Size Scaling Research Articles

Pharmacokinetic Pharmacodynamic Modelling Contributions to Improve Paediatric Anaesthesia Practice.

The use of pharmacokinetic-pharmacodynamic models has improved anaesthesia practice in children through a better understanding of dose-concentration-response relationships, developmental pharmacokinetic changes, quantification of drug interactions and insights into how covariates (e.g., age, size, organ dysfunction, pharmacogenomics) impact drug prescription. Simulation using information from these models has enabled the prediction and learning of beneficial and adverse effects and decision-making around clinical scenarios. Covariate information, including the use of allometric size scaling, age and consideration of fat mass, has reduced population parameter variability. The target concentration approach has rationalised dose calculation. Paediatric pharmacokinetic-pharmacodynamic insights have led to better drug delivery systems for total intravenous anaesthesia and an expectation about drug offset when delivery is stopped. Understanding concentration-dependent adverse effects have tempered dose regimens. Quantification of drug interactions has improved the understanding of the effects of drug combinations. Repurposed drugs (e.g., antiviral drugs used for COVID-19) within the community can have important effects on drugs used in paediatric anaesthesia, and the use of simulation educates about these drug vagaries.

Social Brain Energetics: Ergonomic Efficiency, Neurometabolic Scaling, and Metabolic Polyphenism in Ants.

Metabolism, a metric of the energy cost of behavior, plays a significant role in social evolution. Body size and metabolic scaling are coupled, and a socioecological pattern of increased body size is associated with dietary change and the formation of larger and more complex groups. These consequences of the adaptive radiation of animal societies beg questions concerning energy expenses, a substantial portion of which may involve the metabolic rates of brains that process social information. Brain size scales with body size, but little is understood about brain metabolic scaling. Social insects such as ants show wide variation in worker body size and morphology that correlates with brain size, structure, and worker task performance, which is dependent on sensory inputs and information-processing ability to generate behavior. Elevated production and maintenance costs in workers may impose energetic constraints on body size and brain size that are reflected in patterns of metabolic scaling. Models of brain evolution do not clearly predict patterns of brain metabolic scaling, nor do they specify its relationship to task performance and worker ergonomic efficiency, two key elements of social evolution in ants. Brain metabolic rate is rarely recorded and therefore the conditions under which brain metabolism influences the evolution of brain size are unclear. We propose that studies of morphological evolution, colony social organization, and worker ergonomic efficiency should be integrated with analyses of species-specific patterns of brain metabolic scaling to advance our understanding of brain evolution in ants.

Aggressive behaviour in the skyhoppers of the Australian Alps

The evolution of male-male aggression is of interest because at its extreme it can be very energetically costly, leave males vulnerable to preadtors, and give rise to weaponry such as exaggerated traits. In grasshoppers (Acrididae), one group stands out as exceptionally aggressive, the skyhoppers (Kosciuscola) in which males bite, kick, mandible flare, and wrestle each other for access to females or when females are laying eggs. In this study we asked whether there is variation in aggressive behaviour among four skyhopper species and aimed to determine whether the traits used in fighting bear signatures of sexual selection in their size, variability, and allometric scaling. We found clear differences in the numbers and types of aggressive behaviours among species. Kosciuscola tristis and K. usitatus were the most aggressive, K. cognatus was the least aggressive, and K. tristis was the only species that performed the ‘mandible flare’ behaviour. Mandible size was larger among the three species that showed aggressive behaviour, all except K. cognatus, and was negatively allometric for all species possibly suggesting a functional size constraint. Pronotum size was different among most species and K. tristis’ pronotum was the largest and borderline positively allometric perhaps suggesting that pronotum size is related to aggressive behaviour but the nature of that relationship remains obscured. Our study suggests that further work investigates skyhoppers’ aggressive behaviour and how it varies with ecology, and paves the way for establishing them as a model system in the evolution of aggressive behaviour.

Information-theoretic memory scaling in the many-body localization transition

A key feature of the many-body localized phase is the breaking of ergodicity and consequently the emergence of local memory; revealed as the local preservation of information over time. As memory is necessarily a time dependent concept, it has been partially captured by a few extant studies of dynamical quantities. However, these quantities are neither optimal, nor democratic with respect to input state; and as such a fundamental and complete information theoretic understanding of local memory in the context of many-body localization remains elusive. We introduce the dynamical Holevo quantity as the true quantifier of local memory, outlining its advantages over other quantities such as the imbalance or entanglement entropy. We find clear scaling behavior in its steady-state across the many-body localization transition, and determine a family of two-parameter scaling ans\"atze which captures this behavior. We perform a comprehensive finite size scaling analysis of this dynamical quantity extracting the transition point and scaling exponents.

Finite Element Simplifications and Simulation Reliability in Single Point Incremental Forming.

Single point incremental forming (SPIF) is one of the most promising technologies for the manufacturing of sheet metal prototypes and parts in small quantities. Similar to other forming processes, the design of the SPIF process is a demanding task. Nowadays, the design process is usually performed using numerical simulations and virtual models. The modelling of the SPIF process faces several challenges, including extremely long computational times caused by long tool paths and the complexity of the problem. Path determination is also a demanding task. This paper presents a finite element (FE) analysis of an incrementally formed truncated pyramid compared to experimental validation. Focus was placed on a possible simplification of the FE process modelling and its impact on the reliability of the results obtained, especially on the geometric accuracy of the part and bottom pillowing effect. The FE modelling of SPIF process was performed with the software ABAQUS, while the experiment was performed on a conventional milling machine. Low-carbon steel DC04 was used. The results confirm that by implementing mass scaling and/or time scaling, the required calculation time can be significantly reduced without substantially affecting the pillowing accuracy. An innovative artificial neural network (ANN) approach was selected to find the optimal values of mesh size and mass scaling in term of minimal bottom pillowing error. However, care should be taken when increasing the element size, as it has a significant impact on the pillow effect at the bottom of the formed part. In the range of selected mass scaling and element size, the smallest geometrical error regarding the experimental part was obtained by mass scaling of 19.01 and tool velocity of 16.49 m/s at the mesh size of 1 × 1 mm. The obtained results enable significant reduction of the computational time and can be applied in the future for other incrementally formed shapes as well.

Long-term experimental evolution decouples size and production costs in Escherichia coli

Body size covaries with population dynamics across life’s domains. Metabolism may impose fundamental constraints on the coevolution of size and demography, but experimental tests of the causal links remain elusive. We leverage a 60,000-generation experiment in which Escherichia coli populations evolved larger cells to examine intraspecific metabolic scaling and correlations with demographic parameters. Over the course of their evolution, the cells have roughly doubled in size relative to their ancestors. These larger cells have metabolic rates that are absolutely higher, but relative to their size, they are lower. Metabolic theory successfully predicted the relations between size, metabolism, and maximum population density, including support for Damuth’s law of energy equivalence, such that populations of larger cells achieved lower maximum densities but higher maximum biomasses than populations of smaller cells. The scaling of metabolism with cell size thus predicted the scaling of size with maximum population density. In stark contrast to standard theory, however, populations of larger cells grew faster than those of smaller cells, contradicting the fundamental and intuitive assumption that the costs of building new individuals should scale directly with their size. The finding that the costs of production can be decoupled from size necessitates a reevaluation of the evolutionary drivers and ecological consequences of biological size more generally.

Thermal Traits Vary with Mass and across Populations of the Marsh Periwinkle, Littoraria irrorata.

AbstractPhysiological processes influence how individuals perform in various environmental contexts. The basis of such processes, metabolism, scales allometrically with body mass and nonlinearly with temperature, as described by a thermal performance curve. Past studies of thermal performance curves tend to focus on effects of temperature on a single body size or population, rather than variation in the thermal performance curve across sizes and populations. Here, we estimate intraspecific variation in parameters of the thermal performance curve in the salt marsh gastropod Littoraria irrorata. First, we quantify the thermal performance curve for respiration rate as a function of both temperature and body size in Littoraria and evaluate whether the thermal parameters and body size scaling are interdependent. Next, we quantify how parameters in the thermal performance curve for feeding rate vary between three Littoraria populations that occur along a latitudinal gradient. Our work suggests that the thermal traits describing Littoraria respiration are dependent on body mass and that both the thermal traits and the mass scaling of feeding vary across sites. We found limited evidence to suggest that mass scaling of Littoraria feeding or respiration rates depends on temperature. Variation in the thermal performance curves interacts with the size structure of the Littoraria population to generate divergent population-level responses to temperature. These results highlight the importance of considering variation in population size structure and physiological allometry when attempting to predict how temperature change will affect physiological responses and consumer-resource interactions.

Specificity of Nuclear Size Scaling in Frog Erythrocytes.

In eukaryotes, the cell has the ability to modulate the size of the nucleus depending on the surrounding environment, to enable nuclear functions such as DNA replication and transcription. From previous analyses of nuclear size scaling in various cell types and species, it has been found that eukaryotic cells have a conserved scaling rule, in which the nuclear size correlates with both cell size and genomic content. However, there are few studies that have focused on a certain cell type and systematically analyzed the size scaling properties in individual species (intra-species) and among species (inter-species), and thus, the difference in the scaling rules among cell types and species is not well understood. In the present study, we analyzed the size scaling relationship among three parameters, nuclear size, cell size, and genomic content, in our measured datasets of terminally differentiated erythrocytes of five Anura frogs and collected datasets of different species classes from published papers. In the datasets of isolated erythrocytes from individual frogs, we found a very weak correlation between the measured nuclear and cell cross-sectional areas. Within the erythrocytes of individual species, the correlation of the nuclear area with the cell area showed a very low hypoallometric relationship, in which the relative nuclear size decreased when the cell size increased. These scaling trends in intra-species erythrocytes are not comparable to the known general correlation in other cell types. When comparing parameters across species, the nuclear areas correlated with both cell areas and genomic contents among the five frogs and the collected datasets in each species class. However, the contribution of genomic content to nuclear size determination was smaller than that of the cell area in all species classes. In particular, the estimated degree of the contribution of genomic content was greater in the amphibian class than in other classes. Together with our imaging analysis of structural components in nuclear membranes, we hypothesized that the observed specific features in nuclear size scaling are achieved by the weak interaction of the chromatin with the nuclear membrane seen in frog erythrocytes.

Surface energy of the one-dimensional supersymmetric [formula omitted] model with general integrable boundary terms in the antiferromagnetic sector

In this paper, we study the surface energy of the one-dimensional supersymmetric t−J model with nonparallel boundary magnetic fields, which is a typical U(1)-symmetry broken quantum integrable strongly correlated electron system. It is shown that at the ground state, the contribution of inhomogeneous term in the Bethe ansatz solution of eigenvalues of transfer matrix satisfies the finite size scaling law Lβ where β<0. Based on it, the physical quantities of the system in the thermodynamic limit are calculated. We obtain the patterns of Bethe roots, root densities, ground state energy and surface energy. We also find that there exist the stable boundary bound states if the boundary fields satisfy some constraints.

Kinetochore size scales with chromosome size in bimodal karyotypes of Agavoideae.

In eukaryotes, the total kinetochore size (defined as a chromosomal region containing CENH3-positive nucleosomes) per nucleus strongly correlates with genome size, a relationship that has been hypothesized to stem from general intracellular scaling principles. However, if larger chromosomes within a karyotype required larger kinetochores to move properly, it could also be derived from the mechanics of cell division. We selected seven species of the plant subfamily Agavoideae whose karyotypes are characterized by the presence of small and very large chromosomes. We visualized the kinetochore regions and chromosomes by immunolabelling with an anti-CENH3 antibody and DAPI (6'-diamidino-2-phenylindole) staining. We then employed 2D widefield and 3D super-resolution microscopy to measure chromosome and kinetochore areas and volumes, respectively. To assess the scaling relationship of kinetochore size to chromosome size inside a karyotype, we log-transformed the data and analysed them with linear mixed models which allowed us to control for the inherent hierarchical structure of the dataset (metaphases within slides and species). We found a positive intra-karyotype relationship between kinetochore and chromosome size. The slope of the regression line of the observed relationship (0.277 for areas, 0.247 for volumes) was very close to the theoretical slope of 0.25 for chromosome width based on the expected physics of chromosome passage through the cytoplasm during cell division. We obtained similar results by reanalysing available data from human and maize. Our findings suggest that the total kinetochore size to genome size scaling observed across eukaryotes may also originate from the mechanics of cell division. Moreover, the potential causal link between kinetochore and chromosome size indicates that evolutionary mechanisms capable of leading kinetochore size changes to fixation, such as centromere drive, could promote the size evolution of entire chromosomes and genomes.

Relative skull size evolution in Mesozoic archosauromorphs: potential drivers and morphological uniqueness of erythrosuchid archosauriforms

AbstractLittle is known about the large‐scale evolutionary patterns of skull size relative to body size, and the possible drivers behind these patterns, in Archosauromorpha. For example, the large skulls of erythrosuchids, a group of non‐archosaurian archosauromorphs from the Early and Middle Triassic, and of theropod dinosaurs are regarded as convergent adaptations for hypercarnivory. However, few investigations have explicitly tested whether erythrosuchid and theropod skulls are indeed disproportionately large for their body size, and whether this trend is driven by hypercarnivory. Here, we investigate archosauromorph relative skull size evolution, examining the scaling relationships between skull and body size of Palaeozoic and Mesozoic archosauromorphs using a robust phylogenetic framework and assessing the influence of potential drivers, such as taxonomy, diet, locomotory mode and inhabited biotope. Our results show that archosauromorph relative skull sizes are largely determined by phylogeny and that the other drivers have much weaker levels of influence. We find negative allometric scaling of skull size with respect to body size when all studied archosauromorphs are analysed. Within specific groups, skull size scales with positive allometry in non‐archosaurian archosauromorphs and, interestingly, scales isometrically in theropods. Ancestral reconstructions of skull–femur size ratio reveal a disproportionately large skull at the base of Erythrosuchidae and proportionately sized skulls at the bases of Theropoda, Carnosauria and Tyrannosauroidea. Relative skull sizes of erythrosuchids and theropods are therefore distinct from each other, indicating that disproportionately large skulls are not a prerequisite for hypercarnivory in archosauromorphs, and that erythrosuchids exhibit a bauplan unique among terrestrial Mesozoic carnivores.

Precision study of the continuum SU(3) Yang-Mills theory: How to use parallel tempering to improve on supercritical slowing down for first order phase transitions

We perform large scale simulations to characterize the transition in quenched QCD. It is shown by a rigorous finite size scaling that the transition is of first order. After this qualitative feature quantitative results are obtained with unprecedented precision: we calculate the transition temperature $w_0T_c$=0.25384(23), -- which is the first per-mill accurate result in QCD thermodynamics -- and the latent heat $\Delta E/T_c^4$=1.025(21)(27) in both cases carrying out controlled continuum and infinite volume extrapolations. As it is well known the cost of lattice simulations explodes in the vicinity of phase transitions, a phenomenon called critical slowing down for second order phase transitions and supercritical slowing down for first order phase transitions. We show that a generalization of the parallel tempering algorithm of Marinari and Parisi [Europhys. Lett. 19, 451 (1992)] originally for spin systems can efficiently overcome these difficulties even if the transition is of first order, like in the case of QCD without quarks, or with very heavy quarks. We also report on our investigations on the autocorrelation times and other details.

Gap Statistics for Confined Particles with Power-Law Interactions.

We consider the N particle classical Riesz gas confined in a one-dimensional external harmonic potential with power-law interaction of the form 1/r^{k}, where r is the separation between particles. As special limits it contains several systems such as Dyson's log-gas (k→0^{+}), the Calogero-Moser model (k=2), the 1D one-component plasma (k=-1), and the hard-rod gas (k→∞). Despite its growing importance, only large-N field theory and average density profile are known for general k. In this Letter, we study the fluctuations in the system by looking at the statistics of the gap between successive particles. This quantity is analogous to the well-known level-spacing statistics which is ubiquitous in several branches of physics. We show that the variance goes as N^{-b_{k}} and we find the k dependence of b_{k} via direct MonteCarlo simulations. We provide supporting arguments based on microscopic Hessian calculation and a quadratic field theory approach. We compute the gap distribution and study its system size scaling. Except in the range -1<k<0, we find scaling for all k>-2 with both Gaussian and non-Gaussian scaling forms.

General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review.

Target controlled infusion (TCI) is a clinically-available and widely-used computer-controlled method of drug administration, adjusting the drug titration towards user selected plasma- or effect-site concentrations, calculated according to pharmacokinetic-pharmacodynamic (PKPD) models. Although this technology is clinically available for several anaesthetic drugs, the contemporary commercialised PKPD models suffer from multiple limitations. First, PKPD models for anaesthetic drugs are developed using deliberately selected patient populations, often excluding the more challenging populations, such as children, obese or elderly patients, of whom the body composition or elimination mechanisms may be structurally different compared to the lean adult patient population. Separate PKPD models have been developed for some of these subcategories, but the availability of multiple PKPD models for a single drug increases the risk for invalid model selection by the user. Second, some models are restricted to the prediction of plasma-concentration without enabling effect-site controlled TCI or they identify the effect-site equilibration rate constant using methods other than PKPD modelling. Advances in computing and the emergence of globally collected databases has allowed the development of new “general purpose” PKPD models. These take on the challenging task of identifying the relationships between patient covariates (age, weight, sex, etc) and the volumes and clearances of multi-compartmental pharmacokinetic models applicable across broad populations from neonates to the elderly, from the underweight to the obese. These models address the issues of allometric scaling of body weight and size, body composition, sex differences, changes with advanced age, and for young children, changes with maturation and growth. General purpose models for propofol, remifentanil and dexmedetomidine have appeared and these greatly reduce the risk of invalid model selection. In this narrative review, we discuss the development, characteristics and validation of several described general purpose PKPD models for anaesthetic drugs.

GPR-Based Framework for Statistical Analysis of Gate Delay under NBTI and Process Variation Effects

With the aggressive scaling of feature size, Negative Bias Temperature Instability (NBTI) and Process Variation (PV) have become major issues for circuit reliability and yield. In this paper, we analyze the variation of gate delay by jointly considering NBTI and PV effects. Using Gaussian Process Regression (GPR) learning interface, a Statistical Gate Delay Extraction (SGDE) framework is proposed. Typical types of logic gates are simulated with commercial 28 nm technology for verifying the performance of SGDE in the experiment. Compared to the golden data, the results show that our proposed approach achieves minimal loss of accuracy with significant runtime speed-up.

Exact percolation probabilities for a square lattice: site percolation on a plane, cylinder, and torus

We have found analytical expressions (polynomials) of the percolation probability for site percolation on a square lattice of size L × L sites when considering a plane (the crossing probability in a given direction), a cylinder (spanning probability), and a torus (wrapping probability along one direction). Since some polynomials are extremely cumbersome, they are presented as separate files in supplemental material. The system sizes for which this was feasible varied up to L = 17 for a plane, up to L = 16 for a cylinder, and up to L = 12 for a torus. To obtain a percolation probability polynomial, all possible combinations of occupied and empty sites have to be taken into account. However, using dynamic programming along with some ideas related to the topology, we offer an algorithm which allows a significant reduction in the number of configurations requiring consideration. A rigorous formal description of the algorithm is presented. Divisibility properties of the polynomials have been rigorously proved. Reliability of the polynomials obtained have been confirmed by the divisibility tests. The wrapping probability polynomials on a torus provide a better estimate of the percolation threshold than that from the spanning probability polynomials. Surprisingly, even a naive finite size scaling analysis allows an estimate to be obtained of the percolation threshold p c = 0.592 69.

Size scaling of sea turtle reproduction may reconcile fundamental ecology and conservation strategies at the global scale

AbstractAimThe body size of marine megafauna can influence population dynamics because larger females have disproportionally greater reproductive output. We explored how this size scaling relationship can affect predictions of population size structure in nesting sea turtles by combining a phylogenetically controlled meta‐analysis with a long‐term field nesting survey.LocationGlobal (meta‐analysis) and Malaysia (field survey).Time periodPresent.Major taxa studiedSea turtles.MethodsWe extracted body size and reproductive parameters of all sea turtle species from the literature and estimated the reproductive‐energy output using allometric models. We then examined the relationship between body size and the proportion of protected nesting beaches by country as an indicator of conservation efforts on body size. Long‐term monitoring (1993–2019) of body size and nesting data on green turtles (Chelonia mydas) from Redang Island (Malaysia) was used to examine temporal changes in body size and fecundity and to test whether the size scaling of fecundity was isometric (linear) or allometric (curvilinear).ResultsWe show that the total reproductive‐energy output of larger nesting females was, on average, disproportionately greater in all sea turtle species. We found no strong correlations for countries with a higher proportion of protected nesting sites with female size. Finally, we showed that scaling‐derived calculations of population‐level yearly reproductive output in the green turtle population from Redang Island were more accurate when using a hyperallometric (rather than an isometric) relationship at the individual level.Main conclusionsUnderstanding ecosystem function and conservation effort requires accurate predictions of population trends. Our findings highlight the necessity to account for scaling effects of body size in predicting anthropogenically mediated population shifts, and the need to protect large females in order to facilitate effective population replenishment.

Improved multilevel storage capacity in Ge2Sb2Te5-based phase-change memory using a high-aspect-ratio lateral structure

Further improvement of storage density is a key challenge for the application of phase-change memory (PCM) in storage-class memory. However, for PCM, storage density improvements include feature size scaling down and multi-level cell (MLC) operation, potentially causing thermal crosstalk issues and phase separation issues, respectively. To address these challenges, we propose a high-aspect-ratio (25:1) lateral nanowire (NW) PCM device with conventional chalcogenide Ge2Sb2Te5 (GST-225) to realize stable MLC operations, i.e., low intra- and inter-cell variability and low resistance drift (coefficient = 0.009). The improved MLC performance is attributed to the high aspect ratio, which enables precise control of the amorphous region because of sidewall confinement, as confirmed by transmission electron microscopy analysis. In summary, the NW devices provide guidance for the design of future high-aspect-ratio three-dimensional PCM devices with MLC capability.

Novel Diffusion Mechanism of Polymers Pinned to an Attractive Impurity.

Actual substrates unavoidably possess, to some extent, defects and dirt, which motivate understanding the impact due to their presence. The presence of a substrate naturally breaks symmetries. Additionally, it effectively reduces spatial dimensionality, which favors fluctuation-dominated behavior, but it also provides a multitude of possible interactions. We show evidence of novel behavior in the case of polymer mass transport at a crystalline substrate when a single attractive impurity is present. Specifically, we introduce a model system describing how an attractive impurity pins adsorbed polymers on a substrate. We propose a novel mechanism to explain the size scaling dependence of the diffusion coefficient as for polymers with N monomers. Additionally, the size dependence of the diffusion coefficient scales can be described as , with as determined from extensive simulations.

Two-dimensional continuum percolation models with disks under the generalized Achlioptas process

We investigate the disk percolation phase transitions in continuum models in two dimensions under four kinds of generalized product rule and four kinds of generalized sum rule, respectively. We study the critical behaviors of the largest, second largest clusters and their size ratio to characterize the universality class of percolation transition. Using the finite size scaling analysis and the Monte Carlo simulation, we calculate the critical exponents of the percolation transitions under the above rules. We find that the universality classes of continuum percolation under the generalized product rule, under the generalized sum rule, and the lattice percolation are different.