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A Jump Distance-based Bayesian analysis method to unveil fine single molecule transport features

Single-molecule tracking (SMT) methods are under considerable expansion in many fields of cell biology, as the dynamics of cellular components in biological mechanisms becomes increasingly relevant. Despite the development of SMT technologies, it is still difficult to reconcile a sparse signal at all times (required to distinguish single molecules) with long individual trajectories, within confined regions of the cell and given experimental limitations. This strongly reduces the performance of current data analysis methods in extracting meaningful transport features from single molecules trajectories. In this work, we develop and implement a new mathematical analysis method of SMT data, which takes advantage of the large number of (short) trajectories that are typically obtained with cellular systems in vivo. The method is based on the fitting of the jump distance distribution, e.g. the distribution that represents how far molecules travel in a set time interval; it uses a Bayesian approach to compare plausible molecule motion models and extract both qualitative and quantitative information. Finally, the method is tested on in silico trajectories simulated using Monte Carlo algorithms, and ranges of parameters for which the method yields accurate results are determined.

q-bio.QM↗

Power law rheology of generalised Maxwell and Kelvin-Voigt models

We analyse the rheological behaviour of the generalised Maxwell and Kelvin-Voigt models with a power law spectrum of relaxation or retardation times, ${\cal H}\sim 1/τ^α$ or ${\cal L}\sim τ^α$, respectively. When $0<α<1$, both models have the same weak power law behaviour, which occur in a variety of soft materials, including living cells. Beyond this region, for other values of $α$, the two models have different and distinctive rheological behaviours, converging continuously to the 1-element Maxwell and Kelvin-Voigt models, respectively, for $α<-1$ or $α>2$.

physics.bio-ph↗

The order-disorder transition in model lipid bilayers is a first-order hexatic to liquid phase transition

We characterize the order-disorder transition in a model lipid bilayer using molecular dynamics simulations. We find that the ordered phase is hexatic. In particular, in-plane structures possess a finite concentration of 5-7 disclination pairs that diffuse throughout the plane of the bilayer, and further, in-plane structures exhibit long-range orientational order and short-range translational order. In contrast, the disordered phase is liquid. The transition between the two phases is first order. Specifically, it exhibits hysteresis, and coexistence exhibits an interface with capillary scaling. The location of the interface and its spatial fluctuations are analyzed with a spatial field constructed from a rotational-invariant for local 6-fold orientational order. As a result of finite interfacial tension, there necessarily exist associated forces of assembly between membrane-bound solutes that pre-melt the ordered phase.

cond-mat.soft↗

Application of the reciprocity theorem to EEG inversion and optimization of EEG-driven transcranial current stimulation (tCS, including tDCS, tACS, tRNS)

Multichannel transcranial current stimulation (tCS) systems offer the possibility of EEG-guided optimized, non-invasive brain stimulation. In this brief technical note I explain how it is possible to use tCS electric field realistic brain model to create a forward "lead-field" matrix and, from that, an EEG inverter for cortical mapping. Starting from EEG I show how to generate 2D cortical surface dipole fields that could produce the observed EEG electrode voltages. The main tool is the reciprocity theorem derived by Helmholtz. The application of reciprocity for the generation of a forward mapping matrix (lead field matrix as is sometimes known) is well known [Rush and Driscoll, 1969], but here we will use it in combination with the realistic head models of [Miranda et al 2013] to provide cortical mapping solutions compatible with realistic head model tCS optimization. I also provide a generalization of the reciprocity theorem [Helmholtz 1853] to the case of multiple electrode contact points and dipole sources, and discuss its uses in non-invasive brain stimulation based on EEG. This, as far as I know, is a novel result. Applications are discussed.

physics.bio-ph↗

Alterations in cell surface area and deformability of individual human red blood cells in stored blood

The functionality and viability of stored human red blood cells (RBCs) is an important clinical issue in transfusion. To systematically investigate changes in stored whole blood, the hematological properties of individual RBCs were quantified in blood samples stored for various periods with and without a preservation solution called CPDA-1. With 3-D quantitative phase imaging techniques, the optical measurements of the 3-D refractive index (RI) distributions and membrane fluctuations were done at the individual cell level. From the optical measurements, the morphological (volume, surface area and sphericity), biochemical (hemoglobin content and concentration), and mechanical parameters (dynamic membrane fluctuation) were simultaneously quantified to investigate the functionalities and their progressive alterations in stored RBCs. Our results show that the stored RBCs without CPDA-1 had a dramatic morphological transformation from discocytes to spherocytes within 2 weeks which was accompanied with significant decreases in cell deformability and cell surface area, and increases in sphericity. However, the stored RBCs with CPDA-1 maintained their morphology and deformability for up to 6 weeks.

physics.med-ph↗

Quantum trajectory tests of radical-pair quantum dynamics in CIDNP measurements of photosynthetic reaction centers

Chemically induced dynamic nuclear polarization is a ubiquitous phenomenon in photosynthetic reaction centers. The relevant nuclear spin observables are a direct manifestation of the radical-pair mechanism. We here use quantum trajectories to describe the time evolution of radical-pairs, and compare their prediction of nuclear spin observables to the one derived from the radical-pair master equation. While our approach provides a consistent description, we unravel a major inconsistency within the conven- tional theory, thus challenging the theoretical interpretation of numerous CIDNP experiments sensitive to radical-pair reaction kinetics.

physics.chem-ph↗

The Theory of Diffraction Tomography

Tomography is the three-dimensional reconstruction of an object from images taken at different angles. The term classical tomography is used, when the imaging beam travels in straight lines through the object. This assumption is valid for light with short wavelengths, for example in x-ray tomography. For classical tomography, a commonly used reconstruction method is the filtered back-projection algorithm which yields fast and stable object reconstructions. In the context of single-cell imaging, the back-projection algorithm has been used to investigate the cell structure or to quantify the refractive index distribution within single cells using light from the visible spectrum. Nevertheless, these approaches, commonly summarized as optical projection tomography, do not take into account diffraction. Diffraction tomography with the Rytov approximation resolves this issue. The explicit incorporation of the wave nature of light results in an enhanced reconstruction of the object's refractive index distribution. Here, we present a full literature review of diffraction tomography. We derive the theory starting from the wave equation and discuss its validity with the focus on applications for refractive index tomography. Furthermore, we derive the back-propagation algorithm, the diffraction-tomographic pendant to the back-projection algorithm, and describe its implementation in three dimensions. Finally, we showcase the application of the back-propagation algorithm to computer-generated scattering data. This review unifies the different notations in literature and gives a detailed description of the back-propagation algorithm, serving as a reliable basis for future work in the field of diffraction tomography.

q-bio.QM↗

3D super-resolved in vitro multiphoton microscopy by saturation of excitation

We demonstrate a significant resolution enhancement beyond the conventional limit in multiphoton microscopy (MPM) using saturated excitation of fluorescence. Our technique achieves super-resolved imaging by temporally modulating the excitation laser-intensity and demodulating the higher harmonics from the saturated fluorescence signal. The improvement of the lateral and axial resolutions is measured on a sample of fluorescent microspheres. While the third harmonic already provides an enhanced resolution, we show that a further improvement can be obtained with an appropriate linear combination of the demodulated harmonics. Finally, we present in vitro imaging of fluorescent microspheres incorporated in HeLa cells to show that this technique performs well in biological samples.

physics.med-ph↗

Reactive Boundary Conditions as Limits of Interaction Potentials for Brownian and Langevin Dynamics

A popular approach to modeling bimolecular reactions between diffusing molecules is through the use of reactive boundary conditions. One common model is the Smoluchowski partial absorption condition, which uses a Robin boundary condition in the separation coordinate between two possible reactants. This boundary condition can be interpreted as an idealization of a reactive interaction potential model, in which a potential barrier must be surmounted before reactions can occur. In this work we show how the reactive boundary condition arises as the limit of an interaction potential encoding a steep barrier within a shrinking region in the particle separation, where molecules react instantly upon reaching the peak of the barrier. The limiting boundary condition is derived by the method of matched asymptotic expansions, and shown to depend critically on the relative rate of increase of the barrier height as the width of the potential is decreased. Limiting boundary conditions for the same interaction potential in both the overdamped Fokker-Planck equation (Brownian Dynamics), and the Kramers equation (Langevin Dynamics) are investigated. It is shown that different scalings are required in the two models to recover reactive boundary conditions that are consistent in the high friction limit where the Kramers equation solution converges to the solution of the Fokker-Planck equation.

physics.bio-ph↗

The geometry of coexistence in large ecosystems

The role of species interactions in controlling the interplay between the stability of an ecosystem and its biodiversity is still not well understood. The ability of ecological communities to recover after a small perturbation of the species abundances (local asymptotic stability) has been well studied, whereas the likelihood of a community to persist when the interactions are altered (structural stability) has received much less attention. Our goal is to understand the effects of diversity, interaction strenghts and ecological network structure on the volume of parameter space leading to feasible equilibria, i.e., ones in which all populations have positive abundances. We develop a geometrical framework to study the range of conditions necessary for feasible coexistence in both mutualistic and consumer-resource systems. Using analytical and numerical methods, we show that feasibility is determined by just a handful of quantities describing the interactions, yielding a nontrivial complexity-feasibility relationship. Analyzing more than 100 empirical networks, we show that the range of coexistence conditions in mutualistic systems can be analytically predicted by means of a null model of random interactions, whereas food webs are characterized by smaller coexistence domains than those expected by chance. Finally, we characterize the geometric shape of the feasibility domain, thereby identifying the direction of perturbations that are more likely to cause extinctions. Interestingly, the structure of mutualistic interactions leads to very heterogeneous responses to perturbations, making those systems more fragile than expected by chance.

q-bio.PE↗

The influence of dispersal on a predator-prey system with two habitats

Dispersal between different habitats influences the dynamics and stability of populations considerably. Furthermore, these effects depend on the local interactions of a population with other species. Here, we perform a general and comprehensive study of the simplest possible system that includes dispersal and local interactions, namely a 2-patch 2-species system. We evaluate the impact of dispersal on stability and on the occurrence of bifurcations, including pattern forming bifurcations that lead to spatial heterogeneity, in 19 different classes of models with the help of the generalized modelling approach. We find that dispersal often destabilizes equilibria, but it can stabilize them if it increases population losses. If dispersal is nonrandom, i.e. if emigration or immigration rates depend on population densities, the correlation of stability with migration rates is positive in part of the models. We also find that many systems show all four types of bifurcations and that antisynchronous oscillations occur mostly with nonrandom dispersal.

physics.bio-ph↗

Information transfer through a signaling module with feedback: a perturbative approach

Signal transduction in biological cells is effected by signaling pathways that typically include multiple feedback loops. Here we analyze information transfer through a prototypical signaling module with biochemical feedback. The module switches stochastically between an inactive and active state; the input to the module governs the activation rate while the output (i.e., the product concentration) perturbs the inactivation rate. Using a novel perturbative approach, we compute the rate with which information about the input is gained from observation of the output. We obtain an explicit analytical result valid to first order in feedback strength and to second order in the strength of input. The total information gained during an extended time interval is found to depend on the feedback strength only through the total number of activation/inactivation events.

physics.bio-ph↗

Biomechanical conditions of walking

The development of rehabilitation training program for lower limb injury does not usually include gait pattern design. This paper introduced a gait pattern design by using equations (conditions of walking). Following the requirements of reducing force to the injured side to avoid further injury, we developed a lower limb gait pattern to shorten the stride length so as to reduce walking speed, to delay the stance phase of the uninjured side and to reduce step length of the uninjured side. This gait pattern was then verified by the practice of a rehabilitation training of an Achilles tendon rupture patient, whose two-year rehabilitation training (with 24 tests) has proven that this pattern worked as intended. This indicates that rehabilitation training program for lower limb injury can rest on biomechanical conditions of walking based on experimental evidence.

physics.med-ph↗

Hydrodynamic oscillations and variable swimming speed in squirmers close to repulsive walls

We present a lattice Boltzmann study of the hydrodynamics of a fully resolved squirmer, radius R, confined in a slab of fluid between two no-slip walls. We show that the coupling between hydrodynamics and short-range repulsive interactions between the swimmer and the surface can lead to hydrodynamic trapping of both pushers and pullers at the wall, and to hydrodynamic oscillations in the case of a pusher. We further show that a pusher moves significantly faster when close to a surface than in the bulk, whereas a puller undergoes a transition between fast motion and a dynamical standstill according to the range of the repulsive interaction. Our results critically require near-field hydrodynamics; they further suggest that it should be possible to control density and speed of squirmers at a surface by tuning the range of steric and electrostatic swimmer-wall interactions.

cond-mat.soft↗

Differential stability of DNA based on salt concentration

Intracellular positive ions neutralise negative charges on the phosphates of a DNA strand conferring greater strength on the hydrogen bonds that connect complementary strands into a double helix and so confer enhanced stability. Beyond a certain value of salt concentration, the DNA molecule displays a unstable nature {\it in vivo} as well as {\it in vitro}. We consider a wide range of salt concentrations and study the stability of the DNA double helix using a statistical model. Through numerical calculations we attempt to explain the different behaviour exhibited by DNA molecules in this range. We compare our results with experimental data and find a close agreement.

cond-mat.soft↗

Quantum Cognition: The possibility of processing with nuclear spins in the brain

The possibility that quantum processing with nuclear spins might be operative in the brain is proposed and then explored. Phosphorus is identified as the unique biological element with a nuclear spin that can serve as a qubit for such putative quantum processing - a neural qubit - while the phosphate ion is the only possible qubit-transporter. We identify the "Posner molecule", $\text{Ca}_9 (\text{PO}_4)_6$, as the unique molecule that can protect the neural qubits on very long times and thereby serve as a (working) quantum-memory. A central requirement for quantum-processing is quantum entanglement. It is argued that the enzyme catalyzed chemical reaction which breaks a pyrophosphate ion into two phosphate ions can quantum entangle pairs of qubits. Posner molecules, formed by binding such phosphate pairs with extracellular calcium ions, will inherit the nuclear spin entanglement. A mechanism for transporting Posner molecules into presynaptic neurons during a "kiss and run" exocytosis, which releases neurotransmitters into the synaptic cleft, is proposed. Quantum measurements can occur when a pair of Posner molecules chemically bind and subsequently melt, releasing a shower of intra-cellular calcium ions that can trigger further neurotransmitter release and enhance the probability of post-synaptic neuron firing. Multiple entangled Posner molecules, triggering non-local quantum correlations of neuron firing rates, would provide the key mechanism for neural quantum processing. Implications, both in vitro and in vivo, are briefly mentioned.

q-bio.NC↗

Automated Analysis of Behavioural Variability and Filial Imprinting of Chicks (G. gallus), using Autonomous Robots

Inter-individual variability has various impacts in animal social behaviour. This implies that not only collective behaviours have to be studied but also the behavioural variability of each member composing the groups. To understand those effects on group behaviour, we develop a quantitative methodology based on automated ethograms and autonomous robots to study the inter-individual variability among social animals. We choose chicks of \textit{Gallus gallus domesticus} as a classic social animal model system for their suitability in laboratory and controlled experimentation. Moreover, even domesticated chicken present social structures implying forms or leadership and filial imprinting. We develop an imprinting methodology on autonomous robots to study individual and social behaviour of free moving animals. This allows to quantify the behaviours of large number of animals. We develop an automated experimental methodology that allows to make relatively fast controlled experiments and efficient data analysis. Our analysis are based on high-throughput data allowing a fine quantification of individual behavioural traits. We quantify the efficiency of various state-of-the-art algorithms to automate data analysis and produce automated ethograms. We show that the use of robots allows to provide controlled and quantified stimuli to the animals in absence of human intervention. We quantify the individual behaviour of 205 chicks obtained from hatching after synchronized fecundation. Our results show a high variability of individual behaviours and of imprinting quality and success. Three classes of chicks are observed with various level of imprinting. Our study shows that the concomitant use of autonomous robots and automated ethograms allows detailed and quantitative analysis of behavioural patterns of animals in controlled laboratory experiments.

q-bio.QM↗

Second Quantization Approach to Stochastic Epidemic Models

We show how the standard field theoretical language based on creation and annihilation operators may be used for a straightforward derivation of closed master equations describing the population dynamics of multivariate stochastic epidemic models. In order to do that, we introduce an SIR-inspired stochastic model for hepatitis C virus epidemic, from which we obtain the time evolution of the mean number of susceptible, infected, recovered and chronically infected individuals in a population whose total size is allowed to change.

physics.bio-ph↗