Heptatic liquid quasi-crystals by colloidal lithographic pre-assembly.

HYPOTHESIS: We hypothesize that pre-assembled lithographic Brownian seven-fold quasi-crystals (QCs) of colloidal tiles at high densities can exhibit a heptatic liquid quasi-crystal (LQC) phase upon release; such heptatic LQCs can undergo heterogeneous dynamics at different length scales, reflecting the underlying symmetry, corrugation, and hierarchy of local sets of tiles. EXPERIMENTS: We design, fabricate, and release a seven-fold QC composed of three differently shaped rhombic tiles using the method of lithographically pre-assembled monolayers (litho-PAMs). High resolution optical microscopy enables spatio-temporal particle tracking of Brownian fluctuations of many tiles in a large area over a long time. We develop an edge-proximity tessellation method for analyzing nearest neighboring particles that can be applied to assemblies and dense systems of complex shapes. FINDINGS: A fluctuating heptatic LQC phase is identified at high tile area fractions. Heterogenous dynamics and order at different length scales indicate diverse, hierarchical motif structures. We show that certain motifs can collectively rotate without any cage breaking, leading to alterations of the local tile-structure reminiscent of phason-flips in atomic QCs; this rotation causes a slow decline in the system's spatial order. We anticipate that edge-proximity tessellation will help elucidate phase transitions of other systems made of diverse building blocks having significant geometrical complexity at multiple length scales.

Comorbidity clusters in patients with rheumatoid arthritis identify a patient phenotype with a favourable prognosis.

OBJECTIVES: We aimed to cluster patients with rheumatoid arthritis (RA) based on comorbidities and then examine the association between these clusters and RA disease activity and mortality. METHODS: In this population-based study, residents of an eight-county region with prevalent RA on 1 January 2015 were identified. Patients were followed for vital status until death, last contact or 31 December 2021. Diagnostic codes for 5 years before the prevalence date were used to define 55 comorbidities. Latent class analysis was used to cluster patients based on comorbidity patterns. Standardised mortality ratios were used to assess mortality. RESULTS: A total of 1643 patients with prevalent RA (72% female; 94% white; median age 64 years, median RA duration 7 years) were studied. Four clusters were identified. Cluster 1 (n=686) included patients with few comorbidities, and cluster 4 (n=134) included older patients with 10 or more comorbidities. Cluster 2 (n=200) included patients with five or more comorbidities and high prevalences of depression and obesity, while cluster 3 (n=623) included the remainder. RA disease activity and survival differed across the clusters, with cluster 1 demonstrating more remission and mortality comparable to the general population. CONCLUSIONS: More than 40% of patients with prevalent RA did not experience worse mortality than their peers without RA. The cluster with the worst prognosis (<10% of patients with prevalent RA) was older, had more comorbidities and had less disease-modifying antirheumatic drug and biological use compared with the other clusters. Comorbidity patterns may hold the key to moving beyond a one-size-fits-all perspective of RA prognosis.

Engineering multicomponent tissue by spontaneous adhesion of myogenic and adipogenic microtissues cultured with customized scaffolds.

The integration of intramuscular fat-or marbling-into cultured meat will be critical for meat texture, mouthfeel, flavor, and thus consumer appeal. However, culturing muscle tissue with marbling is challenging since myocytes and adipocytes have different media and scaffold requirements for optimal growth and differentiation. Here, we present an approach to engineer multicomponent tissue using myogenic and adipogenic microtissues. The key innovation in our approach is the engineering of myogenic and adipogenic microtissues using scaffolds with customized physical properties; we use these microtissues as building blocks that spontaneously adhere to produce multicomponent tissue, or marbled cultured meat. Myocytes are grown and differentiated on gelatin nanofiber scaffolds with aligned topology that mimic the aligned structure of skeletal muscle and promotes the formation of myotubes in both primary rabbit skeletal muscle and murine C2C12 cells. Pre-adipocytes are cultured and differentiated on edible gelatin microbead scaffolds, which are customized to have a physiologically-relevant stiffness, and promote lipid accumulation in both primary rabbit and murine 3T3-L1 pre-adipocytes. After harvesting and stacking the individual myogenic and adipogenic microtissues, we find that the resultant multicomponent tissues adhere into intact structures within 6-12 h in culture. The resultant multicomponent 3D tissue constructs show behavior of a solid material with a Young's modulus of âˆ¼ 2 ± 0.4 kPa and an ultimate tensile strength of âˆ¼ 23 ± 7 kPa without the use of additional crosslinkers. Using this approach, we generate marbled cultured meat with âˆ¼ mm to âˆ¼ cm thickness, which has a protein content of âˆ¼ 4 ± 2 g/100 g that is comparable to a conventionally produced Wagyu steak with a protein content of âˆ¼ 9 ± 4 g/100 g. We show the translatability of this layer-by-layer assembly approach for microtissues across primary rabbit cells, murine cell lines, as well as for gelatin and plant-based scaffolds, which demonstrates a strategy to generate edible marbled meats derived from different species and scaffold materials.

Jamming and depletion in extremely bidisperse mixtures of microscale emulsions and nanoemulsions.

While much attention has been given to jamming of granular and colloidal particles having monomodal size distributions, jamming of systems having more complex size distributions remains an interesting direction. We create concentrated, disordered binary mixtures of size-fractionated nanoscale and microscale oil-in-water emulsions, which are stabilized by the same common ionic surfactant, and measure the optical transport properties, microscale droplet dynamics, and mechanical shear rheological properties of these mixtures over a wide range of relative and total droplet volume fractions. Simple effective medium theories do not explain all of our observations. Instead, we show that our measurements are consistent with more complex collective behavior in extremely bidisperse systems, involving an effective continuous phase that governs nanodroplet jamming, as well as depletion attractions between microscale droplets induced by nanoscale droplets.

Patients with ACPA-positive and ACPA-negative rheumatoid arthritis show different serological autoantibody repertoires and autoantibody associations with disease activity.

Patients with rheumatoid arthritis (RA) can test either positive or negative for circulating anti-citrullinated protein antibodies (ACPA) and are thereby categorized as ACPA-positive (ACPA+) or ACPA-negative (ACPA-), respectively. In this study, we aimed to elucidate a broader range of serological autoantibodies that could further explain immunological differences between patients with ACPA+ RA and ACPA- RA. On serum collected from adult patients with ACPA+ RA (n = 32), ACPA- RA (n = 30), and matched healthy controls (n = 30), we used a highly multiplex autoantibody profiling assay to screen for over 1600 IgG autoantibodies that target full-length, correctly folded, native human proteins. We identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA- RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies with significantly higher abundances in ACPA+ RA patients and ACPA- RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons; this provides further evidence of immunological differences between these two RA subgroups despite sharing similar symptoms. On the other hand, we identified 30 and 25 autoantibodies with lower abundances in ACPA+ RA and ACPA- RA, respectively, of which 8 autoantibodies were common in both comparisons; we report for the first time that the depletion of certain autoantibodies may be linked to this autoimmune disease. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with Clinical Disease Activity Index, but associate differently depending on patients' ACPA status. In all, we present candidate autoantibody biomarker signatures associated with ACPA status and disease activity in RA, providing a promising avenue for patient stratification and diagnostics.

Signatures of nanoemulsion jamming and unjamming in stimulated-echo NMR.

The unjamming of elastic concentrated nanoemulsions into viscous dilute nanoemulsions, through dilution with the continuous phase, offers interesting opportunities for a pulsed-field gradient (PFG) NMR, particularly if the nanoemulsion is designed to take advantage of the nuclear specificity offered by NMR. Here, we make and study size-fractionated oil-in-water nanoemulsions using a perfluorinated copolymer silicone oil that is highly insoluble in the aqueous continuous phase. By studying these nanoemulsions using ^{19}F stimulated-echo PFG-NMR, we avoid any contribution from the aqueous continuous phase, which contains a nonfluorinated ionic surfactant. We find a dramatic change in the ^{19}F PFG-NMR decays at high field-gradient strengths as the droplet volume fraction, ϕ, is lowered through dilution. At high ϕ, observed decays as a function of field-gradient strength exhibit decay-to-plateau behavior indicating the jamming of nanodroplets, which contain ^{19}F probe molecules, in an elastic material reminiscent of a nanoporous solid. In contrast, at lower ϕ, only a simple decay is observed, indicating that the nanodroplets have unjammed and can diffuse over much larger distances. Through a comparison with bulk mechanical rheometry, we show that this dramatic change coincides with the loss of low-frequency shear elasticity of the nanoemulsion.

Microflow of nanoemulsion threads in surfactant solutions.

We experimentally investigate the microfluidic flow of oil-in-water nanoemulsions in aqueous sodium dodecyl sulfate (SDS) solutions having different concentrations and injection flow rates. A coaxial microfluidic device is employed to explore the behavior of nanoemulsion threads in these sheathing SDS solutions. Using two high-speed cameras, which simultaneously capture both top and side views, we reveal a variety of flow phenomena, ranging from simple core-annular flow to complex flows, such as gravitational, inertial, and buckling thread flows. By analyzing these complex flows, we develop a methodology that elucidates the relationship of core-annular and gravitational flows at low flow rates. Further, we examine the off-axis displacements and bending of core threads at large flow rates, and we study the buckling dynamics of nanoemulsion threads subjected to osmotic stresses caused by large SDS concentrations in the sheathing fluid.

Structural elucidation of polydopamine facilitated by ionic liquid solvation.

Minimal understanding of the formation mechanism and structure of polydopamine (pDA) and its natural analogue, eumelanin, impedes the practical application of these versatile polymers and limits our knowledge of the origin of melanoma. The lack of conclusive structural evidence stems from the insolubility of these materials, which has spawned significantly diverse suggestions of pDA's structure in the literature. We discovered that pDA is soluble in certain ionic liquids. Using these ionic liquids (ILs) as solvents, we present an experimental methodology to solvate pDA, enabling us to identify pDA's chemical structure. The resolved pDA structure consists of self-assembled supramolecular aggregates that contribute to the increasing complexity of the polymer. The underlying molecular energetics of pDA solvation and a macroscopic picture of the disruption of the aggregates using IL solvents have been investigated, along with studies of the aggregation mechanism in water.

Complex optical transport, dynamics, and rheology of intermediately attractive emulsions.

Introducing short-range attractions in Brownian systems of monodisperse colloidal spheres can substantially impact their structures and consequently their optical transport and rheological properties. Here, for size-fractionated colloidal emulsions, we show that imposing an intermediate strength of attraction, well above but not much larger than thermal energy ([Formula: see text] [Formula: see text], through micellar depletion leads to a striking notch in the measured inverse mean free path of optical transport, [Formula: see text], as a function of droplet volume fraction, [Formula: see text]. This notch, which appears between the hard-sphere glass transition, [Formula: see text], and maximal random jamming, [Formula: see text], implies the existence of a greater population of compact dense clusters of droplets, as compared to tenuous networks of droplets in strongly attractive emulsion gels. We extend a prior decorated core-shell network model for strongly attractive colloidal systems to include dense non-percolating clusters that do not contribute to shear rigidity. By constraining this extended model using the measured [Formula: see text], we improve and expand the microrheological interpretation of diffusing wave spectroscopy (DWS) experiments made on attractive colloidal systems. Our measurements and modeling demonstrate richness and complexity in optical transport and shear rheological properties of dense, disordered colloidal systems having short-range intermediate attractions between moderately attractive glasses and strongly attractive gels.

Curvature-assisted self-assembly of Brownian squares on cylindrical surfaces.

HYPOTHESIS: We hypothesize that curved surfaces, including cylindrical surfaces, which go beyond prior experiments using flat surfaces, can significantly influence and alter the phase behavior and self-assembly of dense two-dimensional systems of Brownian colloids. EXPERIMENTS: Here, we report a first experimental study regarding the self-assembly of Brownian square platelets with an edge length L = 2.3 µm on cylindrical surfaces having different curvatures; these platelets are subjected to a depletion attraction in order to form a monolayer above the cylindrical surface, yet have nearly hard interactions within the monolayer. Simulations are also performed to confirm and explain the experimental observations. FINDINGS: Phase diagrams as a function of curvature are determined experimentally. Interestingly, hexagonal rotator crystal structures are observed for tubes having radii > 10.9L, but a tetratic phase is seen instead for the 10.9L tube at the corresponding platelet area fractions. We show that this transition is caused by the curvature-induced orientation-dependence of the depletion attraction between the squares and the underlying cylindrical surface. Brownian dynamics simulation results confirm the experimental observations and also illustrate helical structures formed by squares packing on cylinders. Our results demonstrate a way towards control over the self-assembly of anisotropic particles through curvature and depletion-attraction-induced orientational confinement.

Depletion torques between anisotropic colloidal particles.

We explore how the entropic notion of depletion forces between spheres, introduced by Asakura and Oosawa, can be extended to depletion torques that affect the orientations of colloidal particles having complex shapes. In prior experimental work, systems of microscale plate-like particles in the presence of a nanoscale depletion agent have been shown to form polymer-like columnar chains; restoring depletion torques act to align lithographically-structured platelets within a chain orientationally about the chain's axis. We consider depletion torques corresponding to parallel, face-to-face, near-contact pair interactions for complex-shaped, plate-like, prismatic lithographic particles in colloidal dispersions containing a spherical nanoscale depletion agent. We calculate depletion torques for a wide variety of such particles, including rotationally symmetric, asymmetric, achiral, chiral, and elongated particles. Moreover, we determine depletion torques between two non-parallel proximate square platelets connected by a lossless hinge along a common edge. Our investigations show that depletion torques can be tailored through lithographic or synthetic design of specific geometrical features in the shapes of particles.

Brownian lithographic polymers of steric lock-and-key colloidal linkages.

We design and lithographically fabricate two-dimensional preassembled colloidal linkages of custom-shaped, discrete, mobile microscale tiles that are sterically coupled together by lock-and-key sub-tile features, yielding hinge-like bonds between separate tiles. These mobile colloidal linkages, which we call polylithomers, provide top-down, preconfigured, morphologically controllable analogs of fluctuating molecular polymers. We illustrate the versatility of this approach by fabricating and studying curvilinear, branched, bridged-spiral, dendritic, and mesh-like polylithomers having controllable preassembled dimensions, topologies, configurations, intrinsic local curvatures, persistence lengths, and bond extensibilities. By advancing anisotropic particle tracking routines to handle lock-and-key tiles, we measure the dynamic conformational changes of polylithomers caused by Brownian excitations to the monomer scale, revealing markedly large bond extensibilities. Beyond modeling fluctuating semiflexible molecular polymers, polylithomers provide access to unusual polymer morphologies and bonding potentials that have not yet been synthesized through other kinds of assembly methods using either molecular or colloidal monomers.

Self-motion and heterogeneous droplet dynamics in moderately attractive dense emulsions.

We show that diffusing wave spectroscopy (DWS) is sensitive to the presence of a moderate short-range attraction between droplets in uniform fractionated colloidal emulsions near and below the jamming point associated with monodisperse hard spheres. This moderate interdroplet attraction, induced by micellar depletion, has an energy of about ∼2.4kBT, only somewhat larger than thermal energy. Although changes in the mean free path of optical transport caused by this moderate depletion attraction are small, DWS clearly reveals an additional secondary decay-to-plateau in the intensity autocorrelation function at long times that is not present when droplet interactions are nearly hard. We hypothesize that this secondary decay-to-plateau does not reflect the average self-motion of individual droplets experiencing Brownian excitations, but instead results from heterogeneous dynamics involving a sub-population of droplets that still experience bound motion yet with significantly larger displacements than the average. By effectively removing the contribution of this secondary decay-to-plateau, which is linked to greater local heterogeneity in droplet structure caused by the moderate attraction, we obtain self-motion mean square displacements (MSDs) of droplets that reflect only the initial primary decay-to-plateau. Moreover, we show that droplet self-motion primary plateau MSDs can be interpreted using the generalized Stokes-Einstein relation of passive microrheology, yielding quantitative agreement with plateau elastic shear moduli measured mechanically.

Prediction of lattice energy of benzene crystals: A robust theoretical approach.

We present an inexpensive and robust theoretical approach based on the fragment molecular orbital methodology and the spin-ratio scaled second-order Møller-Plesset perturbation theory to predict the lattice energy of benzene crystals within 2 kJ⋅mol-1 . Inspired by the Harrison method to estimate the Madelung constant, the proposed approach calculates the lattice energy as a sum of two- and three-body interaction energies between a reference molecule and the surrounding molecules arranged in a sphere. The lattice energy converges rapidly at a radius of 13 Å. Adding the corrections to account for a higher correlated level of theory and basis set superposition for the Hartree Fock (HF) level produced a lattice energy of -57.5 kJ⋅mol-1 for the benzene crystal structure at 138 K. This estimate is within 1.6 kJ⋅mol-1 off the best theoretical prediction of -55.9 kJ⋅mol-1 . We applied this approach to calculate lattice energies of the crystal structures of phase I and phase II-polymorphs of benzene-observed at a higher temperature of 295 K. The stability of these polymorphs was correctly predicted, with phase II being energetically preferred by 3.7 kJ⋅mol-1 over phase I. The proposed approach gives a tremendous potential to predict stability of other molecular crystal polymorphs.

Predicting Entropic Effects of Water Mixing with Ionic Liquids Containing Anions of Strong Hydrogen Bonding Ability: Role of the Cation.

Ionic liquids (ILs) such as choline dihydrogen phosphate exhibit an extraordinary solubilizing ability for proteins such as cytochrome C when mixed with 20 wt % water. Most widely used imidazolium-based ionic liquids coupled with dihydrogen phosphate do not exhibit the same solubilizing properties, suggesting that a multifunctional cation such as choline might play a key role in enhancing these properties of ionic liquid mixtures with water. In this theoretical work, we compare intermolecular interactions between the water molecule and ionic liquid ions in two ion-paired clusters of choline- and 1-butyl-3-methyl-imidazolium-based ionic liquids coupled with acetate, dihydrogen phosphate, and mesylate. Gibbs free energy (GFE) of solvation of water in these ionic liquids was calculated. Incorporation of a water molecule into ionic liquid clusters was accompanied by negative GFEs of solvation in both types of cations. These results were in good agreement with previously reported experimental GFEs of solvation of water in ILs. Compared to imidazolium-based clusters, strong interionic interactions of choline ionic liquids resulted in more negative GFEs due to their smaller deformation upon the addition of a water molecule, with dihydrogen phosphate and mesylate predicting the lowest GFEs of -30.1 and -43.5 kJ/mol-1, respectively. Lower GFEs of solvation of water in choline-based clusters were also accompanied with smaller entropic penalties, suggesting that water easily incorporates itself into the existing ionic network. Analysis of the intramolecular bonds within the water molecule showed that the choline hydroxyl group donates electron density to the neighboring water molecule, leading to additional polarization. The predicted infrared spectra of clusters of ionic liquids with water showed a pronounced red shift due to strongly polarized O-H bonds, in excellent agreement with the experimentally measured infrared spectra of ionic liquid mixtures with water. Increased polarization of water in choline-based ionic liquids undoubtedly creates more effective solvents for stabilizing biological molecules such as proteins.

Emergent tetratic order in crowded systems of rotationally asymmetric hard kite particles.

Considering multi-body systems of monodisperse hard Brownian particles, it remains challenging to predict the forms of order that can emerge in their dense assembled structures. Surprisingly, here, using Monte Carlo simulations, we show that tetratic-ordered phases emerge in a dense two-dimensional system of hard kites that are rotationally asymmetric and have opposite 72° and α ≈ 90° internal angles. We observe a new tetragonal rectangular crystal (TRX) phase possessing (quasi-)long-range fourfold molecular-orientational order. We propose a method based on local polymorphic configurations of neighboring particle pairs (LPC-NPPs) to understand this emergent tetratic order and show that LPC-NPPs can be useful for predicting orientational order in such systems. To examine the dependence of the tetratic order on α, we apply LPC-NPP analysis to other hard kites for 54° ≤ α ≤ 144°. Our work provides insight into the creation of novel ordered materials by rationally designing particle shape based on anticipated LPC-NPPs.

Diffusing wave microrheology of strongly attractive dense emulsions.

We advance the microrheological interpretation of optical diffusing wave spectroscopy (DWS) measurements of strongly attractive emulsions at dense droplet volume fractions, ϕ. Beyond accounting for collective scattering, we show that measuring the mean free path of optical transport over a wide range of ϕ is necessary to quantify the effective size of the DWS probes, which we infer to be local dense clusters of droplets through a decorated core-shell network model. This approach yields microrheological elastic shear moduli that are in quantitative agreement with mechanical rheometry.

Longitudinal Occurrence and Predictors of Patient-Provider Discordance Between Global Assessments of Disease Activity in Rheumatoid Arthritis: A Case-Control Study.

OBJECTIVE: To identify longitudinal predictors of discordance between patients with rheumatoid arthritis (RA) and their health care providers, where patient global assessment of disease activity is substantially higher than provider global assessment. METHODS: This retrospective case-control study included 102 cases with positive discordance (i.e., ≥25 mm between patient and provider global assessments) and 102 controls without discordance who were matched for age, sex, RA duration, and Clinical Disease Activity Index (CDAI) score. Data were collected at the baseline visit (date of diagnosis or earliest available visit), the index visit (participation in a previous cross-sectional study), and at up to 11 additional visits before the index visit. Data included patient characteristics, disease activity measures, Disease Activity Score in 28 joints (3-variable) using the C-reactive protein level (DAS28-CRP), and medications. Data were analyzed by using linear and logistic regression models with smoothing splines for nonlinear trends. RESULTS: Overall, the mean age was 63 years, 75% of patients were female, and the mean RA duration was 10 years. Compared with controls, cases had higher rates of discordant visits during the 4 years before the index visit, and they had a higher CDAI score and DAS28-CRP earlier in the disease course. Cases more frequently had antinuclear antibodies, nonerosive disease, prior depression, or prior use of antidepressants or fibromyalgia medications. Disease-modifying medication use was not different between cases and controls. CONCLUSION: The findings inform new hypotheses about the relationships of disease activity and antinuclear antibodies to the later occurrence of positive discordance among patients with RA.

Long-wavelength fluctuations and anomalous dynamics in 2-dimensional liquids.

In 2-dimensional systems at finite temperature, long-wavelength Mermin-Wagner fluctuations prevent the existence of translational long-range order. Their dynamical signature, which is the divergence of the vibrational amplitude with the system size, also affects disordered solids, and it washes out the transient solid-like response generally exhibited by liquids cooled below their melting temperatures. Through a combined numerical and experimental investigation, here we show that long-wavelength fluctuations are also relevant at high temperature, where the liquid dynamics do not reveal a transient solid-like response. In this regime, these fluctuations induce an unusual but ubiquitous decoupling between long-time diffusion coefficient D and structural relaxation time τ, where [Formula: see text], with [Formula: see text] Long-wavelength fluctuations have a negligible influence on the relaxation dynamics only at extremely high temperatures in molecular liquids or at extremely low densities in colloidal systems.

Band-collision gel electrophoresis.

Electrophoretic mobility shift assays are widely used in gel electrophoresis to study binding interactions between different molecular species loaded into the same well. However, shift assays can access only a subset of reaction possibilities that could be otherwise seen if separate bands of reagent species might instead be collisionally reacted. Here, we adapt gel electrophoresis by fabricating two or more wells in the same lane, loading these wells with different reagent species, and applying an electric field, thereby producing collisional reactions between propagating pulse-like bands of these species, which we image optically. For certain pairs of anionic and cationic dyes, propagating bands pass through each other unperturbed; yet, for other pairs, we observe complexing and precipitation reactions, indicating strong attractive interactions. We generalize this band-collision gel electrophoresis (BCGE) approach to other reaction types, including acid-base, ligand exchange, and redox, as well as to colloidal species in passivated large-pore gels.