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During development, cells sequentially lose their ability to differentiate into other cell types and become committed to different cellular states. This process can be described as a landscape in which the valleys are canalized one by one. This process of canalization is understood in terms of dynamical systems of interacting cells. In fact, as cells with oscillating gene expression proliferate and interact with each other, they differentiate into other expression states. Cells with oscillatory gene expression have pluripotency, either to replicate the same state or to differentiate into other cellular states, whereas cells that differentiate and lose their oscillations of expression simply replicate themselves, that is, they are committed. The proportion of each cell type is robust to changes in initial conditions and noise perturbations. Differentiation by protein expression dynamics is further stabilized by a feedback process of epigenetic modifications, such as DNA modification. The irreversibly differentiated cell state can be initialized to a pluripotent state by restoring an oscillatory state by forcing the expression of multiple genes from the outside, known experimentally as reprogramming.
Oscillator circuits, categorized into relaxation and sinusoidal types, are introduced. Three examples of relaxation oscillators are given and analyzed: the SCR sawtooth, the transistor astable, and the 555 astable. Monostable operation of the 555 timer is also discussed. For sinusoidal oscillators, examples include a transistor RC, an op-amp Wien bridge, a Hartley, and a Pierce oscillator. Oscillator stability is discussed. Electromagnetic communications (AM and FM) are discussed as applications of oscillators.
Capacitors and inductors are introduced, along with their equivalent circuit laws. Switched RC circuits are thoroughly analyzed. The response of an RC circuit to a sinusoidal drive voltage is analyzed and leads to a discussion of high- and low-pass filters, phase shifters, integrators, and differentiators. The use of complex numbers in circuit analysis is introduced and applied to sinusoidally driven series RC, LR, and LRC circuits as well as the switched LRC circuit. Fourier analysis and its meaning are presented. The operation of transformers is introduced.
This chapter presents an overview of the goals of universal biology. It is noted that biological systems are generally hierarchical as molecules-cells-organisms, where the components of each level are quite diverse. How such diversity arises and is maintained is discussed. We then discuss the possibility of understanding such biological systems with diverse components, and explore the possibility of macroscopic theory to reveal and formulate universal properties in living states, noting that robustness, plasticity, and activity are essential to life. Recalling the spirit (not the formulation) of thermodynamics, we explore the possibility of formulating a theory for characterizing universal properties in life, emphasizing macroscopic robustness at each level of the hierarchy and the importance of macro-micro consistency.
Cells reproduce under nonequilibrium conditions. By noting that a cell contains enzymes that drastically increase the equilibration process, it is shown that a cell is an apparatus that reveals the nonequilibrium property of the environment and accelerates equilibration. As a consequence, the entropy generation rate per cell growth is minimized at a finite growth rate, not in the adiabatic limit as in the Carnot cycle. General statistical properties of cells are then presented, including the power law in abundances and the lognormal distribution of cell-to-cell variation. The transition from exponential growth to the dormant state (where cell growth is arrested) is shown to be a general consequence of the accumulation of waste (non-autocatalytic) components, which leads to a jamming of the reaction. Related experiments using single-cell measurements elucidate the distribution of cell-to-cell variation in protein concentrations and growth rates. How cell reproduction and molecular replication achieve consistency is also a fundamental question for constructing protocells and understanding the origin of life. The relationship between minority molecules and genetic information, the synchronization of minority molecular replication and cell division, the separation of genetic information and catalytic function, and the acquisition of evolutionary potential are discussed as universal properties that must be satisfied for all cell reproduction systems.
Consider the evolutionary process under fixed environmental conditions, where genetic change leads to phenotypic change, and fitness is given as a function of phenotype. In this case, the variance Vip of the fluctuation of the phenotype due to noise is proportional to the rate of evolution of the phenotype, termed as evolutionary fluctuation–response relationship. It then implies that Vip is proportional to Vg, the variance due to genetic variation, as derived theoretically under the assumption of evolutionary robustness: the acquisition of phenotypic robustness to noise through evolution also leads to robustness to genetic variation. Here, as the mutation rate increases (or the noise level in the dynamics decreases), a phenotypic error catastrophe occurs, where it is no longer possible to maintain the fit phenotype. While phenotypic variance and evolvability decrease under fixed environmental and fitness conditions, they rise and fall repeatedly as environmental conditions are varied over generations. Phenotypic plasticity and evolvability are maintained under environmental variation. Strong selection under fixed evolutionary conditions can lead to the appearance of mutants with increased phenotypic variance. This may be due to over-optimization to obtain the fit phenotype, which may break consistency with other processes and reduce robustness.
The conventional $\textrm{e}^N$ laminar-to-turbulent transition-prediction method focuses on the relative growth rate, called the $N$ factor, and neglects receptivity. To improve predictions, Mack (1977) proposed the amplitude method to incorporate receptivity, nonlinear effects and broadband characteristics. Currently, the lack of accurate receptivity coefficients, estimates of initial disturbance amplitudes at the lower-branch neutral position, referred to as branch I (where the imaginary part of the spatial wavenumber is zero), hinders the application of the amplitude method. Although experimental- and numerical-receptivity analyses have been conducted previously, they rely on correlations or indirect approaches. For the purpose of direct evaluation, this study applies bi-orthogonal decomposition to direct numerical simulation (DNS) data of a hypersonic boundary layer over a blunt cone, extracting initial amplitudes of instability modes. The decomposition framework incorporates both boundary-layer and entropy-layer modes, enabling direct evaluation of receptivity coefficients at branch I. The decomposed modal amplitudes show reduced multimode interference and the receptivity coefficients have been computed to have fewer oscillations. With an overall greater magnitude, the receptivity coefficients suggest a possible earlier transition location than the previous numerical study by He & Zhong (2023 J. Spacecr. Rockets, vol. 60, no. 6, pp. 1927–1938). Additionally, a discrete entropy-layer mode is recovered, contributing to instability development alongside modes F and S. These findings support the use of bi-orthogonal decomposition as a practical tool for receptivity analysis and enhancement of the amplitude method in transition prediction.
The nonlinear growth of perturbations in hydrodynamic interfacial instabilities can be of particular importance in both scientific research (e.g. supernova explosion) and engineering applications (e.g. inertial confinement fusion). One of the most significant issues in these instabilities is the long-time nonlinear bubble evolution of a single-mode Rayleigh–Taylor instability (RTI), which remains as an unsolved and challenging problem since Taylor’s seminal work more than seven decades ago. Introduced in this paper is an analytical model for the long-time evolution of bubble velocity, curvature and vorticity, which is established by considering the vorticity accumulation around the bubble in a bilaterally rotational flow system under the classical planar potential-flow theory framework. The proposed theoretical model incorporates not only the classical linear, nonlinear and quasi-steady stages, but the late re-acceleration stage. Meanwhile, the new model can capture the phenomenon of secondary velocity saturation following the stage of bubble re-acceleration. The good agreement between the present model and numerical simulations for all density ratios and dimensions confirms that the accumulation in vorticity tends to break the early stage buoyancy-drag equilibrium mechanism and leads to the establishment of a new equilibrium in the late-stage RTI.
Asymmetries and anisotropies are widespread in biological systems, including in the structure and dynamics of cilia and eukaryotic flagella. These microscopic, hair-like appendages exhibit asymmetric beating patterns that break time-reversal symmetry needed to facilitate fluid transport at the cellular level. The intrinsic anisotropies in ciliary structure can promote preferential beating directions, further influencing their dynamics. In this study, we employ numerical simulation and bifurcation analysis of a mathematical model of a filament driven by a follower force at its tip to explore how intrinsic curvature and direction-dependent bending stiffnesses impact filament dynamics. Our results show that while intrinsic curvature is indeed able to induce asymmetric beating patterns when filament motion is restricted to a plane, this beating is unstable to out-of-plane perturbations. Furthermore, we find that a three-dimensional whirling state seen for isotropic filament dynamics can be suppressed when sufficient asymmetry or anisotropy are introduced. Finally, for bending stiffness ratios as low as 2, we demonstrate that combining structural anisotropy with intrinsic curvature can stabilise asymmetric beating patterns, highlighting the crucial role of anisotropy in ciliary dynamics.
The motionless conducting state of liquid-metal convection with an applied vertical magnetic field confined in a vessel with insulating sidewalls becomes linearly unstable to wall modes through a supercritical pitchfork bifurcation. Nevertheless, we show that the transition proceeds subcritically, with stable finite-amplitude solutions with different symmetries existing at parameter values beneath this linear stability threshold. Under increased thermal driving, the branch born from the linear instability becomes unstable and solutions are attracted to the most subcritical branch, which follows a quasiperiodic route to chaos. Thus, we show that the transition to turbulence is controlled by this subcritical branch and hence turbulent solutions have no connection to the initial linear instability. This is further quantified by observing that the subcritical equilibrium solution sets the spatial symmetry of the turbulent mean flow and thus organises large-scale structures in the turbulent regime.
Post-asymptotic giant branch (post-AGB) binary stars are evolved systems that host circumbinary discs formed through mass loss during late stage binary interactions. Their structural, morphological, kinematic, and chemical similarities to planet-forming discs suggest that these systems may act as sites of ‘second-generation’ planet formation. In this study, we assess whether the disc instability mechanism – a proposed pathway for rapid, giant planet formation in some protoplanetary discs - can operate in post-AGB discs; motivated by their short lifetimes ($10^{4-5}$ yr). Using the Toomre criterion under well motivated assumptions for disc structure and size, mass, and thermal properties, we assess the conditions for gravitational instability. We first benchmark our analytical framework using well studied protoplanetary disc systems (including HL Tauri, Elias 2-27, GQ Lupi) before applying the same analysis to observed post-AGB discs. We find that post-AGB discs are generally gravitationally stable at present, due primarily to their low masses. Using viscous disc theory, we find that the discs were stable against collapse even in the past, when their masses were potentially higher. In contrast, several protoplanetary discs analysed in the same way show that they likely experienced gravitationally unstable phases early on. We also find that higher viscosity parameters ($\alpha \sim 10^{-2}$) are better aligned with expected post-AGB disc lifetimes. Finally, we revisit the planet formation scenario proposed for the post-common envelope system NN Ser, first carried out by Schleicher and Dreizler, and we show that gravitational instability could be feasible under specific, high disc mass assumptions. Overall, our results provide the first systematic theoretical assessment of gravitational instability in post-AGB discs, demonstrating that this mechanism is unlikely to dominate second-generation planet formation in these systems and underscoring the need to explore alternative pathways – such as core accretion – in future studies.
Internal waves in a two-layer fluid with rotation are considered within the framework of Helfrich’s $f$-plane extension of the Miyata–Maltseva–Choi–Camassa model. We develop simultaneous asymptotic expansions for the evolving mean fields and deviations from them to describe a large class of uni-directional waves via the Ostrovsky equation, which fully decouples from mean-field variations. The latter generate additive inertial oscillations in the shear and in the phase of both the interfacial displacement and shear. Unlike conventional derivations leading to the Ostrovsky equation, our formulation does not impose the zero-mean constraints on the initial conditions of any variable. Using the constructed solutions, we model the evolution of quasi-periodic initial conditions close to the cnoidal wave solutions of the Korteweg–de Vries (KdV) equation but with local defects, both with and without rotation. We show that rotation leads to the emergence of bursts of internal waves and shear currents, qualitatively similar to the wavepackets generated from solitons and modulated cnoidal waves in earlier studies, but emerging much faster. We also show that cnoidal waves with expansion defects discussed in this work are generalised travelling waves of the KdV equation: they satisfy all conservation laws of the KdV equation (appropriately understood), as well as the Weirstrass–Erdmann corner condition for broken extremals of the associated variational problem and a natural weak formulation. Being smoothed in numerical simulations, they behave, in the absence of rotation, as long-lived states with no visible evolution, while rotation leads to the emergence of strong bursts.
We study the stability of a steady Eckart streaming jet flowing in a closed cylindrical cavity. This configuration is a generic representation of industrial processes where driving flows in a cavity by means of acoustic forcing offers a contactless way of stirring or controlling flows. Successfully doing so, however, requires sufficient insight into the topology induced by the acoustic beam. This, in turn, raises the more fundamental question of whether the basic jet topology is stable and, when it is not, of the alternative states that end up being acoustically forced. To answer these questions, we consider a flow forced by an axisymmetric diffracting beam of attenuated sound waves emitted by a plane circular transducer at one cavity end. At the opposite end, the jet impingement drives recirculating structures spanning nearly the entire cavity radius. We rely on linear stability analysis (LSA) together with three-dimensional nonlinear simulations to identify the flow destabilisation mechanisms and to determine the bifurcation criticalities. We show that flow destabilisation is closely related to the impingement-driven recirculating structures, and that the ratio $C_R$ between the cavity and the maximum beam radii plays a key role on the flow stability. In total, we identified four mode types destabilising the flow. For $4 \leqslant C_R \leqslant 6$, a non-oscillatory perturbation rooted in the jet impingement triggers a supercritical bifurcation. For $C_R = 3$, the flow destabilises through a subcritical non-oscillatory bifurcation and we explain the topological change of the unstable perturbation by analysing its critical points. Further reducing $C_R$ increases the shear within the flow and gradually moves the instability origin to the shear layer between impingement-induced vortices: for $C_R = 2$, an unstable travelling wave grows out of a subcritical bifurcation, which becomes supercritical for $C_R=1$. For each geometry, the nonlinear three-dimensional (3-D) simulations confirm both the topology and the growth rate of the unstable perturbation returned by LSA. This study offers fundamental insight into the stability of acoustically driven flows in general, but also opens possible pathways to either induce turbulence acoustically or to avoid it in realistic configurations.
With the growing number of gravitational wave detections, achieving a competitive measurement of $H_0$ with dark sirens is becoming increasingly feasible. The expansion of the LIGO-Virgo-KAGRA Collaboration into a four detector network will reduce both the localisation area and the luminosity distance uncertainty associated with each gravitational wave event. It is therefore essential to identify and mitigate other major sources of error that could increase the uncertainty in $H_0$. In this work, we explore three scenarios relevant to the dark siren method in future observing runs. First, we demonstrate that there is a precision gain offered by a catalogue of spectroscopic-like redshifts compared to photometric-like redshifts, with the greatest improvements observed in smaller localisation areas. Second, we show that redshift outliers (as occur in realistic photometric redshift catalogues), do not introduce bias into the measurement of $H_0$. Finally, we find that uniformly sub-sampling spectroscopic-like redshift catalogues increases the uncertainty in $H_0$ as the completeness fraction is decreased; at a completeness of 50% the benefit of spectroscopic redshift precision is outweighed by the degradation from incompleteness. In all three scenarios, we obtain unbiased estimates of $H_0$. We conclude that a competitive measurement of $H_0$ using the dark siren method will require a hybrid catalogue of both photometric and spectroscopic redshifts, at least until highly complete spectroscopic catalogues become available. This, however, will come at the cost of a more complex selection function.
In 2019, in this journal, I discussed approaches for controlling the movement of molecules, in particular macromolecules, with an emphasis on how this enabled advances in the field of drug delivery – a field that has impacted billions of people worldwide. Since 2019, there have been advances in our work and this field including a striking demonstration in which drug delivery nanoparticles were crucial to the success of mRNA therapies and the Covid-19 vaccine. In this paper, I provide updates in such areas as i) developing new methods for oral drug delivery systems, ii) delivery of molecules to specific sites of the body, iii) new types of delivery systems, and iv) examples of machine learning/artificial intelligence in these areas. I also discuss advances in mRNA technology as it relates to drug delivery and the development of nanoparticles to protect and deliver vaccines, which saved and improved the lives of hundreds of millions of people throughout the world.
Allosteric communication is established by networks through which strain energy generated at the allosteric site by an allosteric event, such as ligand binding, can propagate to the functional site. Exerted on multiple molecules in the cell, it can wield a biased function. Here, we discuss allosteric networks and allosteric signaling bias. Networks are graphs specified by nodes (residues) and edges (their connections). Allosteric bias is a property of a population. It is described by allosteric effector-specific dynamic distributions of conformational ensembles, as classically exemplified by G protein-coupled receptors (GPCRs). An ensemble describes the likelihood of a specific (strong/weak) allosteric signal propagating to a specific functional site. A network description provides the propagation route in a specific conformation, pinpointing key residues whose mutations could promote drug resistance. Efficiency is influenced by path length, relative stabilities and allosteric transitions. Through specific contacts, specific ligands can bias signaling in proteins, for example, in receptor tyrosine kinases (RTKs) toward specific phosphorylation sites and cell signaling activation. Thus, rather than the two – active and inactive – states, and a single pathway, we consider multiple states and favored pathways. This allows us to consider biased allosteric switches among minor, invisible states and observable outcomes. Within this framework, we further consider signaling strength and duration as key determinants of cell fate: If weak and sustained, it may induce differentiation; If bursts of strong and short, proliferation.
We probe the atomic hydrogen (Hi) emission from the host galaxies of fast radio bursts (FRBs) to investigate the emerging trend of disturbance and asymmetry in the population. Quadrupling the sample size, we detect 16 out of 17 new hosts in Hi, with the single non-detection arising in a galaxy known to be transitioning towards quiescence. With respect to typical local Universe galaxies, FRB hosts are generally massive in Hi ($\gt10^9$ M$_{{\odot}}$), which aligns with previous studies reporting that FRB hosts also tend to have high stellar masses and are star-forming. However, they span a broad range of other Hi derived properties. Using visual inspection alongside various asymmetry metrics, we identify six unambiguously settled host galaxies, demonstrating for the first time that a disturbed Hi morphology is not a universal feature of FRB host galaxies. However, we find another six that show clear signs of disturbance, one borderline case, and three which require deeper or more targeted observations to reach a conclusion; this brings the confirmed ratio of disturbed-to-settled FRB hosts to 11:6. Given that roughly a 1:1 ratio is expected for random background galaxies of similar type, our observed ratio yields a p-value of 0.222. Therefore, we conclude that contrary to earlier indications, there is no statistically significant excess of Hi disturbance in this sample of FRB host galaxies with respect to the general galaxy population, and hence we find no evidence for a fundamental connection between FRB progenitor formation and merger-induced star formation activity.
We use scanning-tomographic particle image velocimetry introduced by Casey, Sakakibara & Thoroddsen (Phys. Fluids, vol. 25 (2), 2013, p. 025102) to measure the volumetric velocity field in a fully turbulent round jet. The experiments are performed for ${Re}=2640,\, 5280$ and $10\,700.$ Using Fourier-based proper orthogonal decomposition (POD), the dominant modes that describe the velocity and vorticity fields are extracted. We employ a new method of averaging POD modes from different experimental runs using a phase-synchronisation with respect to a common basis. For the dominant azimuthal wavenumber $m=1,$ the first and second POD modes of the axial velocity have opposite signs and appear as embracing helical structures, with opposite twist, while, for the same parameters, POD modes of the radial velocity extend to the axis of symmetry and, interestingly, also show a helical shape. The $(m=1)$-POD modes for the azimuthal vorticity appear as two separate structures, consisting of C-shaped loops in the region away from the axis and helically twisted axial tubes close to the axis. The corresponding axial vorticity modes are cone-like and appear as inclined streaks of alternate sign in the $r$–$z$-plane, similar to velocity streaks seen in wall-bounded shear flows. Temporal analysis of the dynamics shows that a $(m=1)$ two-mode velocity POD representation precesses with a Strouhal number of approximately $St=0.05,$ while the same reconstruction based on vorticity POD modes has a slightly higher Strouhal number of $St=0.06.$