Automated Tomographic Assessment of Structural Defects of Freeze-Dried Pharmaceuticals.

The topology and surface characteristics of lyophilisates significantly impact the stability and reconstitutability of freeze-dried pharmaceuticals. Consequently, visual quality control of the product is imperative. However, this procedure is not only time-consuming and labor-intensive but also expensive and prone to errors. In this paper, we present an approach for fully automated, non-destructive inspection of freeze-dried pharmaceuticals, leveraging robotics, computed tomography, and machine learning.

TSS-ConvNet for electrical impedance tomography image reconstruction.

Objective.The objective of this study was to propose a novel data-driven method for solving ill-posed inverse problems, particularly in certain conditions such as time-difference electrical impedance tomography for detecting the location and size of bubbles inside a pipe.Approach.We introduced a new layer architecture composed of three paths: spatial, spectral, and truncated spectral paths. The spatial path processes information locally, whereas the spectral and truncated spectral paths provide the network with a global receptive field. This unique architecture helps eliminate the ill-posedness and nonlinearity inherent in the inverse problem. The three paths were designed to be interconnected, allowing for an exchange of information on different receptive fields with varied learning abilities. Our network has a bottleneck architecture that enables it to recover signal information from noisy redundant measurements. We named our proposed model truncated spatial-spectral convolutional neural network (TSS-ConvNet).Main results.Our model demonstrated superior accuracy with relatively high resolution on both simulation and experimental data. This indicates that our approach offers significant potential for addressing ill-posed inverse problems in complex conditions effectively and accurately.Significance.The TSS-ConvNet overcomes the receptive field limitation found in most existing models that only utilize local information in Euclidean space. We trained the network on a large dataset covering various configurations with random parameters to ensure generalization over the training samples.

Shear zones in granular mixtures of hard and soft particles with high and low friction.

Granular materials show inhomogeneous flows characterized by strain localization. When strain is localized in a sheared granular material, rigid regions of a nearly undeformed state are separated by shear bands, where the material yields and flows. The characteristics of the shear bands are determined by the geometry of the system, the micromechanical material properties, and the kinematics at the particle level. For a split-bottom shear cell, recent experimental work has shown that mixtures of hard, frictional and soft, nearly frictionless particles exhibit wider shear zones than samples with only one of the two components. To explain this finding, we investigate the shear zone properties and the stress response of granular mixtures using discrete element simulations. We show that both interparticle friction and elastic modulus determine the shear-band properties and packing density of granular mixtures of various mixing ratios, but their stress response depends strongly on the interparticle friction. Our study provides a fundamental understanding of the micromechanics of shear band formation in granular mixtures.

Influence of silicon nanocone on cell membrane self-sealing capabilities for targeted drug delivery-Computer simulation study.

Efficient and non-invasive techniques of cargo delivery to biological cells are the focus of biomedical research because of their great potential importance for targeted drug therapy. Therefore, much effort is being made to study the characteristics of using nano-based biocompatible materials as systems that can facilitate this task while ensuring appropriate self-sealing of the cell membrane. Here, we study the effects of indentation and withdrawal of nanocone on phospholipid membrane by applying steered molecular dynamics (SMD) technique. Our results show that the withdrawal process directly depends on the initial position of the nanocone. The average force and work are considerably more significant in case of the withdrawal starting from a larger depth. This result is attributed to stronger hydrophobic interactions between the nanocone and lipid tails of the membrane molecules. Furthermore, when the indenter was started from the lower initial depth, the number of lipids removed from the membrane was several times smaller than the deeper indentation. The choice of the least invasive method for nanostructure-assisted drug delivery is crucial for possible applications in medicine. Therefore, the results presented in this work might be helpful in efficient and safe drug delivery with nanomaterials.

A device for studying fluid-induced cracks under mixed-mode loading conditions using x-ray tomography.

We introduce an innovative instrument designed to investigate fluid-induced fractures under mixed loading conditions, including uniaxial tension and shear stress, in gels and similar soft materials. Equipped with sensors for measuring force, torque, and fluid pressure, the device is tailored for compatibility with x-ray tomography scanners, enabling non-invasive 3D analysis of crack geometries. To showcase its capabilities, we conducted a study examining crack-front segmentation in a hydrogel subjected to air pressure and a combination of tension and shear stress.

Macroscopic analogue to entangled polymers.

The entangled structure of polymeric materials is often described as resembling a bowl of spaghetti, swarms of earthworms, or snakes. These analogies not only illustrate the concept, but form the foundation of polymer physics. However, the similarity between these macroscopic, athermal systems and polymers in terms of topology remains uncertain. To better understand this relationship, we conducted an experiment using X-ray tomography to study the structure of arrays of linear rubber bands. We found that, similar to linear polymers, the average number of entanglements increases linearly with the length of the ribbons. Additionally, we observed that entanglements are less frequent near the surface of the container, where there are also more ends, similar to what has been seen in trapped polymers. These findings provide the first experimental evidence supporting the visualization of polymer structures using macroscopic, athermal analogues, confirming the initial intuitive insights of the pioneers of polymer physics.

Collective motion of granular matter subjected to swirling excitation.

A two-dimensional granular packing under horizontally circular shaking exhibits various collective motion modes where nonuniform density distribution and correlated dynamics are present. For intermediate packing density and oscillation amplitude, a condensed phase travels around the container's side wall in the clockwise direction, while the oscillation itself is set anticlockwise. Further increasing the packing density towards that of hexagonal packing, the whole packing rotates collectively in the clockwise direction. The core of the packing rotates as a solid and is separated from the boundary by a fluid-like layer. Both motion modes are associated with the asymmetric motion of particles close to the side wall in one oscillation cycle, where the dependence of particle velocity on the local density plays a key role.

Fingerprints of viscoelastic subdiffusion in random environments: Revisiting some experimental data and their interpretations.

Many experimental studies revealed subdiffusion of various nanoparticles in diverse polymer and colloidal solutions, cytosol and plasma membrane of biological cells, which are viscoelastic and, at the same time, highly inhomogeneous randomly fluctuating environments. The observed subdiffusion often combines features of ergodic fractional Brownian motion (reflecting viscoelasticity) and nonergodic jumplike non-Markovian diffusional processes (reflecting disorder). Accordingly, several theories were proposed to explain puzzling experimental findings. Below we show that some of the significant and profound published experimental results are better rationalized within the viscoelastic subdiffusion approach in random environments, which is based on generalized Langevin dynamics in random potentials, than some earlier proposed theories.

Nonequilibrium Phase Transition to Anomalous Diffusion and Transport in a Basic Model of Nonlinear Brownian Motion.

We investigate a basic model of nonlinear Brownian motion in a thermal environment, where nonlinear friction interpolates between viscous Stokes and dry Coulomb friction. We show that superdiffusion and supertransport emerge as a nonequilibrium critical phenomenon when such a Brownian motion is driven out of thermal equilibrium by a constant force. Precisely at the edge of a phase transition, velocity fluctuations diverge asymptotically and diffusion becomes superballistic. The autocorrelation function of velocity fluctuations in this nonergodic regime exhibits a striking aging behavior.

Surfactants and rotelles in active chiral fluids.

Surfactant molecules migrate to interfaces, reduce interfacial tension, and form micelles. All of these behaviors occur at or near equilibrium. Here, we describe active analogs of surfactants that operate far from equilibrium in active chiral fluids. Unlike molecular surfactants, the amphiphilic character of surfactants in active chiral fluids is a consequence of their activity. Our fluid of choice is a mixture of spinners that demixes into left-handed and right-handed chiral fluid domains. We realize spinners in experiment with three-dimensionally printed vibrots. Vibrot surfactants are chains of vibrots containing both types of handedness. Experiments demonstrate the affinity of double-stranded chains to interfaces, where they glide along and act as mixing agents. Simulations access larger systems in which single-stranded chains form spinning vesicles, termed rotelles. Rotelles are the chiral analogs of micelles. Rotelle formation is a ratchet mechanism catalyzed by the vorticity of the chiral fluid and only exist far from equilibrium.

Growing Old Too Early: Skeletal Muscle Single Fiber Biomechanics in Ageing R349P Desmin Knock-in Mice Using the MyoRobot Technology.

Muscle biomechanics relies on active motor protein assembly and passive strain transmission through cytoskeletal structures. The desmin filament network aligns myofibrils at the z-discs, provides nuclear-sarcolemmal anchorage and may also serve as memory for muscle repositioning following large strains. Our previous analyses of R349P desmin knock-in mice, an animal model for the human R350P desminopathy, already depicted pre-clinical changes in myofibrillar arrangement and increased fiber bundle stiffness. As the effect of R349P desmin on axial biomechanics in fully differentiated single muscle fibers is unknown, we used our MyoRobot to compare passive visco-elasticity and active contractile biomechanics in single fibers from fast- and slow-twitch muscles from adult to senile mice, hetero- or homozygous for the R349P desmin mutation with wild type littermates. We demonstrate that R349P desmin presence predominantly increased axial stiffness in both muscle types with a pre-aged phenotype over wild type fibers. Axial viscosity and Ca2+-mediated force were largely unaffected. Mutant single fibers showed tendencies towards faster unloaded shortening over wild type fibers. Effects of aging seen in the wild type appeared earlier in the mutant desmin fibers. Our single-fiber experiments, free of extracellular matrix, suggest that compromised muscle biomechanics is not exclusively attributed to fibrosis but also originates from an impaired intermediate filament network.

Migrating Shear Bands in Shaken Granular Matter.

When dense granular matter is sheared, the strain is often localized in shear bands. After some initial transient these shear bands become stationary. Here, we introduce a setup that periodically creates horizontally aligned shear bands which then migrate upward through the sample. Using x-ray radiography we demonstrate that this effect is caused by dilatancy, the reduction in volume fraction occurring in sheared dense granular media. Further on, we argue that these migrating shear bands are responsible for the previously reported periodic inflating and collapsing of the material.

Hydrodynamic memory can boost enormously driven nonlinear diffusion and transport.

Hydrodynamic memory force or Basset force has been known since the 19th century. Its influence on Brownian motion remains, however, mostly unexplored. Here we investigate its role in nonlinear transport and diffusion within a paradigmatic model of tilted washboard potential. In this model, a giant enhancement of driven diffusion over its potential-free limit [Phys. Rev. Lett. 87, 010602 (2001)PRLTAO0031-900710.1103/PhysRevLett.87.010602] presents a well-established paradoxical phenomenon. In the overdamped limit, it occurs at a critical tilt of vanishing potential barriers. However, for weak damping, it takes place surprisingly at another critical tilt, where the potential barriers are clearly expressed. Recently we showed [Phys. Rev. Lett. 123, 180603 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.180603] that Basset force could make such a diffusion enhancement enormously large. In this paper, we discover that even for moderately strong damping, where the overdamped theory works very well when the memory effects are negligible, substantial hydrodynamic memory unexpectedly makes a strong impact. First, the diffusion boost occurs at nonvanishing potential barriers and can be orders of magnitude larger. Second, transient anomalous diffusion regimes emerge over many time decades and potential periods. Third, particles' mobility can also be dramatically enhanced, and a long transient supertransport regime emerges.

Packing structure of semiflexible rings.

Unraveling the packing structure of dense assemblies of semiflexible rings is not only fundamental for the dynamical description of polymer rings, but also key to understand biopackaging, such as observed in circular DNA of viruses or genome folding. Here we use X-ray tomography to study the geometrical and topological features of disordered packings of rubber bands in a cylindrical container. Assemblies of short bands assume a liquid-like disordered structure, with short-range orientational order, and reveal only minor influence of the container. In the case of longer bands, the confinement causes folded configurations and the bands interpenetrate and entangle. Most of the systems are found to display a threading network which percolates the system. Surprisingly, for long bands whose diameter is more than twice the diameter of the container, we found that all bands interpenetrate each other, in a complex fully entangled structure.

Interactions of a short hyaluronan chain with a phospholipid membrane.

Hyaluronic acid and phospholipids are two components that are present in the synovial fluid, and both are implicated as important facilitators of joint lubrication. In this work we aim to clarify how hyaluronic acid interacts with a phospholipid bilayer through their molecular interactions at the bilayer surface. To this end we performed molecular dynamics simulations of one hyaluronic acid molecule at a phospholipid bilayer in aqueous solution. The simulations were carried out for two aqueous solutions of equal concentrations, containing either NaCl or CaCl2. We analyzed hydrogen bonds, hydrophobic contacts and cation mediated bridges to clarify how hyaluoronic acid binds to a phospholipid bilayer. The analysis shows that calcium ions promote longer lasting bonds between the species as they create calcium ion bridges between the carboxylate group of hyaluronic acid and the phosphate group of the phospholipid. This type of additional bonding does not significantly influence the total number of contact created, but rather stabilizes the contact. The presented results can facilitate understanding of the role of hyaluronic acid and phospholipid interactions in terms of lubrication of articular cartilage.

The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice.

Mutations in the Des gene coding for the muscle-specific intermediate filament protein desmin lead to myopathies and cardiomyopathies. We previously generated a R349P desmin knock-in mouse strain as a patient-mimicking model for the corresponding most frequent human desmin mutation R350P. Since nothing is known about the age-dependent changes in the biomechanics of affected muscles, we investigated the passive and active biomechanics of small fiber bundles from young (17-23 wks), adult (25-45 wks) and aged (>60 wks) heterozygous and homozygous R349P desmin knock-in mice in comparison to wild-type littermates. We used a novel automated biomechatronics platform, the MyoRobot, to perform coherent quantitative recordings of passive (resting length-tension curves, visco-elasticity) and active (caffeine-induced force transients, pCa-force, 'slack-tests') parameters to determine age-dependent effects of the R349P desmin mutation in slow-twitch soleus and fast-twitch extensor digitorum longus small fiber bundles. We demonstrate that active force properties are not affected by this mutation while passive steady-state elasticity is vastly altered in R349P desmin fiber bundles compatible with a pre-aged phenotype exhibiting stiffer muscle preparations. Visco-elasticity on the other hand, was not altered. Our study represents the first systematic age-related characterization of small muscle fiber bundle preparation biomechanics in conjunction with inherited desminopathy.

Correction of beam hardening in X-ray radiograms.

The intensity of a monochromatic X-ray beam decreases exponentially with the distance it has traveled inside a material; this behavior is commonly referred to as Beer-Lambert's law. Knowledge of the material-specific attenuation coefficient µ allows us to determine the thickness of a sample from the intensity decrease the beam has experienced. However, classical X-ray tubes emit a polychromatic bremsstrahlung-spectrum. And the attenuation coefficients of all materials depend on the photon energy: photons with high energy are attenuated less than photons with low energy. In consequence, the X-ray spectrum changes while traveling through the medium; due to the relative increase in high energy photons, this effect is called beam hardening. For this varying spectrum, the Beer-Lambert law only remains valid if µ is replaced by an effective attenuation coefficient µeff which depends not only on the material but also on its thickness x and the details of the X-ray setup used. We present here a way to deduce µeff(x) from a small number of auxiliary measurements using a phenomenological model. This model can then be used to determine an unknown material thickness or in the case of a granular media its volume fraction.

Orientation-dependent properties of nanoparticle impact.

The mechanical properties of nanoparticles cannot be reliably described by bulk material characteristics due to their atomic structure, leading to pronounced anisotropic behavior. By means of molecular dynamics simulations, we study the impact of 5-nm Ag particles on an adhesive rigid wall. We show that the main characteristics of the impact such as the coefficient of normal restitution, the sticking probability, the maximal contact force, and the degree of plastic deformation of the particle depend sensitively on the angular orientation of the nanoparticle prior to the impact. We introduce the scalar parameter Ω describing the orientation and show that the impact characteristics can be described as functions of Ω.

Systematic Onset of Periodic Patterns in Random Disk Packings.

We report evidence of a surprising systematic onset of periodic patterns in very tall piles of disks deposited randomly between rigid walls. Independently of the pile width, periodic structures are always observed in monodisperse deposits containing up to 10^{7} disks. The probability density function of the lengths of disordered transient phases that precede the onset of periodicity displays an approximately exponential tail. These disordered transients may become very large when the channel width grows without bound. For narrow channels, the probability density of finding periodic patterns of a given period displays a series of discrete peaks, which, however, are washed out completely when the channel width grows.