Tractable Model Research Articles

The Large-Scale Cultivation of Nematodes to Study Their Collective Behaviors.

Animals exhibit dynamic collective behaviors, as observed in flocks of birds, schools of fish, and crowds of humans. The collective behaviors of animals have been investigated in the fields of both biology and physics. In the laboratory, researchers have used various model animals such as the fruit fly and zebrafish for approximately a century, but it has remained a major challenge to study large-scale complex collective behavior orchestrated by these genetically tractable model animals. This paper presents a protocol to create an experimental system of collective behaviors in Caenorhabditis elegans. The propagated worms climb on the lid of the Petri plate and show collective swarming behavior. The system also controls worm interactions and behaviors by changing the humidity and light stimulation. This system allows us to examine the mechanisms underlying collective behaviors by changing environmental conditions and examining the effects of individual-level locomotion on collective behaviors using mutants. Thus, the system is useful for future research in both physics and biology.

Using Burr Type XII distribution for user — Nearest access point distance modelling in finite Poisson networks with edge effect

Uniform Poisson Point Processes (uPPPs) have been extensively used for performance analysis of cellular networks. Of particular importance is the distribution of the distance between a user node (UE) and its closest access point (AP), which is useful for performance evaluation purposes. In this paper, the Burr Type XII distribution is proposed as a mathematically tractable statistical model of such distances in finite Poisson networks with the presence of edge effect. This result is further employed to evaluate the outage probability and ergodic capacity of Poisson networks in the presence of Nakagami-m fading. The accuracy of the proposed model is substantiated by simulations. Our newly derived results include as limiting cases existing ones available in the literature, namely Rayleigh distributed distances.

A Bayesian approach of the consequence of failure on inequality acceptance: Experimental evidence

AbstractIn this paper, we design a two‐stage experiment and a tractable model. The first stage is a tournament, and the second stage involves a hierarchical relationship where the loser of the tournament must declare what they think is an acceptable earnings distribution to have an incentive to work for the winner. We use a Becker–Degroot–Marschak (BDM) procedure to elicit the acceptable earnings distribution. We show that failure in the tournament could decrease the willingness to accept wage inequality and that this behavior relies on Bayesian updating. We identify a “fresh start” effect: When the asset required to win the tournament is not the same as the asset that the loser uses to produce after failure, inequality acceptance is higher.

Knock-out of vasotocin reduces reproductive success in female zebrafish, Danio rerio.

The vertebrate nonapeptide vasotocin/vasopressin is evolutionarily highly conserved and acts as neuromodulator and endocrine/paracrine signaling molecule. Circumstantial and mechanistic evidence from pharmacological manipulations of the vasotocin system in several teleost fishes suggest sex- and species-specific reproductive roles of vasotocin. While effects of vasotocin on teleost reproductive physiology involve both courtship behaviors and the regulation of the hypothalamic-pituitary-gonadal (HPG) axes, comprehensive studies investigating behavioral and physiological reproductive consequences of genetic ablation of vasotocin in a genetically tractable fish model, such as the zebrafish, are currently lacking. Here, we report the generation of homozygous CRISPR/Cas9-based vasotocin gene knock-out zebrafish. Breeding pairs of vasotocin knock-out fish produce significantly fewer fertilized eggs per clutch compared to wildtype fish, an effect coincident with reduced female quivering courtship behavior. Crossbreeding experiments reveal that this reproductive phenotype is entirely female-dependent, as vasotocin-deficient males reproduce normally when paired with female wild-type fish. Histological analyses of vasotocin knock-out ovaries revealed an overall reduction in oocytes and differential distribution of oocyte maturation stages, demonstrating that the reproductive phenotype is linked to oocyte maturation and release. Ovarian hormone quantification and gene expression analysis in mutant fish indicated reduced synthesis of Prostaglandin F2α, a hormone involved in ovarian maturation, egg release and regulation of female courtship behavior in some cyprinids. However, acute injection of vasotocin did not rescue the female mutant reproductive phenotype, suggesting a contribution of organizational effects of vasotocin. Together, this study provides further support for emerging roles of vasotocin in female teleost reproduction in an important teleost model species.

Quantitative easing rules as a means to achieve optimal levels of structural reforms and government deficits in a monetary union

AbstractThis paper uses a tractable game theory model to study the interactions of structural reforms and fiscal and monetary policies in the European Monetary Union (EMU). Considering the externalities that arise when interest rates have hit the lower bound and monetary policy is carried out through quantitative easing (QE), we show that the subgame perfect equilibrium is suboptimal when structural reforms and fiscal policy are implemented at a national level. Then, we prove that the optimal outcome cannot be obtained if structural reforms are dictated by a supranational institution. By contrast, we establish that the first best can be obtained either by a full‐fledged fiscal union or a rule on QE. Given the practical difficulties that the first of these two solutions have encountered in the EMU, a rule over QE provides a clear, easier and more credible way to make structural reforms and fiscal deficits achieve the levels that maximise the union's welfare.

Genetic diversity, recombination and cross-species transmission of a waterbird gammacoronavirus in the wild.

Viruses emerging from wildlife can cause outbreaks in humans and domesticated animals. Predicting the emergence of future pathogens and mitigating their impacts requires an understanding of what shapes virus diversity and dynamics in wildlife reservoirs. In order to better understand coronavirus ecology in wild species, we sampled birds within a coastal freshwater lagoon habitat across 5 years, focussing on a large population of mute swans (Cygnus olor) and the diverse species that they interact with. We discovered and characterised the full genome of a divergent gammacoronavirus belonging to the Goose coronavirus CB17 species. We investigated the genetic diversity and dynamics of this gammacoronavirus using untargeted metagenomic sequencing of 223 faecal samples from swans of known age and sex, and RT-PCR screening of 1632 additional bird samples. The virus circulated persistently within the bird community; virus prevalence in mute swans exhibited seasonal variations, but did not change with swan age-class or epidemiological year. One whole genome was fully characterised, and revealed that the virus originated from a recombination event involving an undescribed gammacoronavirus species. Multiple lineages of this gammacoronavirus co-circulated within our study population. Viruses from this species have recently been detected in aquatic birds from both the Anatidae and Rallidae families, implying that host species habitat sharing may be important in shaping virus host range. As the host range of the Goose coronavirus CB17 species is not limited to geese, we propose that this species name should be updated to 'Waterbird gammacoronavirus 1'. Non-invasive sampling of bird coronaviruses may provide a tractable model system for understanding the evolutionary and cross-species dynamics of coronaviruses.

Traveling waves in a coarse‐grained model of volume‐filling cell invasion: Simulations and comparisons

AbstractMany reaction–diffusion models produce traveling wave solutions that can be interpreted as waves of invasion in biological scenarios such as wound healing or tumor growth. These partial differential equation models have since been adapted to describe the interactions between cells and extracellular matrix (ECM), using a variety of different underlying assumptions. In this work, we derive a system of reaction–diffusion equations, with cross‐species density‐dependent diffusion, by coarse‐graining an agent‐based, volume‐filling model of cell invasion into ECM. We study the resulting traveling wave solutions both numerically and analytically across various parameter regimes. Subsequently, we perform a systematic comparison between the behaviors observed in this model and those predicted by simpler models in the literature that do not take into account volume‐filling effects in the same way. Our study justifies the use of some of these simpler, more analytically tractable models in reproducing the qualitative properties of the solutions in some parameter regimes, but it also reveals some interesting properties arising from the introduction of cell and ECM volume‐filling effects, where standard model simplifications might not be appropriate.

Recurrent laryngeal motor nerve conduction studies in a rat model: Establishing an objective measure for investigating laryngeal innervation.

Disease or injury can cause neuromuscular changes to the larynx that can affect voice, breathing, and swallowing. Motor nerve conduction studies have had limited use in the study of laryngeal neurophysiology, despite their importance in other anatomic sites. The aim of this study was to explore the feasibility of performing recurrent laryngeal motor nerve conduction studies (rlMNCS) in a rat model. rlMNCS were performed in 15 rats under anesthesia. A bipolar stimulating electrode was placed on the recurrent laryngeal nerve (RLN) 5 mm below the cricoid cartilage. Via direct laryngoscopy, a recording electrode was placed transorally into the thyroarytenoid muscle. The RLN was maximally stimulated to determine the compound muscle action potential (CMAP). Three consecutive trials were averaged. The mean stimulating threshold to the RLN to achieve a CMAP from the thyroarytenoid was 1.7 ± 0.6 mA. RLN stimulation caused a visible adductor twitch of the vocal fold in all animals. The mean negative amplitude was 2.0 ± 0.8 mV, and the total area was 1.0 ± 0.4 mV ms. The CMAP latency and negative duration were 1.0 ± 0.1 ms and 0.9 ± 0.2 ms, respectively. rlMNCS are feasible and may be useful in understanding laryngeal neurophysiology with disease or injury. This work could provide a tractable animal model for studying and monitoring treatment of neuromuscular conditions affecting voice, breathing, and swallowing.

Upstream migrant sea lamprey (Petromyzon marinus) show signs of increasing oxidative stress but maintain aerobic capacity with age

Following the parasitic juvenile phase of their life cycle, sea lamprey (Petromyzon marinus) mature into a reproductive but rapidly aging and deteriorating adult, and typically die shortly after spawning in May or June. However, pre-spawning upstream migrant sea lamprey can be maintained for several months beyond their natural lifespan when held in cold water (∼4-8 °C) under laboratory conditions. We exploited this feature to investigate the interactions between senescence, oxidative stress, and metabolic function in this phylogenetically ancient fish. We investigated how life history traits and mitochondria condition, as indicated by markers of oxidative stress (catalase activity, lipid peroxidation) and aerobic capacity (citrate synthase activity), changed in adult sea lamprey from June to December after capture during their upstream spawning migration. Body mass but not liver mass declined with age, resulting in an increase in hepatosomatic index. Both effects were most pronounced in males, which also tended to have larger livers than females. Lamprey experienced greater oxidative stress with age, as reflected by increasing activity of the antioxidant enzyme catalase and increasing levels of lipid peroxidation in liver mitochondrial isolates over time. Surprisingly, the activity of citrate synthase also increased with age in both sexes. These observations implicate mitochondrial dysfunction and oxidative stress in the senescence of sea lamprey. Due to their unique evolutionary position and the technical advantage of easily delaying the onset of senescence in lampreys using cold water, these animals could represent an evolutionary unique and tractable model to investigate senescence in vertebrates.

BSLD-05 ESTABLISHMENT AND CHARACTERIZATION OF MOUSE MODELS OF LEPTOMENINGEAL METASTASIS

Abstract There is critical need to study leptomeningeal metastasis (LM), a fatal complication of cancer accompanied by severe neurological deficits. LM occurs when cancer cells enter the leptomeninges, float in the cerebrospinal fluid (CSF), and adhere to the surface of the brain and spinal cord. Understanding the molecular basis of LM requires reliable models of the disease that can recapitulate the complex microenvironment that supports LM cell growth. Here, we define a protocol for iterative in vivo selection of cancer cells competent to colonize the leptomeninges (LeptoM cells) from a larger population of primary tumor cells that stably express GFP and luciferase. We use these LeptoM cells to establish tractable models of leptomeningeal disease in both syngeneic and xenograft mice. With these models, we modulate disease severity and capture snapshots of hallmark LM characteristics over time. We demonstrate the fidelity of these mouse models to human disease in several dimensions: 1. Biochemically, through CSF proteomics and metabolomics; 2. Immunologically, via flow cytometry and cytokine profiling; 3. Transcriptionally through RNA sequencing; and 4. Neurologically by accumulation of neurological signs. They are freely available to the academic community. These models provide robust, reproducible tools for discovery and mechanistic dissection. They will enable identification of critical disease mechanisms, and assays of novel treatment modalities against LM.

A fully robust home energy management model considering real time price and on-board vehicle batteries

On-board batteries from electric vehicles can be used in domestic installations as an auxiliary source of energy through their vehicle-to-home features. To properly manage this kind of assets, Home Energy Management systems are expected to be essential tools in future smart grids, enabling a more efficient use of energy in residential applications. However, these tools normally perform under severe uncertain environments caused by intermittent renewable generation, uncertain prices, uncertain demand as well as uncertain behaviour of electric vehicles. In this regard, further research should be conducted in order to develop advanced robust energy management tools that account for the effect of uncertainties. So far, most of the existing literature focused on simple stochastic approaches, that may pose various issues, while other more sophisticated uncertainty models have not been sufficiently studied. In this regard, this paper proposes a fully robust Home Energy Management model, which accounts for all the inherent uncertainties that may arise in domestic installations. In contrast to previous researches, robust optimization is applied to all the uncertainties, resulting in a tractable, but robust yet paradigm model which allows to adapt the degree of robustness. A case study is conducted on a benchmark prosumer paradigm to validate the new proposal as well as highlight the benefits of flexible appliances. Results reveal the usefulness of the new tool, which allows to handle very unfavourable uncertain profiles, especially in case of the electric vehicles, for which a very low initial state-of-charge and early departure time can be assumed, leading to more conservative results that suppose incrementing the electricity bill by 38 %.

Effects of the self-propulsion parity on the efficiency of a fuel-consuming active heat engine.

We propose a thermodynamically consistent, analytically tractable model of steady-state active heat engines driven by both temperature difference and a constant chemical driving. While the engine follows the dynamics of the active Ornstein-Uhlenbeck particle, its self-propulsion stems from the mechanochemical coupling with the fuel consumption dynamics, allowing for both even- and odd-parity self-propulsion forces. Using the standard methods of stochastic thermodynamics, we show that the entropy production of the engine satisfies the conventional Clausius relation, based on which we define the efficiency of the model that is bounded from above by the second law of thermodynamics. Using this framework, we obtain exact expressions for the efficiency at maximum power. The results show that the engine performance has a nonmonotonic dependence on the magnitude of the chemical driving and that the even-parity (odd-parity) engines perform better when the size of the engine is smaller (larger) than the persistence length of the active particle. We also discuss the existence of a tighter upper bound on the efficiency of the odd-parity engines stemming from the detailed structure of the entropy production.

Quantifying the Neural and Behavioral Correlates of Repeated Social Competition in the Fighting Fish Betta splendens

The fighting fish Betta splendens, long studied for its aggressive territorial competitions, has the potential to be a tractable and relevant model for studying the intersection of cognitive ecology and social neuroscience. Yet, few studies have comprehensively assessed Betta behavior across both social and nonsocial contexts. Furthermore, the present study is the first to quantify the expression of phosphorylated ribosomal protein S6 (PS6), a proxy for neural response, in the Betta telencephalon. Here, we assessed male Betta behavior across a suite of tasks and found that response to a mirror, but not neophilia (a novel object) nor anxiety (scototaxis), predicted behavior in a social competition. To then explore the cognitive aspects of social competition, we exposed Betta to either a familiar or novel opponent and compared their competitive behavior as well as their neural responses in the teleost homologs of the hippocampus, basolateral amygdala, and lateral septum. We did not detect any differences between familiar-exposed and novel-exposed individuals, but by implementing the first use of a habituation–dishabituation competition design in a study of Betta, we were able to observe remarkable consistency in competitive outcomes across repeated exposures. Taken together, the present study lays the groundwork for expanding the use of Betta to explore integrative and multidimensional questions of social cognition.

Intraocular Axon Regeneration in a Model of Penetrating Eye Injury.

Purpose: Penetrating eye injuries commonly cause permanent loss of vision in patients. Unlike mammals, zebrafish can regenerate both damaged tissue and severed axons in the central nervous system. Here, we present a tractable adult zebrafish model to study intraocular axon regeneration after penetrating eye injury. Methods: To create consistent penetrating intraocular injuries, pins of standardized diameters were inserted into the eye through the cornea and penetrating the retina but not the underlying sclera. Transgenic gap43:GFP reporter fish were used to preferentially label retinal ganglion cells (RGCs) that respond to injury with regenerating axons. Retinas were fixed and flat mounted at various times postinjury to examine injury size, number of green fluorescent protein (GFP)-positive cells and axons, axonal varicosities, and rate of regeneration to the optic nerve head. Intraocular injection of colchicine was used to inhibit axon outgrow as a proof of principle that this method can be used to screen effects of pharmacological agents on intraocular axon regeneration. Results: Penetrating injury to the zebrafish retina results in robust axon regeneration by RGCs around and beyond the site of injury. The gap43:GFP transgene allows visualization of individual or small bundles of axons with varicosities and growth cones easily observable. Regeneration proceeded with most, if not all, axons reaching the optic nerve head by 3-day postinjury. A single intraocular injection of colchicine a day after injury was sufficient to delay axon regeneration at 2-days postinjury. Surprisingly, we identified a stereotypically located population of circumferential projecting neurons within the retina that upregulate gap43:GFP expression after injury. Conclusions: Penetrating injury to the adult gap43:GFP transgenic zebrafish eye is a model of successful intraocular axon regeneration. The pharmacological and genetic tools available for this organism should make it a powerful tool for dissecting the cellular, molecular, and genetic mechanisms of axon regeneration in the intraocular environment.

Genetics of yellow-orange color variation in a pair of sympatric sulphur butterflies

Continuous color polymorphisms can serve as a tractable model for the genetic and developmental architecture of traits. Here we investigated continuous color variation in Colias eurytheme and Colias philodice, two species of sulphur butterflies that hybridize in sympatry. Using quantitative trait locus (QTL) analysis and high-throughput color quantification, we found two interacting large-effect loci affecting orange-to-yellow chromaticity. Knockouts of red Malpighian tubules (red), likely involved in endosomal maturation, result in depigmented wing scales. Additionally, the transcription factor bric-a-brac can act as a modulator of orange pigmentation. We also describe the QTL architecture of other continuously varying traits, together supporting a large-X effect model where the genetic control of species-defining traits is enriched on sex chromosomes. This study sheds light on the range of possible genetic architectures that can underpin a continuously varying trait and illustrates the power of using automated measurement to score phenotypes that are not always conspicuous to the human eye.

Fluorescent Probe for in Vivo Partitioning into Dynamic Lipid Droplets Enables Monitoring of Water Permeability-Induced Edema.

Lipid droplets (LDs) are intracellular organelles found in most cell types from adipocytes to cancer cells. Although recent investigations have implicated LDs in numerous diseases, the current available methods to monitor them in vertebrate models rely on static imaging using fluorescent dyes, limiting the investigation of their rapid in vivo dynamics. Here, we report a fluorophore chemistry approach to enable in vivo LD dynamic monitoring using a Nernstian partitioning mechanism. Interestingly, the effect of atorvastatin and osmotic treatments toward LDs revealed an unprecedented dynamic enhancement. Then, using a designed molecular probe with an optimized response to hydration and LD dynamics applied to Zebrafish developing pericardial and yolk-sac edema, which represents a tractable model of a human cardiovascular disease, we also provide a unique dual method to detect disease evolution and recovery.

Graph isomorphism: physical resources, optimization models, and algebraic characterizations

In the (G, H)-isomorphism game, a verifier interacts with two non-communicating players (called provers), by privately sending each of them a random vertex from either G or H. The goal of the players is to convince the verifier that the graphs G and H are isomorphic. In recent work along with Atserias et al. (J Comb Theory Ser B 136:89–328, 2019) we showed that a verifier can be convinced that two non-isomorphic graphs are isomorphic, if the provers are allowed to share quantum resources. In this paper we model classical and quantum graph isomorphism by linear constraints over certain complicated convex cones, which we then relax to a pair of tractable convex models (semidefinite programs). Our main result is a complete algebraic characterization of the corresponding equivalence relations on graphs in terms of appropriate matrix algebras. Our techniques are an interesting mix of algebra, combinatorics, optimization, and quantum information.

Distributionally robust chance‐constrained optimization with Sinkhorn ambiguity set

AbstractA novel distributionally robust chance‐constrained optimization (DRCCP) method is proposed in this work based on the Sinkhorn ambiguity set. The Sinkhorn ambiguity set is constructed based on the Sinkhorn distance, which is a variant of the Wasserstein distance with the entropic regularization. The proposed method can hedge against more general families of uncertainty distributions than the Wasserstein ambiguity set‐based methods. The presented approach is formulated as a tractable conic model based on the Conditional value‐at‐risk (CVaR) approximation and the discretized kernel distribution relaxation. This model is compatible with more general constraints that are subject to uncertainty than the Wasserstein‐based methods. Accordingly, the presented Sinkhorn DRCCP is a more practical approach that overcomes the limitations of the traditional Wasserstein DRCCP approaches. A numerical example and a nonlinear chemical process optimization case are studied to demonstrate the efficacy of the Sinkhorn DRCCP and its advantages over the Wasserstein DRCCP.

Creation of an albino squid line by CRISPR-Cas9 and its application for invivo functional imaging of neural activity.

Cephalopods are remarkable among invertebrates for their cognitive abilities, adaptive camouflage, novel structures, and propensity for recoding proteins through RNA editing. Due to the lack of genetically tractable cephalopod models, however, the mechanisms underlying these innovations are poorly understood. Genome editing tools such as CRISPR-Cas9 allow targeted mutations in diverse species to better link genes and function. One emerging cephalopod model, Euprymna berryi, produces large numbers of embryos that can be easily cultured throughout their life cycle and has a sequenced genome. As proof of principle, we used CRISPR-Cas9 in E.berryi to target the gene for tryptophan 2,3 dioxygenase (TDO), an enzyme required for the formation of ommochromes, the pigments present in the eyes and chromatophores of cephalopods. CRISPR-Cas9 ribonucleoproteins targeting tdo were injected into early embryos and then cultured to adulthood. Unexpectedly, the injected specimens were pigmented, despite verification of indels at the targeted sites by sequencing in injected animals (G0s). A homozygote knockout line for TDO, bred through multiple generations, was also pigmented. Surprisingly, a gene encoding indoleamine 2,3, dioxygenase (IDO), an enzyme that catalyzes the same reaction as TDO in vertebrates, was also present in E.berryi. Double knockouts of both tdo and ido with CRISPR-Cas9 produced an albino phenotype. We demonstrate the utility of these albinos for invivo imaging of Ca2+ signaling in the brain using two-photon microscopy. These data show the feasibility of making gene knockout cephalopod lines that can be used for live imaging of neural activity in these behaviorally sophisticated organisms.

Optimal Monetary Policy According to HANK

We study optimal monetary policy in an analytically tractable heterogeneous agent New Keynesian model with rich cross-sectional heterogeneity. Optimal policy differs from a representative agent benchmark because monetary policy can affect consumption inequality, by stabilizing consumption risk arising from both idiosyncratic shocks and unequal exposures to aggregate shocks. The trade-off between consumption inequality, productive efficiency, and price stability is summarized in a simple linear-quadratic problem yielding interpretable target criteria. Stabilizing consumption inequality requires putting some weight on stabilizing the level of output, and correspondingly reducing the weights on the output gap and price level relative to the representative agent benchmark. (JEL E12, E23, E31, E32, E52, E62)