V.m. Savage

V.m. Savage
University of California, Los Angeles | UCLA · Department of Biomathematics

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151
Publications
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Introduction
Skills and Expertise

Publications

Publications (151)
Article
Full-text available
Aims: Bacterial response to temperature changes can influence their pathogenicity to plants and humans. Changes in temperature can affect cellular and physiological responses in bacteria that can in turn affect the evolution and prevalence of antibiotic-resistance genes. Yet, how antibiotic-resistance genes influence microbial temperature response...
Article
Full-text available
Assessing the impacts of anthropogenic degradation and climate change on global carbon cycling is hindered by a lack of clear, flexible and easy‐to‐use productivity models along with scarce trait and productivity data for parameterizing and testing those models. We provide a simple solution: a mechanistic framework (RS‐CFM) that combines remotely‐s...
Preprint
Although natural populations are typically subjected to multiple stressors, most past research has focused on single stressors and two-stressor interactions, with little attention paid to higher-order interactions among three or more stressors. However, higher-order interactions increasingly appear to be widespread. Consequently, we used a recently...
Article
Full-text available
Biological allometries, such as the scaling of metabolism to mass, are hypothesized to result from natural selection to maximize how vascular networks fill space yet minimize internal transport distances and resistance to blood flow. Metabolic scaling theory argues two guiding principles—conservation of fluid flow and space-filling fractal distribu...
Article
Full-text available
Temperature variation-through time and across climatic gradients-affects individuals, populations, and communities. Yet how the thermal response of biological systems is altered by environmental stressors is poorly understood. Here, we quantify two key features-optimal temperature and temperature breadth-to investigate how temperature responses var...
Article
Organismal locomotion mediates ecological interactions and shapes community dynamics. Locomotion is constrained by intrinsic and environmental factors and integrating these factors should clarify how locomotion affects ecology across scales. We extended general theory based on metabolic scaling and biomechanics to predict the scaling of five locomo...
Article
Full-text available
The rapid increase of multi-drug resistant bacteria has led to a greater emphasis on multi-drug combination treatments. However, some combinations can be suppressive—that is, bacteria grow faster in some drug combinations than when treated with a single drug. Typically, when studying interactions, the overall effect of the combination is only compa...
Article
Full-text available
Branching in vascular networks and in overall organismic form is one of the most common and ancient features of multicellular plants, fungi and animals. By combining machine-learning techniques with new theory that relates vascular form to metabolic function, we enable novel classification of diverse branching networks—mouse lung, human head and to...
Article
Full-text available
Ecosystem stability is a central question both in theoretical and applied biology. Dynamical systems theory can be used to analyze how growth rates, carrying capacities, and patterns of species interactions affect the stability of an ecosystem. The response to increasing complexity has been extensively studied and the general conclusion is that the...
Article
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Understanding how stressors combine to affect population abundances and trajectories is a fundamental ecological problem with increasingly important implications worldwide. Generalisations about interactions among stressors are challenging due to different categorisation methods and how stressors vary across species and systems. Here, we propose us...
Article
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Sleep serves disparate functions, most notably neural repair, metabolite clearance and circuit reorganization. Yet the relative importance remains hotly debated. Here, we create a novel mechanistic framework for understanding and predicting how sleep changes during ontogeny and across phylogeny. We use this theory to quantitatively distinguish betw...
Article
Dynamical shifts between the extremes of stability and collapse are hallmarks of ecological systems. These shifts are limited by and change with biodiversity, complexity, and the topology and hierarchy of interactions. Most ecological research has focused on identifying conditions for a system to shift from stability to any degree of instability—sp...
Article
Full-text available
Spatially continuous data on functional diversity will improve our ability to predict global change impacts on ecosystem properties. We applied methods that combine imaging spectroscopy and foliar traits to estimate remotely sensed functional diversity in tropical forests across an Amazon-to-Andes elevation gradient (215 to 3537 m). We evaluated th...
Preprint
Full-text available
Sleep serves disparate functions, most notably neural repair, metabolite clearance and circuit reorganization, yet the relative importance of these functions remains hotly debated. Here, we create a novel mechanistic framework for understanding and predicting how sleep changes during ontogeny (why babies sleep twice as long as adults) and across ph...
Article
Full-text available
Understanding constraints on consumer-resource body size-ratios is fundamentally important from both ecological and evolutionary perspectives. By analyzing data on 4,685 consumer-resource interactions from nine ecological communities, we show that in spatially complex environments—where consumers can forage in both two (2D, e.g., benthic zones) and...
Article
Full-text available
Cities, wealth, and earthquakes follow continuous power-law probability distributions such as the Pareto distribution, which are canonically associated with scale-free behavior and self-similarity. However, many self-similar processes manifest as discrete steps that do not produce a continuous scale-free distribution. We construct a discrete power-...
Preprint
Full-text available
Branching in vascular networks and in overall organismic form is one of the most common and ancient features of multicellular plants, fungi and animals. These networks deliver resources and eliminate wastes from early development onward, and even play a vital role in the growth, prognosis, and treatment of tumors and stroke recovery. Because of the...
Article
Full-text available
Much ecological research aims to explain how climate impacts biodiversity and ecosystem-level processes through functional traits that link environment with individual performance. However, the specific climatic drivers of functional diversity across space and time remain unclear due largely to limitations in the availability of paired trait and cl...
Article
Full-text available
Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied...
Article
Full-text available
Interactions are ubiquitous and have been extensively studied in many ecological, evolutionary, and physiological systems. A variety of measures—ANOVA, covariance, epistatic additivity, mutual information, joint cumulants, Bliss independence—exist that compute interactions across fields. However, these are not discussed and derived within a single,...
Article
Full-text available
Antibiotics select for resistant bacteria whose existence and emergence is more likely in populations with high phenotypic and genetic diversity. Identifying the mechanisms that generate this diversity can thus have clinical consequences for drug-resistant pathogens. We show here that intermediate levels of antibiotics are associated with higher le...
Article
Full-text available
Environmental factors like temperature, pressure, and pH partly shaped the evolution of life. As life progressed, new stressors (e.g., poisons and antibiotics) arose as part of an arms race among organisms. Here we ask if cells co-opted existing mechanisms to respond to new stressors, or whether new responses evolved de novo. We use a network-clust...
Preprint
Full-text available
Drug combinations are a promising strategy to increase killing efficiency and to decrease the likelihood of evolving resistance. A major challenge is to gain a detailed understanding of how drugs interact in a dose-specific manner, especially for interactions involving more than two drugs. Here we introduce a direct and intuitive visual representat...
Article
Full-text available
In animals, gas exchange between blood and tissues occurs in narrow vessels, whose diameter is comparable to that of a red blood cell. Red blood cells must deform to squeeze through these narrow vessels, transiently blocking or occluding the vessels they pass through. Although the dynamics of vessel occlusion have been studied extensively, it remai...
Data
Predicted cell fluxes with variability in Se spacing. (TIF)
Data
Data on zebrafish geometry. (PDF)
Data
Phase separation model. (TIF)
Data
Predicted cell flux in notch mutant zebrafish. (TIF)
Data
Regression on red blood cell velocity data for all 12 Se vessels in a 4dpf zebrafish. (TIF)
Data
Oxygenation model, phase separation model, derivation of the mean field model, and the effect of network perturbation on red blood cell partitioning. (PDF)
Preprint
Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied...
Article
Full-text available
Background In drug-drug interactions, there are surprising cases in which the growth inhibition of bacteria by a single antibiotic decreases when a second antibiotic is added. These interactions are termed suppressive and have been argued to have the potential to limit the evolution of resistance. Nevertheless, little attention has been given to su...
Article
Using drugs in combination can be important in therapeutic strategies, both to decrease the risk of toxic side effects as well as to decrease the likelihood of resistance evolving. These properties are largely affected by interactions among drugs. Given the increased use of three or more drugs in clinics, we provide a review of challenges researche...
Article
Full-text available
How a particular attribute of an organism changes or scales with its body size is known as an allometry. Biological allometries, such as metabolic scaling, have been hypothesized to result from selection to maximize how vascular networks fill space yet minimize internal transport distances and resistances. The West, Brown, Enquist (WBE) model argue...
Data
Lagrange Multipliers On Asymmetric Networks. (PDF)
Data
Deriving the Metabolic Scaling Exponent for an Asymmetric Vascular Network with a Sharp Generational Transition. (PDF)
Data
Asymmetric Branching and Murray’s Law. (PDF)
Data
Symmetric/Difference Formalism of Asymmetric Branching. (PDF)
Data
Colormap of Metabolic Scaling Exponent for Pulsatile Flow Using Symmetric/Difference Formalism. (PDF)
Data
Animated Colormap of Metabolic Scaling Exponent for an Asymmetric Vascular Network with a Sharp Generational Transition. (MP4)
Data
Evolution of Asymmetric Network Morphology Along 3/4 Metabolic Scaling Exponent Contour for Pulsatile Flow. (MPG)
Article
Understanding how multiple stressors interact is needed to predict the dynamical outcomes of diverse biological systems, ranging from drug-resistant pathogens that are combated and treated with combination drug therapies to ecosystems impacted by environmental toxicants or disturbances. Nevertheless, extensive studies of higher-order (more than two...
Article
Full-text available
Modern models that derive allometric relationships between metabolic rate and body mass are based on the architectural design of the cardiovascular system and presume sibling vessels are symmetric in terms of radius, length, flow rate, and pressure. Here, we study the cardiovascular structure of the human head and torso and of a mouse lung based on...
Data
Detailed proofs for the branching angle optimization solutions. (PDF)
Data
Planarity of local branching junctions in mouse and human networks. When the parent and child vessels are colocalized in the same plane, the junction is considered planar. (a) We quantify the planarity measure of local branching is by the scaled distance formula given here. When the scaled distance is equal to 0, the branching is perfectly planar....
Data
Type of optimal branching solution and analysis of Murray’s Law. Non-degenerate solutions (branching occurs) are specified with white, and degenerate solutions (junction collapses to vessel endpoint so no branching) are specified with black. The red color represents the region where the Generalized Murray’s law holds (scaling exponent d ∈ [2,3]), w...
Data
Histogram of branching angles and optimal branching angles of MC (material-cost) optimizations for mouse and human networks. All histograms show a unimodal distribution with means given by the red vertical lines. (PDF)
Data
Fraction of degenerate and non-degenerate branching solutions for material-cost optimizations. The surface-area constraint leads to degenerate solutions for (a) 26% (= 163/633) of branching junctions in the mouse lung network and (b) 34% (= 309/914) of branching junctions for the human head and torso network. Volume constraint leads to degenerate s...
Data
Comparison of real data for vascular networks versus random simulations of branching junctions for human head and torso network. The real and simulated networks (via local to global constraints) are separated by different columns. A schematic small network is given to describe how different simulations are performed. The vessels and the fixed end p...
Data
Heat map (color map) representation of the equivalent impedance (i.e., Zeq) for PC-0 (power-cost optimization for a single branching junction). The optimal branching location, J, for different choice of cost parameters (hi) and end points (Vi) is marked with a green dot. The optimal branching junction coincides with the end point V0 in panel (a), V...
Data
Junction-level comparison of optimal versus actual branching angles for the surface-area constraint of material-cost optimizations. Results for (a) mouse lung and (b) human head and torso. The Pearson correlation coefficients are calculated for each plot. (PDF)
Data
Computing branching angles from extracted vessel skeleton. We calculate branching angles as angles between the straight lines defined by the positional coordinates of the vessels—the endpoint coordinates V0, V1, V2, and J—at the bifurcation. (PDF)
Data
Statistical analysis of branching angle and optimal branching angle distributions from material-cost (MC) optimizations for mouse, human, and combined networks. (PDF)
Data
Details on the empirical data and the choice of parameters. (PDF)
Data
Iterations for randomly branching networks with intermediate constraints. The vessels and the fixed end points for the real branching network are in red. The random branching simulations start from this real networks, and newly resulting branching locations and vessels are shown in black. (1) The first simulation starts by randomly positioning the...
Data
The list of intensity thresholds and the version of Angicart utilized in this study and Newberry et al. [29]. (PDF)
Data
The percentage of non-deformed vessels in the Angicart outputs of human head and torso and mouse lung data. A vessel is identified as non-deformed when the number of voxels outside a distance rad+1 from the centerline of the vessel is less than the 10% of the total voxels of the vessel segment [29, 43]. (PDF)
Data
Murray’s law and optimal branching angle solutions. (PDF)
Article
Whether the thermal sensitivity of an organism's traits follows the simple Boltzmann-Arrhenius model remains a contentious issue that centers around consideration of its operational temperature range and whether the sensitivity corresponds to one or a few underlying rate-limiting enzymes. Resolving this issue is crucial, because mechanistic models...
Article
Understanding how multiple stressors interact is needed to predict the dynamical outcomes of diverse biological systems, ranging from drug-resistant pathogens that are combated and treated with combination drug therapies to ecosystems impacted by environmental toxicants or disturbances. Nevertheless, extensive studies of higher-order (more than two...
Article
Understanding how multiple stressors interact is needed to predict the dynamical outcomes of diverse biological systems, ranging from drug-resistant pathogens that are combated and treated with combination drug therapies to ecosystems impacted by environmental toxicants or disturbances. Nevertheless, extensive studies of higher-order (more than two...
Chapter
Full-text available
A major challenge in biology is to predict eco-evolutionary dynamics—coupled changes in the ecological dynamics of population density and the evolution of phenotypic (functional trait) variation within and between species—of entire communities and ecosystems. Although mathematical and computational tools allow eco-evolutionary dynamics to be simula...
Article
Full-text available
Abstract Trophic cascades are indirect positive effects of predators on resources via control of intermediate consumers. Larger-bodied predators appear to induce stronger trophic cascades (a greater rebound of resource density toward carrying capacity), but how this happens is unknown because we lack a clear depiction of how the strength of trophic...