Time-correlation functions for odd Langevin systems.

We investigate the statistical properties of fluctuations in active systems that are governed by nonsymmetric responses. Both an underdamped Langevin system with an odd resistance tensor and an overdamped Langevin system with an odd elastic tensor are studied. For a system in thermal equilibrium, the time-correlation functions should satisfy time-reversal symmetry and the antisymmetric parts of the correlation functions should vanish. For the odd Langevin systems, however, we find that the antisymmetric parts of the time-correlation functions can exist and that they are proportional to either the odd resistance coefficient or the odd elastic constant. This means that the time-reversal invariance of the correlation functions is broken due to the presence of odd responses in active systems. Using the short-time asymptotic expressions of the time-correlation functions, one can estimate an odd elastic constant of an active material such as an enzyme or a motor protein.

Boundary behaviours of Leishmania mexicana: A hydrodynamic simulation study.

It is well established that the parasites of the genus Leishmania exhibit complex surface interactions with the sandfly vector midgut epithelium, but no prior study has considered the details of their hydrodynamics. Here, the boundary behaviours of motile Leishmania mexicana promastigotes are explored in a computational study using the boundary element method, with a model flagellar beating pattern that has been identified from digital videomicroscopy. In particular a simple flagellar kinematics is observed and quantified using image processing and mode identification techniques, suggesting a simple mechanical driver for the Leishmania beat. Phase plane analysis and long-time simulation of a range of Leishmania swimming scenarios demonstrate an absence of stable boundary motility for an idealised model promastigote, with behaviours ranging from boundary capture to deflection into the bulk both with and without surface forces between the swimmer and the boundary. Indeed, the inclusion of a short-range repulsive surface force results in the deflection of all surface-bound promastigotes, suggesting that the documented surface detachment of infective metacyclic promastigotes may be the result of their particular morphology and simple hydrodynamics. Further, simulation elucidates a remarkable morphology-dependent hydrodynamic mechanism of boundary approach, hypothesised to be the cause of the well-established phenomenon of tip-first epithelial attachment of Leishmania promastigotes to the sandfly vector midgut.

Human sperm swimming in a high viscosity mucus analogue.

Remarkably, mammalian sperm maintain a substantive proportion of their progressive swimming speed within highly viscous fluids, including those of the female reproductive tract. Here, we analyse the digital microscopy of a human sperm swimming in a highly viscous, weakly elastic mucus analogue. We exploit principal component analysis to simplify its flagellar beat pattern, from which boundary element calculations are used to determine the time-dependent flow field around the sperm cell. The sperm flow field is further approximated in terms of regularised point forces, and estimates of the mechanical power consumption are determined, for comparison with analogous low viscosity media studies. This highlights extensive differences in the structure of the flows surrounding human sperm in different media, indicating how the cell-cell and cell-boundary hydrodynamic interactions significantly differ with the physical microenvironment. The regularised point force decomposition also provides cell-level information that may ultimately be incorporated into sperm population models. We further observe indications that the core feature in explaining the effectiveness of sperm swimming in high viscosity media is the loss of cell yawing, which is related with a greater density of regularised point force singularities along the axis of symmetry of the flagellar beat to represent the flow field. In turn this implicates a reduction of the wavelength of the distal beat pattern - and hence dynamical wavelength selection of the flagellar beat - as the dominant feature governing the effectiveness of sperm swimming in highly viscous media.

Coarse-Graining the Fluid Flow around a Human Sperm.

The flagellar beat is extracted from human sperm digital imaging microscopy and used to determine the flow around the cell and its trajectory, via boundary element simulation. Comparison of the predicted cell trajectory with observation demonstrates that simulation can predict fine-scale sperm dynamics at the qualitative level. The flow field is also observed to reduce to a time-dependent summation of regularized Stokes flow singularities, approximated at leading order by a blinking force triplet. Such regularized singularity decompositions may be used to upscale cell level detail into population models of human sperm motility.

Hydrodynamic evolution of sperm swimming: Optimal flagella by a genetic algorithm.

Swimming performance of spermatozoa is an important index for the success of fertilization. For many years, numerous studies have reported the optimal swimming of flagellar organisms. Nevertheless, there is still a question as to which is optimal among planar, circular helical and ellipsoidal helical beating. In this paper, we use a genetic algorithm to investigate the beat pattern with the best swimming efficiency based on hydrodynamic dissipation and internal torque exertion. For the parameters considered, our results show that the planar beat is optimal for small heads and the helical flagellum is optimum for a larger heads, while the ellipsoidal beat is never optimal. Also, the genetic optimization reveals that the wavenumber and shape of wave envelope are relevant parameters, whereas the wave shape and head geometry have relatively minor effects on efficiency. The optimal beat with respect to the efficiency based on the internal torque exertion of an active elastic flagellum is characterized by a small-wavenumber and large-amplitude wave in a lower-viscosity medium. The obtained results on the optimal waveform are consistent with observations for planar waveforms, but in many respects, the results suggest the necessity of a detailed flagellar structure-fluid interaction to address whether real spermatozoa exhibit hydrodynamically efficient swimming. The evolutional optimization approach used in this study has distinguished biologically important parameters, and the methodology can potentially be applicable to various swimmers.

A simulation study of sperm motility hydrodynamics near fish eggs and spheres.

For teleost fish fertilisation, sperm must proceed through a small opening on the egg surface, referred to as the micropyle. In this paper, we have used boundary element simulations to explore whether the hydrodynamic attraction between sperm and a fish egg can be a sperm guidance cue. Hydrodynamical egg-sperm interactions alone do not increase the chances of an egg encounter, nor do they induce surface swimming for virtual turbot fish sperm across smooth spheres with a diameter of 1mm, which is representative of a turbot fish egg. When a repulsive surface force between the virtual turbot sperm and the egg is introduced, as motivated by surface charge and van-der-Waals interactions for instance, we find that extended surface swimming of the virtual sperm across a model turbot egg occurs, but ultimately the sperm escapes from the egg. This is due to the small exit angle of the scattering associated with the initial sperm-egg interaction at the egg surface, leading to a weak drift away from the egg, in combination with a weak hydrodynamical attraction between both gametes, though the latter is not sufficient to prevent eventual escape. The resulting transience is not observed experimentally but is a detailed quantitative difference between theory and observation in that stable surface swimming is predicted for eggs with radii larger than about 1.8mm. Regardless, the extended sperm swimming trajectory across the egg constitutes a two-dimensional search for the micropyle and thus the egg is consistently predicted to provide a guidance cue for sperm once they are sufficiently close. In addition, the observation that the virtual turbot sperm swims stably next to a flat plane given repulsive surface interactions, but does not swim stably adjacent to a turbot-sized egg, which is extremely large by sperm-lengthscales, also highlights that the stability of sperm swimming near a boundary is very sensitive to geometry.

A study of spermatozoan swimming stability near a surface.

The swimming stability of spermatozoa with a specified planar beat pattern in the presence of a no-slip flat surface is explored in a modelling study exploiting direct numerical computation via the boundary element method and dynamical systems theory. Parameter sweeps varying the sperm head morphology and flagellar beat pattern wavenumber are conducted and reveal that stable surface swimming is a robust hydrodynamical phenomenon across extensive parameter values, emphasising that diverse sperm will readily swim adjacent to a surface without detailed feedback. There is little sensitivity to the details of the sperm head morphologies considered and, in particular, cells with human sperm head geometries are well approximated by those with prolate ellipsoid heads. However, surface accumulation is predicted to be inhibited by changes associated with mammalian sperm hyperactivation and quantitative aspects, such as the accumulation height associated with surface swimming, are sensitive to the flagellar beat pattern wavenumber and even to the asymptotically small modelling approximations of slender body theory. In particular, the predicted sensitivity of the accumulation height of swimming sperm to the beat pattern wavenumber is sufficient to suggest the possibility that the limited focal depth of typical microscopy studies analysing flagellar patterns with a fixed focal plane may inadvertently bias the wavenumber of the sperm that are observed.

Hybrid motility mechanism of sperm at viscoelastic-solid interface.

To fertilize eggs, sperm must pass through narrow, complex channels filled with viscoelastic fluids in the female reproductive tract. While it is known that the topography of the surfaces plays a role in guiding sperm movement, sperm have been thought of as swimmers, i.e., their motility comes solely from sperm interaction with the surrounding fluid, and therefore, the surfaces have no direct role in the motility mechanism itself. Here, we examined the role of solid surfaces in the movement of sperm in a highly viscoelastic medium. By visualizing the flagellum interaction with surfaces in a microfluidic device, we found that the flagellum stays close to the surface while the kinetic friction between the flagellum and the surface is in the direction of sperm movement, providing thrust. Additionally, the flow field generated by sperm suggests slippage between the viscoelastic fluid and the solid surface, deviating from the no-slip boundary typically used in standard fluid dynamics models. These observations point to hybrid motility mechanisms in sperm involving direct flagellum-surface interaction in addition to flagellum pushing the fluid. This finding signifies an evolutionary strategy of mammalian sperm crucial for their efficient migration through narrow, mucus-filled passages of the female reproductive tract.

Hybrid motility mechanism of sperm at viscoelastic fluid-solid interface.

To fertilize eggs, sperm must pass through narrow, complex channels filled with viscoelastic fluids in the female reproductive tract. While it is known that the topography of the surfaces plays a role in guiding sperm movement, sperm have been thought of as swimmers, i.e., their motility comes solely from sperm interaction with the surrounding fluid, and therefore, the surfaces have no direct role in the motility mechanism itself. Here, we examined the role of solid surfaces in the movement of sperm in a highly viscoelastic medium. By visualizing the flagellum interaction with surfaces in a microfluidic device, we found that the flagellum stays close to the surface while the kinetic friction between the flagellum and the surface is in the direction of sperm movement, providing thrust. Additionally, the flow field generated by sperm suggests slippage between the viscoelastic fluid and the solid surface, deviating from the no-slip boundary typically used in standard fluid dynamics models. These observations point to hybrid motility mechanisms in sperm involving direct flagellum-surface interaction in addition to flagellum pushing the fluid. This finding signifies an evolutionary strategy of mammalian sperm crucial for their efficient migration through narrow, mucus-filled passages of the female reproductive tract.

Squirmer hydrodynamics near a periodic surface topography.

The behaviour of microscopic swimmers has previously been explored near large-scale confining geometries and in the presence of very small-scale surface roughness. Here, we consider an intermediate case of how a simple microswimmer, the tangential spherical squirmer, behaves adjacent to singly and doubly periodic sinusoidal surface topographies that spatially oscillate with an amplitude that is an order of magnitude less than the swimmer size and wavelengths that are also within an order of magnitude of this scale. The nearest neighbour regularised Stokeslet method is used for numerical explorations after validating its accuracy for a spherical tangential squirmer that swims stably near a flat surface. The same squirmer is then introduced to different surface topographies. The key governing factor in the resulting swimming behaviour is the size of the squirmer relative to the surface topography wavelength. For instance, directional guidance is not observed when the squirmer is much larger, or much smaller, than the surface topography wavelength. In contrast, once the squirmer size is on the scale of the topography wavelength, limited guidance is possible, often with local capture in the topography troughs. However, complex dynamics can also emerge, especially when the initial configuration is not close to alignment along topography troughs or above topography crests. In contrast to sensitivity in alignment and topography wavelength, reductions in the amplitude of the surface topography or variations in the shape of the periodic surface topography do not have extensive impacts on the squirmer behaviour. Our findings more generally highlight that the numerical framework provides an essential basis to elucidate how swimmers may be guided by surface topography.

Massive bleeding from a duodenal ulcer in a child with influenza infection: A case report of endoscopic findings.

Gastrointestinal bleeding or perforation following influenza infection is rare. We encountered a pediatric case of hemorrhagic duodenal ulcer following influenza A infection. The patient was a 1-year and 4-month-old boy who was diagnosed with influenza A infection and treated with laninamivir octanoate. After inhalation, he had diarrhea, poor appetite, and melena. The next day, he had hematochezia and developed hemorrhagic shock. Contrast-enhanced computed tomography showed extravasation in the descending part of the duodenum. Esophagogastroduodenoscopy revealed spurting bleeding from a Dieulafoy's lesion on the oral side of the major papilla, and he underwent hemostasis by clipping. From the bulb to the descending part of the duodenum, the mucosa appeared atrophic with spotty redness on the circular folds and multiple and irregularly shaped erosions. Almost all mucosal lesions had healed by the eighth day, and he was monitored as an outpatient for more than one year without re-bleeding. Intestinal ischemia, viral invasion, and drug reaction of laninamivir octanoate may be involved in duodenal mucosal injury. Acute duodenal ulcers may occur in children with influenza infection, especially young children.

Most probable path of an active Brownian particle.

In this study, we investigate the transition path of a free active Brownian particle (ABP) on a two-dimensional plane between two given states. The extremum conditions for the most probable path connecting the two states are derived using the Onsager-Machlup integral and its variational principle. We provide explicit solutions to these extremum conditions and demonstrate their nonuniqueness through an analogy with the pendulum equation indicating possible multiple paths. The pendulum analogy is also employed to characterize the shape of the globally most probable path obtained by explicitly calculating the path probability for multiple solutions. We comprehensively examine a translation process of an ABP to the front as a prototypical example. Interestingly, the numerical and theoretical analyses reveal that the shape of the most probable path changes from an I to a U shape and to the ℓ shape with an increase in the transition process time. The Langevin simulation also confirms this shape transition. We also discuss further method applications for evaluating a transition path in rare events in active matter.

Self-organized swimming with odd elasticity.

We theoretically investigate self-oscillating waves of an active material, which were recently introduced as a nonsymmetric part of the elastic moduli, termed odd elasticity. Using Purcell's three-link swimmer model, we reveal that an odd-elastic filament at low Reynolds number can swim in a self-organized manner and that the time-periodic dynamics are characterized by a stable limit cycle generated by elastohydrodynamic interactions. Also, we consider a noisy shape gait and derive a swimming formula for a general elastic material in the Stokes regime with its elasticity modulus being represented by a nonsymmetric matrix, demonstrating that the odd elasticity produces biased net locomotion from random noise.

High insertion of the right diaphragm complicated with congenital diaphragmatic hernia: A case report of rare thoracoscopic findings.

We encountered a case of high insertion of the right diaphragm complicated with congenital diaphragmatic hernia that was diagnosed based on thoracoscopic findings. A full-term male baby was suspected of having right congenital diaphragmatic hernia or diaphragmatic eventration on postnatal imaging. He only had episodes of mild but prolonged symptoms following upper respiratory tract infection and his course was otherwise uneventful during outpatient monitoring. At 1 year old, the elevated liver volume remained large, which might eventually interfere with his lung growth, so thoracoscopic exploration was planned. Thoracoscopy revealed liver prolapse from a diaphragmatic defect. In addition, the anterior to lateral inserted part of the diaphragm was high, with the anterior part reaching the fourth rib. We repaired only the diaphragmatic defect without repositioning the diaphragm, and the postoperative course was uneventful. High insertion of the diaphragm should be considered as a differential diagnosis of congenital diaphragmatic eventration.

Tissue flow regulates planar cell polarity independently of the Frizzled core pathway.

Planar cell polarity (PCP) regulates the orientation of external structures. A core group of proteins that includes Frizzled forms the heart of the PCP regulatory system. Other PCP mechanisms that are independent of the core group likely exist, but their underlying mechanisms are elusive. Here, we show that tissue flow is a mechanism governing core group-independent PCP on the Drosophila notum. Loss of core group function only slightly affects bristle orientation in the adult central notum. This near-normal PCP results from tissue flow-mediated rescue of random bristle orientation during the pupal stage. Manipulation studies suggest that tissue flow can orient bristles in the opposite direction to the flow. This process is independent of the core group and implies that the apical extracellular matrix functions like a "comb" to align bristles. Our results reveal the significance of cooperation between tissue dynamics and extracellular substances in PCP establishment.

Driving a Microswimmer with Wall-Induced Flow.

Active walls such as cilia and bacteria carpets generate background flows that can influence the trajectories of microswimmers moving nearby. Recent advances in artificial magnetic cilia carpets offer the potentiality to use a similar wall-generated background flow to steer bio-hybrid microrobots. In this paper, we provide some ground theoretical and numerical work assessing the viability of this novel means of swimmer guidance by setting up a simple model of a spherical swimmer in an oscillatory flow and analysing it from the control theory viewpoint. We show a property of local controllability around the reference free trajectories and investigate the bang-bang structure of the control for time-optimal trajectories, with an estimation of the minimal time for suitable objectives. By direct simulation, we have demonstrated that the wall actuation can improve the wall-following transport by nearly 50%, which can be interpreted by synchronous flow structure. Although an open-loop control with a periodic bang-bang actuation loses some robustness and effectiveness, a feedback control is found to improve its robustness and effective transport, even with hydrodynamic wall-swimmer interactions. The results shed light on the potentialities of flow control and open the way to future experiments on swimmer guidance.

Modelling Motility: The Mathematics of Spermatozoa.

In one of the first examples of how mechanics can inform axonemal mechanism, Machin's study in the 1950s highlighted that observations of sperm motility cannot be explained by molecular motors in the cell membrane, but would instead require motors distributed along the flagellum. Ever since, mechanics and hydrodynamics have been recognised as important in explaining the dynamics, regulation, and guidance of sperm. More recently, the digitisation of sperm videomicroscopy, coupled with numerous modelling and methodological advances, has been bringing forth a new era of scientific discovery in this field. In this review, we survey these advances before highlighting the opportunities that have been generated for both recent research and the development of further open questions, in terms of the detailed characterisation of the sperm flagellum beat and its mechanics, together with the associated impact on cell behaviour. In particular, diverse examples are explored within this theme, ranging from how collective behaviours emerge from individual cell responses, including how these responses are impacted by the local microenvironment, to the integration of separate advances in the fields of flagellar analysis and flagellar mechanics.

Control and controllability of microswimmers by a shearing flow.

With the continuing rapid development of artificial microrobots and active particles, questions of microswimmer guidance and control are becoming ever more relevant and prevalent. In both the applications and theoretical study of such microscale swimmers, control is often mediated by an engineered property of the swimmer, such as in the case of magnetically propelled microrobots. In this work, we will consider a modality of control that is applicable in more generality, effecting guidance via modulation of a background fluid flow. Here, considering a model swimmer in a commonplace flow and simple geometry, we analyse and subsequently establish the efficacy of flow-mediated microswimmer positional control, later touching upon a question of optimal control. Moving beyond idealized notions of controllability and towards considerations of practical utility, we then evaluate the robustness of this control modality to sources of variation that may be present in applications, examining in particular the effects of measurement inaccuracy and rotational noise. This exploration gives rise to a number of cautionary observations, which, overall, demonstrate the need for the careful assessment of both policy and behavioural robustness when designing control schemes for use in practice.

Computer-assisted beat-pattern analysis and the flagellar waveforms of bovine spermatozoa.

Obstructed by hurdles in information extraction, handling and processing, computer-assisted sperm analysis systems have typically not considered in detail the complex flagellar waveforms of spermatozoa, despite their defining role in cell motility. Recent developments in imaging techniques and data processing have produced significantly improved methods of waveform digitization. Here, we use these improvements to demonstrate that near-complete flagellar capture is realizable on the scale of hundreds of cells, and, further, that meaningful statistical comparisons of flagellar waveforms may be readily performed with widely available tools. Representing the advent of high-fidelity computer-assisted beat-pattern analysis, we show how such a statistical approach can distinguish between samples using complex flagellar beating patterns rather than crude summary statistics. Dimensionality-reduction techniques applied to entire samples also reveal qualitatively distinct components of the beat, and a novel data-driven methodology for the generation of representative synthetic waveform data is proposed.

The N-flagella problem: elastohydrodynamic motility transition of multi-flagellated bacteria.

Peritrichous bacteria such as Escherichia coli swim in viscous fluids by forming a helical bundle of flagellar filaments. The filaments are spatially distributed around the cell body to which they are connected via a flexible hook. To understand how the swimming direction of the cell is determined, we theoretically investigate the elastohydrodynamic motility problem of a multi-flagellated bacterium. Specifically, we consider a spherical cell body with a number N of flagella which are initially symmetrically arranged in a plane in order to provide an equilibrium state. We solve the linear stability problem analytically and find that at most six modes can be unstable and that these correspond to the degrees of freedom for the rigid-body motion of the cell body. Although there exists a rotation-dominated mode that generates negligible locomotion, we show that for the typical morphological parameters of bacteria the most unstable mode results in linear swimming in one direction accompanied by rotation around the same axis, as observed experimentally.