Engineering synthetic phosphorylation signaling networks in human cells.

Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation circuits in human cells. Our design scheme enabled model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, and downstream connections can regulate gene expression.

A universal niche geometry governs the response of ecosystems to environmental perturbations.

How ecosystems respond to environmental perturbations is a fundamental question in ecology, made especially challenging due to the strong coupling between species and their environment. Here, we introduce a theoretical framework for calculating the steady-state response of ecosystems to environmental perturbations in generalized consumer-resource. Our construction is applicable to a wide class of systems, including models with non-reciprocal interactions, cross-feeding, and non-linear growth/consumption rates.

Integrating local energetics into Maxwell-Calladine constraint counting to design mechanical metamaterials.

The Maxwell-Calladine index theorem plays a central role in our current understanding of the mechanical rigidity of discrete materials. By considering the geometric constraints each material component imposes on a set of underlying degrees of freedom, the theorem relates the emergence of rigidity to constraint counting arguments. However, the Maxwell-Calladine paradigm is significantly limited-its exclusive reliance on the geometric relationships between constraints and degrees of freedom completely neglects the actual energetic costs of deforming individual components.

Phase Transition to Chaos in Complex Ecosystems with Nonreciprocal Species-Resource Interactions.

Nonreciprocal interactions between microscopic constituents can profoundly shape the large-scale properties of complex systems. Here, we investigate the effects of nonreciprocity in the context of theoretical ecology by analyzing a generalization of MacArthur's consumer-resource model with asymmetric interactions between species and resources. Using a mixture of analytic cavity calculations and numerical simulations, we show that such ecosystems generically undergo a phase transition to chaotic dynamics as the amount of nonreciprocity is increased.

A universal niche geometry governs the response of ecosystems to environmental perturbations.

How ecosystems respond to environmental perturbations is a fundamental question in ecology, made especially challenging due to the strong coupling between species and their environment. Here, we introduce a theoretical framework for calculating the linear response of ecosystems to environmental perturbations in generalized consumer-resource models. Our construction is applicable to a wide class of systems, including models with non-reciprocal interactions, cross-feeding, and non-linear growth/consumption rates.

Phase transition to chaos in complex ecosystems with non-reciprocal species-resource interactions.

Non-reciprocal interactions between microscopic constituents can profoundly shape the large-scale properties of complex systems. Here, we investigate the effects of non-reciprocity in the context of theoretical ecology by analyzing a generalization of MacArthur's consumer-resource model with asymmetric interactions between species and resources. Using a mixture of analytic cavity calculations and numerical simulations, we show that such ecosystems generically undergo a phase transition to chaotic dynamics as the amount of non-reciprocity is increased.

Emergent competition shapes top-down versus bottom-up control in multi-trophic ecosystems.

Ecosystems are commonly organized into trophic levels-organisms that occupy the same level in a food chain (e.g., plants, herbivores, carnivores).

Engineering synthetic phosphorylation signaling networks in human cells.

Protein phosphorylation signaling networks play a central role in how cells sense and respond to their environment. Here, we describe the engineering of artificial phosphorylation networks in which "push-pull" motifs-reversible enzymatic phosphorylation cycles consisting of opposing kinase and phosphatase activities-are assembled from modular protein domain parts and then wired together to create synthetic phosphorylation circuits in human cells. We demonstrate that the composability of our design scheme enables model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, while downstream connections can regulate gene expression.

Phase transition to chaos in complex ecosystems with non-reciprocal species-resource interactions.

Non-reciprocal interactions between microscopic constituents can profoundly shape the large-scale properties of complex systems. Here, we investigate the effects of non-reciprocity in the context of theoretical ecology by analyzing a generalization of MacArthur's consumer-resource model with asymmetric interactions between species and resources. Using a mixture of analytic cavity calculations and numerical simulations, we show that such ecosystems generically undergo a phase transition to chaotic dynamics as the amount of non-reciprocity is increased.

Ultra-high throughput mapping of genetic design space.

Massively parallel genetic screens have been used to map sequence-to-function relationships for a variety of genetic elements. However, because these approaches only interrogate short sequences, it remains challenging to perform high throughput (HT) assays on constructs containing combinations of sequence elements arranged across multi-kb length scales. Overcoming this barrier could accelerate synthetic biology; by screening diverse gene circuit designs, "composition-to-function" mappings could be created that reveal genetic part composability rules and enable rapid identification of behavior-optimized variants.

Emergent competition shapes the ecological properties of multi-trophic ecosystemss.

Ecosystems are commonly organized into trophic levels - organisms that occupy the same level in a food chain (e.g., plants, herbivores, carnivores).

Memorizing without overfitting: Bias, variance, and interpolation in overparameterized models.

The bias-variance trade-off is a central concept in supervised learning. In classical statistics, increasing the complexity of a model (e.g.

Bias-variance decomposition of overparameterized regression with random linear features.

In classical statistics, the bias-variance trade-off describes how varying a model's complexity (e.g., number of fit parameters) affects its ability to make accurate predictions.

Correlation of plastic events with local structure in jammed packings across spatial dimensions.

In frictionless jammed packings, existing evidence suggests a picture in which localized physics dominates in low spatial dimensions, d = 2, 3, but quickly loses relevance as d rises, replaced by spatially extended mean-field behavior. For example, quasilocalized low-energy vibrational modes and low-coordination particles associated with deviation from mean-field behavior (rattlers and bucklers) all vanish rapidly with increasing d. These results suggest that localized rearrangements, which are associated with low-energy vibrational modes, correlated with local structure, and dominant in low dimensions, should give way in higher d to extended rearrangements uncorrelated with local structure.

Hidden Topological Structure of Flow Network Functionality.

The ability to reroute and control flow is vital to the function of venation networks across a wide range of organisms. By modifying individual edges in these networks, either by adjusting edge conductances or creating and destroying edges, organisms robustly control the propagation of inputs to perform specific tasks. However, a fundamental disconnect exists between the structure and function: networks with different local architectures can perform the same functions.

Limits of multifunctionality in tunable networks.

Nature is rife with networks that are functionally optimized to propagate inputs to perform specific tasks. Whether via genetic evolution or dynamic adaptation, many networks create functionality by locally tuning interactions between nodes. Here we explore this behavior in two contexts: strain propagation in mechanical networks and pressure redistribution in flow networks.

Designing allostery-inspired response in mechanical networks.

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds.

Monte Carlo renormalization-group analysis of percolation.

We describe a Monte Carlo renormalization group approach to the calculation of critical behavior for percolation models. This approach can be utilized to determine the renormalized bond probabilities and the values of the critical exponents. We illustrate the method for two-dimensional bond percolation, but the method is also applicable to other percolation models and other dimensions.

Negative-mass instability in nonlinear plasma waves.

The negative-mass instability, previously found in ion traps, appears as a distinct regime of the sideband instability in nonlinear plasma waves with trapped particles. As the bounce frequency of these particles decreases with the bounce action, bunching can occur if the action distribution is inverted in trapping islands. In contrast to existing theories that also infer instabilities from the anharmonicity of bounce oscillations, spatial periodicity of the islands turns out to be unimportant, and the particle distribution can be unstable even if it is flat at the resonance.

Nonlinear amplification and decay of phase-mixed waves in compressing plasma.

Through particle-in-cell simulations, we show that plasma waves carrying trapped electrons can be amplified manyfold via compressing plasma perpendicularly to the wave vector. These simulations are the first ab initio demonstration of the conservation of nonlinear action for such waves, which contains a term independent of the field amplitude. In agreement with the theory, the maximum of amplification gain is determined by the total initial energy of the trapped-particle average motion but otherwise is insensitive to the particle distribution.

The epidemiology of published norovirus outbreaks: a review of risk factors associated with attack rate and genogroup.

The purpose of this study was to examine global epidemiological trends in human norovirus (NoV) outbreaks by transmission route and setting, and describe relationships between these characteristics, viral attack rates, and the occurrence of genogroup I (GI) or genogroup II (GII) strains in outbreaks. We analysed data from 902 reverse transcriptase-polymerase chain reaction-confirmed, human NoV outbreaks abstracted from a systematic review of articles published from 1993 to 2011 and indexed under the terms 'norovirus' and 'outbreak'. Multivariate regression analyses demonstrated that foodservice and winter outbreaks were significantly associated with higher attack rates.

Collegiate athletic trainers' knowledge and perceptions of disordered eating behaviors in athletes.

To assess athletic trainers' perceptions and knowledge regarding disordered eating behaviors and to estimate their confidence in response to a test of knowledge, a cross-sectional mail survey was distributed to a national random sample of 500 athletic trainers from the National Collegiate Athletic Association and National Association of Intercollegiate Athletics. 408 collegiate certified athletic trainers responded (rate of 81.6%).

Intrinsic shoulder pain syndrome: rationale for heating and cooling in treatment.

This article reviews the literature on pathology and symptoms of the major intrinsic shoulder pain syndromes. Treatment rationale for heating and cooling agents is suggested, based on the pathology of the syndromes and the physiological effects of the agents.