Experimental observations of fractal landscape dynamics in a dense emulsion.

Many soft and biological materials display so-called 'soft glassy' dynamics; their constituents undergo anomalous random motions and complex cooperative rearrangements. A recent simulation model of one soft glassy material, a coarsening foam, suggested that the random motions of its bubbles are due to the system configuration moving over a fractal energy landscape in high-dimensional space. Here we show that the salient geometrical features of such high-dimensional fractal landscapes can be explored and reliably quantified, using empirical trajectory data from many degrees of freedom, in a model-free manner. For a mayonnaise-like dense emulsion, analysis of the observed trajectories of oil droplets quantitatively reproduces the high-dimensional fractal geometry of the configuration path and its associated local energy minima generated using a computational model. That geometry in turn drives the droplets' complex random motion observed in real space. Our results indicate that experimental studies can elucidate whether the similar dynamics in different soft and biological materials may also be due to fractal landscape dynamics.

Exploring canyons in glassy energy landscapes using metadynamics.

The complex physics of glass-forming systems is controlled by the structure of the low-energy portions of their potential energy landscapes. Here we report that a modified metadynamics algorithm efficiently explores and samples low-energy regions of such high-dimensional landscapes. In the energy landscape for a model foam, our algorithm finds and descends meandering canyons in the landscape, which contain dense clusters of energy minima along their floors. Similar canyon structures in the energy landscapes of two model glass formers-hard sphere fluids and the Kob-Andersen glass-allow us to reach high densities and low energies, respectively. In the hard sphere system, fluid configurations are found to form continuous regions that cover the canyon floors up to densities well above the jamming transition. For the Kob-Andersen glass former, our technique samples low-energy states with modest computational effort, with the lowest energies found approaching the predicted Kauzmann limit.

Advancing Mental Health Screening in Schools: Innovative, Field-Tested Practices and Observed Trends During a 15-Month Learning Collaborative.

Schools are well positioned to facilitate early identification and intervention for youth with emerging mental health needs through universal mental health screening. Early identification of mental health concerns via screening can improve long-term student development and success, but schools face logistical challenges and lack of pragmatic guidance to develop local screening policies and practices. This study summarizes mental health screening practices tested by six school districts participating in a 15-month learning collaborative. Qualitative analysis of 42 Plan-Do-Study-Act cycles revealed that districts tested quality improvement changes across seven screening practice areas, with all teams conducting at least one test to: 1) build a foundation; and 2) identify resources, logistics and administration processes. Quantitative data indicated that the average percentage of total students screened increased from 0% to 22% (range = 270 - 4,850 students screened at follow-up). Together, these results demonstrate how school districts not currently engaged in mental health screening can apply small, specific tests of change to develop a locally-tailored, practical and scalable process to screen for student mental health concerns. Lessons learned are provided to inform future directions for school-based teams.

Measuring Cytoskeletal Mechanical Fluctuations and Rheology with Active Micropost Arrays.

The dynamics of the cellular actomyosin cytoskeleton are crucial to many aspects of cellular function. Here, we describe techniques that employ active micropost array detectors (AMPADs) to measure cytoskeletal rheology and mechanical force fluctuations. The AMPADS are arrays of flexible poly(dimethylsiloxane) (PDMS) microposts with magnetic nanowires embedded in a subset of microposts to enable actuation of those posts via an externally applied magnetic field. Techniques are described to track the magnetic microposts' motion with nanometer precision at up to 100 video frames per second to measure the local cellular rheology at well-defined positions. Application of these high-precision tracking techniques to the full array of microposts in contact with a cell also enables mapping of the cytoskeletal mechanical fluctuation dynamics with high spatial and temporal resolution. This article describes (1) the fabrication of magnetic micropost arrays, (2) measurement protocols for both local rheology and cytoskeletal force fluctuation mapping, and (3) special-purpose software routines to reduce and analyze these data. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Fabrication of magnetic micropost arrays Basic Protocol 2: Data acquisition for cellular force fluctuations on non-magnetic micropost arrays Basic Protocol 3: Data acquisition for local cellular rheology measurements with magnetic microposts Basic Protocol 4: Data reduction: determining microposts' motion Basic Protocol 5: Data analysis: determining local rheology from magnetic microposts Basic Protocol 6: Data analysis for force fluctuation measurements Support Protocol 1: Fabrication of magnetic Ni nanowires by electrodeposition Support Protocol 2: Configuring Streampix for magnetic rheology measurements.

Probing lipid membrane bending mechanics using gold nanorod tracking.

Lipid bilayer membranes undergo rapid bending undulations with wavelengths from tens of nanometers to tens of microns due to thermal fluctuations. Here, we probe such undulations and the membranes' mechanics by measuring the time-varying orientation of single gold nanorods (GNRs) adhered to the membrane, using high-speed dark field microscopy. In a lipid vesicle, such measurements allow the determination of the membrane's viscosity, bending rigidity, and tension as well as the friction coefficient for sliding of the monolayers over one another. The in-plane rotation of the GNR is hindered by undulations in a tension dependent manner, consistent with simulations. The motion of single GNRs adhered to the plasma membrane of living cultured cells similarly reveals the membrane's complex physics and coupling to the cell's actomyosin cortex.

Pervasive cytoquakes in the actomyosin cortex across cell types and substrate stiffness.

The actomyosin cytoskeleton enables cells to resist deformation, crawl, change their shape and sense their surroundings. Despite decades of study, how its molecular constituents can assemble together to form a network with the observed mechanics of cells remains poorly understood. Recently, it has been shown that the actomyosin cortex of quiescent cells can undergo frequent, abrupt reconfigurations and displacements, called cytoquakes. Notably, such fluctuations are not predicted by current physical models of actomyosin networks, and their prevalence across cell types and mechanical environments has not previously been studied. Using micropost array detectors, we have performed high-resolution measurements of the dynamic mechanical fluctuations of cells' actomyosin cortex and stress fiber networks. This reveals cortical dynamics dominated by cytoquakes-intermittent events with a fat-tailed distribution of displacements, sometimes spanning microposts separated by 4 µm, in all cell types studied. These included 3T3 fibroblasts, where cytoquakes persisted over substrate stiffnesses spanning the tissue-relevant range of 4.3 kPa-17 kPa, and primary neonatal rat cardiac fibroblasts and myofibroblasts, human embryonic kidney cells and human bone osteosarcoma epithelial (U2OS) cells, where cytoquakes were observed on substrates in the same stiffness range. Overall, these findings suggest that the cortex self-organizes into a marginally stable mechanical state whose physics may contribute to cell mechanical properties, active behavior and mechanosensing.

Interfacial Flow around Brownian Colloids.

Understanding the flow created by particle motion at interfaces is a critical step toward understanding hydrodynamic interactions and colloidal self organization. We have developed correlated displacement velocimetry to measure flow fields around interfacially trapped Brownian particles. These flow fields can be decomposed into interfacial hydrodynamic multipoles, including force monopole and dipole flows. These structures provide key insights essential to understanding the interface's mechanical response. Importantly, the flow structure shows that the interface is incompressible for scant surfactant near the ideal gaseous state and contains information about interfacial properties and hydrodynamic coupling with the bulk fluid. The same dataset can be used to predict the response of the interface to applied, complex forces, enabling virtual experiments that produce higher order interfacial multipoles.

Shear-driven rolling of DNA-adhesive microspheres.

Many biologically important cell binding processes, such as the rolling of leukocytes in the vasculature, are multivalent, being mediated by large numbers of weak binding ligands. Quantitative agreement between experiments and models of rolling has been elusive and often limited by the poor understanding of the binding and unbinding kinetics of the ligands involved. Here, we present a cell-free experimental model for such rolling, consisting of polymer microspheres whose adhesion to a glass surface is mediated by ligands with well-understood force-dependent binding free energy-short complementary DNA strands. We observe robust rolling activity for certain values of the shear rate and the grafted DNA strands' binding free energy and force sensitivity. The simulation framework developed to model leukocyte rolling, adhesive dynamics, quantitatively captures the mean rolling velocity and lateral diffusivity of the experimental particles using known values of the experimental parameters. Moreover, our model captures the velocity variations seen within the trajectories of single particles. Particle-to-particle variations can be attributed to small, plausible differences in particle characteristics. Overall, our findings confirm that state-of-the-art adhesive dynamics simulations are able to capture the complex physics of particle rolling, boding well for their extension to modeling more complex systems of rolling cells.

Hydrodynamic and frictional modulation of deformations in switchable colloidal crystallites.

Displacive transformations in colloidal crystals may offer a pathway for increasing the diversity of accessible configurations without the need to engineer particle shape or interaction complexity. To date, binary crystals composed of spherically symmetric particles at specific size ratios have been formed that exhibit floppiness and facile routes for transformation into more rigid structures that are otherwise not accessible by direct nucleation and growth. There is evidence that such transformations, at least at the micrometer scale, are kinetically influenced by concomitant solvent motion that effectively induces hydrodynamic correlations between particles. Here, we study quantitatively the impact of such interactions on the transformation of binary bcc-CsCl analog crystals into close-packed configurations. We first employ principal-component analysis to stratify the explorations of a bcc-CsCl crystallite into orthogonal directions according to displacement. We then compute diffusion coefficients along the different directions using several dynamical models and find that hydrodynamic correlations, depending on their range, can either enhance or dampen collective particle motions. These two distinct effects work synergistically to bias crystallite deformations toward a subset of the available outcomes.

Interfacial microrheology and tensiometry in a miniature, 3-d printed Langmuir trough.

We introduce a new approach for manipulating and studying complex fluid interfacial systems, that enables simultaneous tensiometry to measure surface pressure and high-performance interfacial shear microrheology. In contrast to existing techniques, we use a miniature Langmuir trough produced by 3-d printing methods, which fits on the stage of a conventional inverted microscope and which allows compression and stretching of the fluid-fluid interfaces at a constant bulk fluid volume. The tensiometry measurement relies on the quantitative imaging of a curved meniscus separate from the flat interface being imaged under the microscope. We first demonstrate that this approach can measure the interfacial tension of simple fluid-fluid and polymer-laden interfaces with an accuracy comparable to the pendant drop apparatus and Wilhelmy plates. We then study the mechanics of an adsorbed protein layer formed at an air-water (a-w) interface by simultaneously measuring its surface pressure and its interfacial viscosity. To perform two-point interfacial microrheology, micrometer-sized probes spread on the interface are tracked to 5 nm precision with very low drift, yielding measurements of interfacial viscosity having a wide dynamic range and high sensitivity (10-9-10-1Nsm-1).

How do women and health care professionals view hormonal long-acting reversible contraception? Results from an international survey.

Purpose: Evidence from real-world settings is important to provide an accurate picture of health care delivery. We investigated use of long-acting reversible contraception (LARC) in women aged 15-49 years.Materials and methods: Two surveys, one of women and one of health care professionals (HCPs), were conducted in parallel across seven countries. Participating women completed an online survey to assess contraceptive awareness, current method of contraception, age, and experience with current contraceptive method. HCPs participated in an online survey to provide practice-level information and three anonymous charts of hormonal LARC users.Results: Of 6903 women who completed the survey, 3225 provided information about their current primary contraception method. Overall, 16% used LARC methods, while 52% used oral contraceptives (OCs). Of hormonal intrauterine system users, 72% described their experience as 'very favourable', compared with only 53% of women using OCs. Anonymous patient records (n = 1605) were provided by 550 HCPs who completed the online survey. Most women (64%) had used short-acting reversible contraception before switching to LARC. Physicians perceived 56-84% of LARC users to be highly satisfied with their current form of contraception.Conclusions: Although usage of LARC was low, most women using LARC were highly satisfied with their method of contraception.

Dissecting fat-tailed fluctuations in the cytoskeleton with active micropost arrays.

The ability of animal cells to crawl, change their shape, and respond to applied force is due to their cytoskeleton: A dynamic, cross-linked network of actin protein filaments and myosin motors. How these building blocks assemble to give rise to cells' mechanics and behavior remains poorly understood. Using active micropost array detectors containing magnetic actuators, we have characterized the mechanics and fluctuations of cells' actomyosin cortex and stress fiber network in detail. Here, we find that both structures display remarkably consistent power law viscoelastic behavior along with highly intermittent fluctuations with fat-tailed distributions of amplitudes. Notably, this motion in the cortex is dominated by occasional large, step-like displacement events, with a spatial extent of several micrometers. Overall, our findings for the cortex appear contrary to the predictions of a recent active gel model, while suggesting that different actomyosin contractile units act in a highly collective and cooperative manner. We hypothesize that cells' actomyosin components robustly self-organize into marginally stable, plastic networks that give cells' their unique biomechanical properties.

Deposition of sticky spheres in channel flow: Modeling of surface coverage evolution requires accurate sphere-sphere collision hydrodynamics.

We analyzed the role of hydrodynamic interactions in a microfluidic channel flow containing a dilute suspension of micron-scale colloidal spheres (0.03%, 0.1%, 0.3% volume fraction) engineered to adhere onto a collector patch on the channel wall at wall shear rates of 9.3-930 s-1. Particle-wall adhesion was mediated by single-stranded DNA oligomers grafted onto the spheres and the glass channel wall, producing well-defined interactions via DNA strand base pairing. Particle positions in the flow were evolved using Brownian dynamics simulations in which hydrodynamic interactions between moving particles and the channel walls and/or adhered particles were computed off-line using a series of local simulations that explicitly resolve the fluid flow at the particle scale. By systematically varying the nature of hydrodynamic interactions captured in the Brownian dynamics simulations, we find that the interactions between moving and adhered particles represents the single most important physical element in such models. Once captured sufficiently accurately, the resulting models are able to predict coarse variables such as the overall particle coverage evolution, as well as more subtle characteristics, such as the microstructural distribution of the adhered particles.

Nanoscale Rheology and Anisotropic Diffusion Using Single Gold Nanorod Probes.

The complex rotational and translational Brownian motion of anisotropic particles depends on their shape and the viscoelasticity of their surroundings. Because of their strong optical scattering and chemical versatility, gold nanorods would seem to provide the ultimate probes of rheology at the nanoscale, but the suitably accurate orientational tracking required to compute rheology has not been demonstrated. Here we image single gold nanorods with a laser-illuminated dark-field microscope and use optical polarization to determine their three-dimensional orientation to better than one degree. We convert the rotational diffusion of single nanorods in viscoelastic polyethylene glycol solutions to rheology and obtain excellent agreement with bulk measurements. Extensions of earlier models of anisotropic translational diffusion to three dimensions and viscoelastic fluids give excellent agreement with the observed motion of single nanorods. We find that nanorod tracking provides a uniquely capable approach to microrheology and provides a powerful tool for probing nanoscale dynamics and structure in a range of soft materials.

Interaction Heterogeneity can Favorably Impact Colloidal Crystal Nucleation.

Colloidal particles with short-ranged attractions, e.g., micron-scale spheres functionalized with single-stranded DNA oligomers, are susceptible to becoming trapped in disordered configurations even when a crystalline arrangement is the ground state. Moreover, for reasons that are not well understood, seemingly minor variations in the particle formulation can lead to dramatic changes in the crystallization outcome. We demonstrate, using a combination of equilibrium and nonequilibrium computer simulations, that interaction heterogeneity-variations in the energetic interactions among different particle pairs in the population-may favorably impact crystal nucleation. Specifically, interaction heterogeneity is found to lower the free energy barrier to nucleation via the formation of clusters comprised preferentially of strong-binding particle pairs. Moreover, gelation is inhibited by "spreading out over time" the nucleation process, resulting in a reduced density of stable nuclei, allowing each to grow unhindered and larger. Our results suggest a simple and robust approach for enhancing colloidal crystallization near the "sticky sphere" limit, and support the notion that differing extents of interaction heterogeneity arising from various particle functionalization protocols may contribute to the otherwise unexplained variations in crystallization outcomes reported in the literature.

Self-assembly with colloidal clusters: facile crystal design using connectivity landscape analysis.

Recent experimental and theoretical studies demonstrate that prefabricated micron-scale colloidal clusters functionalized with DNA oligomers offer a practical way for introducing anisotropic interactions, significantly extending the scope of DNA-mediated colloidal assembly, and enabling the formation of interesting crystalline superstructures that are otherwise inaccessible with short-ranged, spherically symmetric interactions. However, it is apparent that the high-dimensional parameter space that defines the geometric and interaction properties of such systems poses an obstacle to assembly design and optimization. Here, we present a geometrical analysis that generates connectivity landscapes for target superstructures, greatly reducing the space over which subsequent experimental trials must search. We focus on several superstructures that are assembled from binary systems comprised of 'merged' or 'sintered' tetrahedral clusters and single spheres. We also validate and extend the analytical constraint approach with direct MD simulations of superstructure nucleation and growth.

Dimpled Polyhedral Colloids Formed by Colloidal Crystal Templating.

Many approaches to the self-assembly of interesting microstructures rely on particles with engineered shapes. We create dimpled solid particles by molding oil droplets in the interstices of a close-packed colloidal crystal and polymerizing them in situ, resulting in particles containing multiple spherical dimples arranged with various polyhedral symmetries. Monodisperse micrometer-sized droplets of 3-methacryloxypropyltrimethoxysilane (TPM) are mixed with an excess of polystyrene (PS) microspheres (2.58 µm) and allowed to sediment, forming colloidal crystals with TPM droplets inside their interstitial sites. When these crystals are compressed by partial drying, the trapped droplets wet the multiple microspheres surrounding them, forming a three-dimensional capillary bridge with the symmetry of the interstitial spaces, and then mild heating triggers polymerization in situ. Depending on the initial particle volume fraction and extent of drying, a high yield of dimpled particles having different symmetries including tetrahedra and cubes is obtained. The fractional yield of different shapes varies with the size ratio of the TPM droplets and the PS microspheres forming the template lattice. Sedimentation velocity fractionation methods are effective for enrichment of specific symmetries but not complete purification. Our approach for forming polyhedral particles should be readily scalable to larger samples and smaller sized particles if desired.

Colloidal crystals with diamond symmetry at optical lengthscales.

Future optical materials promise to do for photonics what semiconductors did for electronics, but the challenge has long been in creating the structure they require-a regular, three-dimensional array of transparent microspheres arranged like the atoms in a diamond crystal. Here we demonstrate a simple approach for spontaneously growing double-diamond (or B32) crystals that contain a suitable diamond structure, using DNA to direct the self-assembly process. While diamond symmetry crystals have been grown from much smaller nanoparticles, none of those previous methods suffice for the larger particles needed for photonic applications, whose size must be comparable to the wavelength of visible light. Intriguingly, the crystals we observe do not readily form in previously validated simulations; nor have they been predicted theoretically. This finding suggests that other unexpected microstructures may be accessible using this approach and bodes well for future efforts to inexpensively mass-produce metamaterials for an array of photonic applications.

Building Strong Partnerships: Education and Mental Health Systems Working Together to Advance Behavioral Health Screening in Schools.

In this article, we have introduced a key challenge confronting the fields of education and mental health: the need for early detection of EBDs among students and a framework for early response to their needs. Next, we offered a potential solution: prioritizing strong, integrated partnerships between education and mental health systems. Following this discussion, we provided two illustrations (1) teacher-completed behavior screening within a Ci3T model of prevention in an elementary school setting and (2) student self-reported mental health screening in the high school setting. The differences in the screening measures used in the two illustrations are important. The first illustrates universal behavior screening conducted as part of regular school practices to inform instruction. Teacher-completed screeners are based on observed student behaviors, with screening as a way to measure and monitor teachers' observations. The second illustrates the use of mental health screening (student self-report). Additional protections for self-report measures must be afforded, such as parent/guardian permission and opt-out options as discussed in the high school illustration. Finally, we have offered a call to action, posing considerations for next steps for researchers, practitioners, and policymakers. We hope this concluding article in the four-issue 2017 volume of the Report on Emotional & Behavioral Disorders in Youth will help to propel improvements in research, practice, and policy of the foundational issue of early identification of students in need of successful school behavioral health programs.