectivity. The contact network anisotropygrows with shear strain, and slope failure is triggered when the anisotropy levels off. Theanisotropy thus appears as an internal variable, reflecting the distortion of the contactnetwork. The independence of the internal friction angle with respect to the initial packingfraction and its dependence on the slope angle were studied and shown to be aconsequence of slope stabilization by the cohesive-like effect of negative excess porepressure. It is also interesting to note that the transition from stable equilibrium to inertialflow in the presence of a fluid is accompanied by large fluctuations. As soon as thecapacity of volume change by distortion is nearly exhausted, slope instability is triggeredby the fluctuations and amplified by lubrication forces as the avalanches proceeds

Numerical modeling of underwater avalanches

International audienc