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Julius B. Kirkegaard

Publications and source records attributed to Julius B. Kirkegaard.

17 recordsLinked to original sources

Extremal Contours: Gradient-driven contours for compact visual attribution

Faithful yet compact explanations for vision models remain a challenge, as commonly used dense perturbation masks are often fragmented and overfitted, needing careful post-processing. Here, we present a training-free explanation method that replaces dense masks with smooth tunable contours. A star-convex region is parameterized by a truncated Fourier series and optimized under an extremal preserve/delete objective using the classifier gradients. The approach guarantees a single, simply connected mask, cuts the number of free parameters by orders of magnitude, and yields stable boundary updates without cleanup. Restricting solutions to low-dimensional, smooth contours makes the method robust to adversarial masking artifacts. On ImageNet classifiers, it matches the extremal fidelity of dense masks while producing compact, interpretable regions with improved run-to-run consistency. Explicit area control also enables importance contour maps, yielding a transparent fidelity-area profiles. Finally, we extend the approach to multi-contour and show how it can localize multiple objects within the same framework. Across benchmarks, the method achieves higher relevance mass and lower complexity than gradient and perturbation based baselines, with especially strong gains on self-supervised DINO models where it improves relevance mass by over 15% and maintains positive faithfulness correlations.

cs.CV

Local Clustering and Global Spreading of Receptors for Optimal Spatial Gradient Sensing

Spatial information from cell-surface receptors is crucial for processes that require signal processing and sensing of the environment. Here, we investigate the optimal placement of such receptors through a theoretical model that minimizes uncertainty in gradient estimation. Without requiring a priori knowledge of the physical limits of sensing or biochemical processes, we reproduce the emergence of clusters that closely resemble those observed in real cells. On perfect spherical surfaces, optimally placed receptors spread uniformly. When perturbations break their symmetry, receptors cluster in regions of high curvature, massively reducing estimation uncertainty. This agrees with mechanistic models that minimize elastic preference discrepancies between receptors and cell membranes. We further extend our model to motile receptors responding to cell-shape changes and external fluid flow, demonstrating the relevance of our model in realistic scenarios. Our findings provide a simple and utilitarian explanation for receptor clustering at high-curvature regions when high sensing accuracy is paramount.

physics.bio-ph

Spline refinement with differentiable rendering

Detecting slender, overlapping structures remains a challenge in computational microscopy. While recent coordinate-based approaches improve detection, they often produce less accurate splines than pixel-based methods. We introduce a training-free differentiable rendering approach to spline refinement, achieving both high reliability and sub-pixel accuracy. Our method improves spline quality, enhances robustness to distribution shifts, and shrinks the gap between synthetic and real-world data. Being fully unsupervised, the method is a drop-in replacement for the popular active contour model for spline refinement. Evaluated on C. elegans nematodes, a popular model organism for drug discovery and biomedical research, we demonstrate that our approach combines the strengths of both coordinate- and pixel-based methods.

eess.IV

Adaptive Node Positioning in Biological Transport Networks

Biological transport networks are highly optimized structures that ensure power-efficient distribution of fluids across various domains, including animal vasculature and plant venation. Theoretically, these networks can be described as space-embedded graphs, and rich structures that align well with observations emerge from optimizing their hydrodynamic energy dissipation. Studies on these models typically use regular grids and focus solely on edge width optimization. Here, we present a generalization of the hydrodynamic graph model which permits additional optimization of node positioning. We achieve this by defining sink regions, accounting for the energy dissipation of delivery within these areas, and optimizing by means of differentiable physics. In the context of leaf venation patterns, our method results in organic networks that adapt to irregularities of boundaries and node misalignment, as well as overall improved efficiency. We study the dependency of the emergent network structures on the capillary delivery conductivity and identify a phase transition in which the network collapses below a critical threshold. Our findings provide insights into the early formation of biological systems and the efficient construction of transport networks.

physics.bio-ph

Modeling Full-Scale Leaf Venation Networks

The vascular network of leaves, comprising xylem and phloem, is a highly optimized system for the delivery of water, nutrients, and sugars. The design rules for these naturally occurring networks have been studied since the time of Leonardo da Vinci, who constructed a local rule for comparing the widths of in- and outgoing veins at branch points. Recently, physical models have been developed that seek to explain the full morphogenesis of leaf venial networks in which veins grow in response to local hydrodynamic feedback. Although these models go beyond simple local rules, they are challenging to compare to experimental data. Here, we extend these hydrodynamic models to a state where the direct comparison with images of full leaves becomes possible on the level of individual veins. We present a dataset of the venial networks of leaves that maintain full network topology and use this to discuss the benefits and drawbacks of such a direct comparison. We apply our approach to the direct estimation of a sink fluctuation parameter, demonstrating consistency within distinct leaf species. Finally, we utilize the ability of the model to run on full leaves to define and calculate exponents for a Murray's law that applies to reticulate venation networks.

physics.bio-ph

Persistent pseudopod splitting is an effective chemotaxis strategy in shallow gradients

Single-cell organisms and various cell types use a range of motility modes when following a chemical gradient, but it is unclear which mode is best suited for different gradients. Here, we model directional decision-making in chemotactic amoeboid cells as a stimulus-dependent actin recruitment contest. Pseudopods extending from the cell body compete for a finite actin pool to push the cell in their direction until one pseudopod wins and determines the direction of movement. Our minimal model provides a quantitative understanding of the strategies cells use to reach the physical limit of accurate chemotaxis, aligning with data without explicit gradient sensing or cellular memory for persistence. To generalize our model, we employ reinforcement learning optimization to study the effect of pseudopod suppression, a simple but effective cellular algorithm by which cells can suppress possible directions of movement. Different pseudopod-based chemotaxis strategies emerge naturally depending on the environment and its dynamics. For instance, in static gradients, cells can react faster at the cost of pseudopod accuracy, which is particularly useful in noisy, shallow gradients where it paradoxically increases chemotactic accuracy. In contrast, in dynamics gradients, cells form de novo pseudopods. Overall, our work demonstrates mechanical intelligence for high chemotaxis performance with minimal cellular regulation.

q-bio.CB

Learning optimal integration of spatial and temporal information in noisy chemotaxis

We investigate the boundary between chemotaxis driven by spatial estimation of gradients and chemotaxis driven by temporal estimation. While it is well known that spatial chemotaxis becomes disadvantageous for small organisms at high noise levels, it is unclear whether there is a discontinuous switch of optimal strategies or a continuous transition exists. Here, we employ deep reinforcement learning to study the possible integration of spatial and temporal information in an a priori unconstrained manner. We parameterize such a combined chemotactic policy by a recurrent neural network and evaluate it using a minimal theoretical model of a chemotactic cell. By comparing with constrained variants of the policy, we show that it converges to purely temporal and spatial strategies at small and large cell sizes, respectively. We find that the transition between the regimes is continuous, with the combined strategy outperforming in the transition region both the constrained variants as well as models that explicitly integrate spatial and temporal information. Finally, by utilizing the attribution method of integrated gradients, we show that the policy relies on a non-trivial combination of spatially and temporally derived gradient information in a ratio that varies dynamically during the chemotactic trajectories.

cs.NE

Fast spline detection in high density microscopy data

Computer-aided analysis of biological microscopy data has seen a massive improvement with the utilization of general-purpose deep learning techniques. Yet, in microscopy studies of multi-organism systems, the problem of collision and overlap remains challenging. This is particularly true for systems composed of slender bodies such as crawling nematodes, swimming spermatozoa, or the beating of eukaryotic or prokaryotic flagella. Here, we develop a novel end-to-end deep learning approach to extract precise shape trajectories of generally motile and overlapping splines. Our method works in low resolution settings where feature keypoints are hard to define and detect. Detection is fast and we demonstrate the ability to track thousands of overlapping organisms simultaneously. While our approach is agnostic to area of application, we present it in the setting of and exemplify its usability on dense experiments of crawling Caenorhabditis elegans. The model training is achieved purely on synthetic data, utilizing a physics-based model for nematode motility, and we demonstrate the model's ability to generalize from simulations to experimental videos.

cs.CV

Emerging Diversity in a Population of Evolving Intransitive Dice

Exploiting the mathematical curiosity of intransitive dice, we present a simple theoretical model for co-evolution that captures scales ranging from the genome of the individual to the system-wide emergence of species diversity. We study a set of evolving agents that interact competitively in a closed system, in which both the dynamics of mutations and competitive advantage emerge directly from interpreting a genome as the sides of a die. The model demonstrates sympatric speciation where new species evolve from existing ones while in contact with the entire ecosystem. Allowing free mutations both in the genomes and the mutation rates, we find, in contrast to hierarchical models of fitness, the emergence of a metastable state of finite mutation rate and diversity.

q-bio.PE

Optimal Transport Flows for Distributed Production Networks

Network flows often exhibit a hierarchical tree-like structure that can be attributed to the minimisation of dissipation. The common feature of such systems is a single source and multiple sinks (or vice versa). In contrast, here we study networks with only a single source and sink. These systems can arise from secondary purposes of the networks, such as blood sugar regulation through insulin production. Minimisation of dissipation in these systems lead to trivial behaviour. We show instead how optimising the transport time yields network topologies that match those observed in the insulin-producing pancreatic islets. These are patterns of periphery-to-center and center-to-periphery flows. The obtained flow networks are broadly independent of how the flow velocity depends on the flow flux, but continuous and discontinuous phase transitions appear at extreme flux dependencies. Lastly, we show how constraints on flows can lead to buckling of the branches of the network, a feature that is also observed in pancreatic islets.

q-bio.TO

Self-assembly, Buckling & Density-Invariant Growth of Three-dimensional Vascular Networks

The experimental actualisation of organoids modelling organs from brains to pancreases has revealed that much of the diverse morphologies of organs are emergent properties of simple intercellular "rules" and not the result of top-down orchestration. In contrast to other organs, the initial plexus of the vascular system is formed by aggregation of cells in the process known as vasculogenesis. Here we study this self-assembling process of blood vessels in three dimensions through a set of simple rules that align intercellular apical-basal and planar cell polarity. We demonstrate that a fully connected network of tubes emerges above a critical initial density of cells. Through planar cell polarity our model demonstrates convergent extension, and this polarity furthermore allows for both morphology-maintaining growth and growth-induced buckling. We compare this buckling to the special vasculature of Islets of Langerhans in the pancreas and suggest that the mechanism behind the vascular density-maintaining growth of these islets could be the result of growth-induced buckling.

q-bio.TO

The role of tumbling frequency and persistence in optimal run-and-tumble chemotaxis

One of simplest examples of navigation found in nature is run-and-tumble chemotaxis. Tumbles reorient cells randomly, and cells can drift toward attractants or away from repellents by biasing the frequency of these events. The post-tumble swimming directions are typically correlated with those prior, as measured by the variance of the reorientation angle distribution. This variance can range from large, in the case of bacteria, to so small that tumble events are imperceptible, as observed in choanoflagellates. This raises the question of optimality: why is such a range of persistence observed in nature? Here we study persistent run-and-tumble dynamics, focusing first on the optimisation of the linearised chemotactic response within the two-dimensional parameter space of tumble frequency and angular persistence. Although an optimal persistence does exist for a given tumble frequency, in the full parameter space there is a continuum of optimal solutions. Introducing finite tumble times that depend on the persistence can change this picture, illuminating one possible method for selecting tumble persistence based on species-specific reorientation dynamics. Moving beyond linear theory we find that optimal chemotactic strengths exist, and that these maximise reaction when swimming in a wrong direction, but have little or no reaction when swimming with even the slightest projection along the chemoattractant gradient.

cond-mat.soft

Mechanics and Variability of Cell Sheet Folding in the Embryonic Inversion of $Volvox$

Many embryonic deformations during development are the global result of local cell shape changes and other local active cell sheet deformations. Morphogenesis does not only therefore rely on the ability of the tissue to produce these active deformations, but also on the ability to regulate them in such a way as to overcome the intrinsic variability of and geometric constraints on the tissue. Here, we explore the interplay of regulation and variability in the green alga $Volvox$, whose spherical embryos turn themselves inside out to enable motility. Through a combination of light sheet microscopy and theoretical analysis, we quantify the variability of this inversion and analyse its mechanics in detail to show how shape variability arises from a combination of geometry, mechanics, and active regulation.

cond-mat.soft

Intra-chain organisation of hydrophobic residues controls inter-chain aggregation rates of amphiphilic polymers

Aggregation of amphiphiles through the action of hydrophobic interactions is a common feature in soft condensed matter systems and is of particular importance in the context of biophysics as it underlies both the generation of functional biological machinery as well as the formation of pathological misassembled states of proteins. Here we explore the aggregation behaviour of amphiphilic polymers using lattice Monte-Carlo calculations and show that the distribution of hydrophobic residues within the polymer sequence determines the facility with which dry/wet interfaces can be created and that such interfaces drive the aggregation process.

physics.bio-ph

Filter-feeding, near-field flows, and the morphologies of colonial choanoflagellates

Efficient uptake of nutrients from the environment is an important component in the fitness of all microorganisms, and its dependence on size may reveal clues to the origins of evolutionary transitions to multicellularity. Because potential benefits in uptake rates must be viewed in the context of other costs and benefits of size, such as varying predation rates and the increased metabolic costs associated with larger and more complex body plans, the uptake rate itself is not necessarily that which is optimized by evolution. Uptake rates can be strongly dependent on local organism geometry and its swimming speed, providing selective pressure for particular arrangements. Here we examine these issues for choanoflagellates, filter-feeding microorganisms that are the closest relatives of the animals. We explore the different morphological variations of the choanoflagellete $Salpingoeca~rosetta$, which can exist as a swimming cell, a sessile thecate cell, and as colonies of cells in various shapes. In the absence of other requirements and in a homogeneously nutritious environment, we find that the optimal strategy to maximize filter feeding by the collar of microvilli is to swim fast, which favours swimming unicells. In large external flows, the sessile thecate cell becomes advantageous. Effects of prey diffusion are discussed and also found to be to the advantage of the swimming unicell.

cond-mat.soft

Aerotaxis in the Closest Relatives of Animals

As the closest unicellular relatives of animals, choanoflagellates serve as useful model organisms for understanding the evolution of animal multicellularity. An important factor in animal evolution was the increasing ocean oxygen levels in the Precambrian, which are thought to have influenced the emergence of complex multicellular life. As a first step in addressing these conditions, we study here the response of the colony-forming choanoflagellate $Salpingoeca~rosetta$ to oxygen gradients. Using a microfluidic device that allows spatio-temporal variations in oxygen concentrations, we report the discovery that $S.~rosetta$ display positive aerotaxis. Analysis of the spatial population distributions provides evidence for logarithmic sensing of oxygen, which enhances sensing in low oxygen neighborhoods. Analysis of search strategy models on the experimental colony trajectories finds that choanoflagellate aerotaxis is consistent with stochastic navigation, the statistics of which are captured using an effective continuous version based on classical run-and-tumble chemotaxis.

cond-mat.soft

Motility of Colonial Choanoflagellates and the Statistics of Aggregate Random Walkers

We illuminate the nature of the three-dimensional random walks of microorganisms composed of individual organisms adhered together. Such $aggregate~random~walkers$ are typified by choanoflagellates, eukaryotes that are the closest living relatives of animals. In the colony-forming species $Salpingoeca~rosetta$ we show that the beating of each flagellum is stochastic and uncorrelated with others, and the vectorial sum of the flagellar propulsion manifests as stochastic helical swimming. A quantitative theory for these results is presented and species variability discussed.

cond-mat.soft