arXiv subjects

Jean M. Carlson

Publications and source records attributed to Jean M. Carlson.

At least 19 recordsLinked to original sources

arXiv2020

Aging-induced fragility of the immune system

The adaptive and innate branches of the vertebrate immune system work in close collaboration to protect organisms from harmful pathogens. As an organism ages its immune system undergoes immunosenescence, characterized by declined performance or malfunction in either immune branch, which can lead to disease and death. In this study we develop a mathematical framework of coupled innate and adaptive immune responses, namely the integrated immune branch (IIB) model. This model describes dynamics of immune components in both branches, uses a shape-space representation to encode pathogen-specific immune memory, and exhibits three steady states -- health, septic death, and chronic inflammation -- qualitatively similar to clinically-observed immune outcomes. In this model, the immune system (initialized in the health state) is subjected to a sequence of pathogen encounters, and we use the number of prior pathogen encounters as a proxy for the "age" of the immune system. We find that repeated pathogen encounters may trigger a fragility in which any encounter with a novel pathogen will cause the system to irreversibly switch from health to chronic inflammation. This transition is consistent with the onset of "inflammaging", a condition observed in aged individuals who experience chronic low-grade inflammation even in the absence of pathogens. The IIB model predicts that the onset of chronic inflammation strongly depends on the history of encountered pathogens; the timing of onset differs drastically when the same set of infections occurs in a different order. Lastly, the coupling between the innate and adaptive immune branches generates a trade-off between rapid pathogen clearance and a delayed onset of immunosenescence.

q-bio.TO↗

arXiv2020

Navigation and control of outcomes in a generalized Lotka-Volterra model of the microbiome

The generalized Lotka-Volterra (gLV) equations model the microbiome as a collection of interacting ecological species. Here we use a particular experimentally-derived gLV model of C. difficile infection (CDI) as a case study to generate methods that are applicable to generic gLV models. We examine how to transition gLV systems between multiple steady states through the application of direct control protocols, which alter the state of the system via the instantaneous addition or subtraction of microbial species. Then, the geometry of the basins of attraction of point attractors is compressed into an attractor network, which decomposes a multistable high-dimensional landscape into web of bistable subsystems. This attractor network is used to identify efficient (total intervention volume minimizing) protocols that drive the system from one basin to another. In some cases, the most efficient control protocol is circuitous and will take the system through intermediate steady states with sequential interventions. Clinically, the efficient control of the microbiome has pertinent applications for bacteriotherapies, which seek to remedy microbiome-affiliated diseases by directly altering the composition of the gut microbiome.

q-bio.PE↗

arXiv2020

Control of ecological outcomes through deliberate parameter changes in a model of the gut microbiome

The generalized Lotka-Volterra (gLV) equations are a mathematical proxy for ecological dynamics. We focus on a gLV model of the gut microbiome, in which the evolution of the gut microbial state is determined in part by pairwise inter-species interaction parameters that encode environmentally-mediated resource competition between microbes. We develop an in silico method that controls the steady-state outcome of the system by adjusting these interaction parameters. This approach is confined to a bistable region of the gLV model. The two steady states of interest are idealized as either a "healthy" or "diseased" steady state of the gut microbiome. In this method, a dimensionality reduction technique called steady-state reduction (SSR) is first used to generate a two-dimensional (2D) gLV model that approximates the high-dimensional dynamics on the 2D subspace spanned by the two steady states. Then a bifurcation analysis of the 2D model analytically determines parameter modifications that drive a disease-prone initial condition to the healthy steady state. This parameter modification of the reduced 2D model guides parameter modifications of the original high-dimensional model, resulting in a change of steady-state outcome in the high-dimensional model. This control method, called SPARC (SSR-guided parameter change), bypasses the computational challenge of directly determining parameter modifications in the original high-dimensional system. SPARC could guide the development of indirect bacteriotherapies, which seek to change microbial compositions by deliberately modifying gut environmental variables such as gut acidity or macronutrient availability.

q-bio.PE↗

arXiv2019

Characterization of fracture in topology-optimized bio-inspired networks

Designing strong and robust bio-inspired structures requires an understanding of how function arises from the architecture and geometry of materials found in nature. We draw from trabecular bone, a lightweight bone tissue that exhibits a complex, anisotropic microarchitecture, to generate networked structures using multi-objective topology optimization. Starting from an identical volume, we generate multiple different models by varying the objective weights for compliance, surface area, and stability. We examine the relative effects of these objectives on how resultant models respond to simulated mechanical loading and element failure. We adapt a network-based method developed initially in the context of modeling trabecular bone to describe the topology-optimized structures with a graph theoretical framework, and we use community detection to characterize locations of fracture. This complementary combination of computational methods can provide valuable insights into the strength of bio-inspired structures and mechanisms of fracture.

physics.bio-ph↗

arXiv2019

Network models for characterization of trabecular bone

Trabecular bone is a lightweight, compliant material organized as a web of struts and rods (trabeculae) that erode with age and the onset of bone diseases like osteoporosis, leading to increased fracture risk. The traditional diagnostic marker of osteoporosis, bone mineral density (BMD), has been shown in ex vivo experiments to correlate poorly with fracture resistance when considered on its own, while structural features in conjunction with BMD can explain more of the variation in trabecular bone strength. We develop a network-based model of trabecular bone by creating graphs from micro-computed tomography images of human bone, with weighted links representing trabeculae and nodes representing branch points. These graphs enable calculation of quantitative network metrics to characterize trabecular structure. We also create finite element models of the networks in which each link is represented by a beam, facilitating analysis of the mechanical response of the bone samples to simulated loading. We examine the structural and mechanical properties of trabecular bone at the scale of individual trabeculae (of order 0.1 mm) and at the scale of selected volumes of interest (approximately a few mm), referred to as VOIs. At the VOI scale, we find significant correlations between the stiffness of VOIs and 10 different structural metrics. Individually, the volume fraction of each VOI is most strongly correlated to the stiffness of the VOI. We use multiple linear regression to identify the smallest subset of variables needed to capture the variation in stiffness. In a linear fit, we find that node degree, weighted node degree, Z-orientation, weighted Z-orientation, trabecular spacing, link length, and the number of links are the structural metrics that are most significant (p < 0.05) in capturing the variation of stiffness in trabecular networks.

physics.med-ph↗

arXiv2019

Steady State Reduction of generalized Lotka-Volterra systems in the microbiome

The generalized Lotka-Volterra (gLV) equations, a classic model from theoretical ecology, describe the population dynamics of a set of interacting species. As the number of species in these systems grow in number, their dynamics become increasingly complex and intractable. We introduce Steady State Reduction (SSR), a method that reduces a gLV system of many ecological species into two-dimensional (2D) subsystems that each obey gLV dynamics and whose basis vectors are steady states of the high-dimensional model. We apply this method to an experimentally-derived model of the gut microbiome in order to observe the transition between "healthy" and "diseased" microbial states. Specifically, we use SSR to investigate how fecal microbiota transplantation, a promising clinical treatment for dysbiosis, can revert a diseased microbial state to health.

q-bio.PE↗

arXiv2016

Collective Decision Dynamics in Group Evacuation: Behavioral Experiment and Machine Learning Models

Identifying factors that affect human decision making and quantifying their influence remain essential and challenging tasks for the design and implementation of social and technological communication systems. We report results of a behavioral experiment involving decision making in the face of an impending natural disaster. In a controlled laboratory setting, we characterize individual and group evacuation decision making influenced by several key factors, including the likelihood of the disaster, available shelter capacity, group size, and group decision protocol. Our results show that success in individual decision making is not a strong predictor of group performance. We use an artificial neural network trained on the collective behavior of subjects to predict individual and group outcomes. Overall model accuracy increases with the inclusion of a subject-specific performance parameter based on laboratory trials that captures individual differences. In parallel, we demonstrate that the social media activity of individual subjects, specifically their Facebook use, can be used to generate an alternative individual personality profile that leads to comparable model accuracy. Quantitative characterization and prediction of collective decision making is crucial for the development of effective policies to guide the action of populations in the face of threat or uncertainty.

physics.soc-ph↗

arXiv2016

Collective Decision Dynamics in Group Evacuation: Modeling Tradeoffs and Optimal Behavior

Quantifying uncertainties in collective human behavior and decision making is crucial for ensuring public health and safety, enabling effective disaster response, informing the design of transportation and communication networks, and guiding the development of new technologies. However, modeling and predicting such behavior is notoriously difficult, due to the influence of a variety of complex factors such as the availability and uncertainty of information, the interaction and influence of social groups and networks, the degree of risk or time pressure involved in a situation, and differences in individual personalities and preferences. Here, we develop a stochastic model of human decision making to describe the empirical behavior of subjects in a controlled experiment simulating a natural disaster scenario. We compare the observed behavior to that of statistically optimal Bayesian decision makers, quantifying the extent to which human decisions are optimal and identifying the conditions in which sub-optimal decisions are made. Finally, we investigate how human evacuation strategies change when decisions are made in groups under a variety of different rules, and whether these group strategy adjustments are optimal or beneficial.

physics.soc-ph↗

arXiv2016

Individual Differences in Dynamic Functional Brain Connectivity Across the Human Lifespan

Individual differences in brain functional networks may be related to complex personal identifiers, including health, age, and ability. Understanding and quantifying these differences is a necessary first step towards developing predictive methods derived from network topology. Here, we present a method to quantify individual differences in brain functional dynamics by applying hypergraph analysis, a method from dynamic network theory. Using a summary metric derived from the hypergraph formalism---hypergraph cardinality---we investigate individual variations in two separate and complementary data sets. The first data set ("multi-task") consists of 77 individuals engaging in four consecutive cognitive tasks. We observed that hypergraph cardinality exhibits variation across individuals while remaining consistent within individuals between tasks; moreover, one of the memory tasks evinced a marginally significant correspondence between hypergraph cardinality and age. This finding motivated a similar analysis of the second data set ("age-memory"), in which 95 individuals of varying ages performed a memory task with a similar structure to the multi-task memory task. With the increased age range in the age-memory data set, the correlation between hypergraph cardinality and age correspondence becomes significant. We discuss these results in the context of the well-known finding linking age with network structure, and suggest that age-related changes in brain function can be better understood by taking an integrative approach that incorporates information about the dynamics of functional interactions.

q-bio.NC↗

arXiv2016

Optimizing Real-Time Vaccine Allocation in a Stochastic SIR Model

Real-time vaccination following an outbreak can effectively mitigate the damage caused by an infectious disease. However, in many cases, available resources are insufficient to vaccinate the entire at-risk population, logistics result in delayed vaccine deployment, and the interaction between members of different cities facilitates a wide spatial spread of infection. Limited vaccine, time delays, and interaction (or coupling) of cities lead to tradeoffs that impact the overall magnitude of the epidemic. These tradeoffs mandate investigation of optimal strategies that minimize the severity of the epidemic by prioritizing allocation of vaccine to specific subpopulations. We use an SIR model to describe the disease dynamics of an epidemic which breaks out in one city and spreads to another. We solve a master equation to determine the resulting probability distribution of the final epidemic size. We then identify tradeoffs between vaccine, time delay, and coupling, and we determine the optimal vaccination protocols resulting from these tradeoffs.

q-bio.PE↗

arXiv2014

Coevolutionary immune system dynamics driving pathogen speciation

We introduce and analyze a within-host dynamical model of the coevolution between rapidly mutating pathogens and the adaptive immune response. Pathogen mutation and a homeostatic constraint on lymphocytes both play a role in allowing the development of chronic infection, rather than quick pathogen clearance. The dynamics of these chronic infections display emergent structure, including branching patterns corresponding to asexual pathogen speciation, which is fundamentally driven by the coevolutionary interaction. Over time, continued branching creates an increasingly fragile immune system, and leads to the eventual catastrophic loss of immune control.

q-bio.PE↗

arXiv2014

Brain Network Adaptability Across Task States

Activity in the human brain moves between diverse functional states to meet the demands of our dynamic environment, but fundamental principles guiding these transitions remain poorly understood. Here, we capitalize on recent advances in network science to analyze patterns of functional interactions between brain regions. We use dynamic network representations to probe the landscape of brain reconfigurations that accompany task performance both within and between four cognitive states: a task-free resting state, an attention-demanding state, and two memory-demanding states. Using the formalism of hypergraphs, we identify the presence of groups of functional interactions that fluctuate coherently in strength over time both within (task-specific) and across (task-general) brain states. In contrast to prior emphases on the complexity of many dyadic (region-to-region) relationships, these results demonstrate that brain adapt- ability can be described by common processes that drive the dynamic integration of cognitive systems. Moreover, our results establish the hypergraph as an effective measure for understanding functional brain dynamics, which may also prove useful in examining cross-task, cross-age, and cross-cohort functional change.

q-bio.NC↗

arXiv2014

Optimal vaccination in a stochastic epidemic model of two non-interacting populations

Developing robust, quantitative methods to optimize resource allocations in response to epidemics has the potential to save lives and minimize health care costs. In this paper, we develop and apply a computationally efficient algorithm that enables us to calculate the complete probability distribution for the final epidemic size in a stochastic Susceptible-Infected-Recovered (SIR) model. Based on these results, we determine the optimal allocations of a limited quantity of vaccine between two non-interacting populations. We compare the stochastic solution to results obtained for the traditional, deterministic SIR model. For intermediate quantities of vaccine, the deterministic model is a poor estimate of the optimal strategy for the more realistic, stochastic case.

q-bio.QM↗

arXiv2014

Grain fragmentation in sheared granular flow: weakening effects, energy dissipation, and strain localization

We describe the shear flow of a disordered granular material in the presence of grain fracture using the shear-transformation-zone (STZ) theory of amorphous plasticity adapted to systems with a hard-core inter-particle interaction. To this end, we develop the equations of motion for this system within a statistical-thermodynamic framework analogous to that used in the analysis of molecular glasses. For hard-core systems, the amount of internal, configurational disorder is characterized by the compactivity $X = \partial V / \partial S_C$, where $V$ and $S_C$ are respectively the volume and configurational entropy. Grain breakage is described by a constitutive equation for the temporal evolution of a characteristic grain size $a$, based on fracture mechanics. We show that grain breakage is a weakening mechanism, significantly lowering the flow stress at large strain rates, if the material is rate-strengthening in character. We show in addition that if the granular material is sufficiently aged, spatial inhomogeneity in configurational disorder results in strain localization. We also show that grain splitting contributes significantly to comminution at small shear strains, while grain abrasion becomes dominant at large shear displacements.

cond-mat.soft↗

arXiv2014

A two-scale model for sheared fault gouge: Competition between macroscopic disorder and local viscoplasticity

We develop a model for sheared gouge layers that accounts for the local increase in temperature at the grain contacts during sliding. We use the shear transformation zone (STZ) theory, a statistical thermodynamic theory, to describe irreversible macroscopic plastic deformations due to local rearrangements of the gouge particles. We track the temperature evolution at the grain contacts using a one dimensional heat diffusion equation. At low temperatures, the strength of the asperities is limited by the flow strength, as predicted by dislocation creep models. At high temperatures, some of the constituents of the grains may melt leading to the degradation of the asperity strength. Our model predicts a logarithmic rate dependence of the steady state shear stress in the quasi-static regime. In the dense flow regime the frictional strength decreases rapidly with increasing slip rate due to the effect of thermal softening at the granular interfaces. The transient response following a step in strain rate includes a direct effect and a following evolution effect, both of which depend on the magnitude and direction of the velocity step. In addition to frictional heat, the energy budget includes an additional energy sink representing the fraction of external work consumed in increasing local disorder. The model links low-speed and high-speed frictional response of gouge layers, and provides an essential ingredient for multiscale modeling of earthquake ruptures with enhanced coseismic weakening.

cond-mat.mtrl-sci↗

arXiv2013

Resolving Structure in Human Brain Organization: Identifying Mesoscale Organization in Weighted Network Representations

Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease.

q-bio.NC↗

arXiv2013

Measuring and Modeling Behavioral Decision Dynamics in Collective Evacuation

Identifying and quantifying factors influencing human decision making remains an outstanding challenge, impacting the performance and predictability of social and technological systems. In many cases, system failures are traced to human factors including congestion, overload, miscommunication, and delays. Here we report results of a behavioral network science experiment, targeting decision making in a natural disaster. In each scenario, individuals are faced with a forced "go" versus "no go" evacuation decision, based on information available on competing broadcast and peer-to-peer sources. In this controlled setting, all actions and observations are recorded prior to the decision, enabling development of a quantitative decision making model that accounts for the disaster likelihood, severity, and temporal urgency, as well as competition between networked individuals for limited emergency resources. Individual differences in behavior within this social setting are correlated with individual differences in inherent risk attitudes, as measured by standard psychological assessments. Identification of robust methods for quantifying human decisions in the face of risk has implications for policy in disasters and other threat scenarios.

physics.soc-ph↗

arXiv2013

Resolving structural variability in network models and the brain

Large-scale white matter pathways crisscrossing the cortex create a complex pattern of connectivity that underlies human cognitive function. Generative mechanisms for this architecture have been difficult to identify in part because little is known about mechanistic drivers of structured networks. Here we contrast network properties derived from diffusion spectrum imaging data of the human brain with 13 synthetic network models chosen to probe the roles of physical network embedding and temporal network growth. We characterize both the empirical and synthetic networks using familiar diagnostics presented in statistical form, as scatter plots and distributions, to reveal the full range of variability of each measure across scales in the network. We focus on the degree distribution, degree assortativity, hierarchy, topological Rentian scaling, and topological fractal scaling---in addition to several summary statistics, including the mean clustering coefficient, shortest path length, and network diameter. The models are investigated in a progressive, branching sequence, aimed at capturing different elements thought to be important in the brain, and range from simple random and regular networks, to models that incorporate specific growth rules and constraints. We find that synthetic models that constrain the network nodes to be embedded in anatomical brain regions tend to produce distributions that are similar to those extracted from the brain. We also find that network models hardcoded to display one network property do not in general also display a second, suggesting that multiple neurobiological mechanisms might be at play in the development of human brain network architecture. Together, the network models that we develop and employ provide a potentially useful starting point for the statistical inference of brain network structure from neuroimaging data.

q-bio.NC↗