Mechanical theory of nonequilibrium coexistence and motility-induced phase separation.

Nonequilibrium phase transitions are routinely observed in both natural and synthetic systems. The ubiquity of these transitions highlights the conspicuous absence of a general theory of phase coexistence that is broadly applicable to both nonequilibrium and equilibrium systems. Here, we present a general mechanical theory for phase separation rooted in ideas explored nearly a half-century ago in the study of inhomogeneous fluids. The core idea is that the mechanical forces within the interface separating two coexisting phases uniquely determine coexistence criteria, regardless of whether a system is in equilibrium or not. We demonstrate the power and utility of this theory by applying it to active Brownian particles, predicting a quantitative phase diagram for motility-induced phase separation in both two and three dimensions. This formulation additionally allows for the prediction of novel interfacial phenomena, such as an increasing interface width while moving deeper into the two-phase region, a uniquely nonequilibrium effect confirmed by computer simulations. The self-consistent determination of bulk phase behavior and interfacial phenomena offered by this mechanical perspective provide a concrete path forward toward a general theory for nonequilibrium phase transitions.

Rapid Quantification of Ammonium Nitrate and Urea Nitrate Using Liquid Chromatography-High-Resolution Orbitrap Mass Spectrometry.

Resolution and sensitivity improvements in mass spectrometry technology have enabled renewed attempts at solving challenging analytical issues. One such issue involves the analysis of energetic ionic species. Energetic ionic species make up an important class of chemical materials, and a more robust and versatile analytical platform would provide tremendous value to the analytical community. Initial attempts at quantification of energetic ionic species employed high-resolution time-of-flight measurements with crown ether (CE) complexation and flow injection analysis (FIA). In this investigation, ammonium nitrate (AN) and urea nitrate (UN) in the presence of a crown ether complexation agent were explored by using high-resolution orbitrap mass spectrometry. Product ion scans of these signature complexes reveal positive identification of these energetic ionic species. Finally, quantification was demonstrated for both flow injection and liquid chromatography-mass spectrometry (LC-MS) analysis, suggesting the capability for routine and rapid analysis of these energetic ionic materials.

Interpersonal and Community-Level Influences Across the PrEP Cascade Among Young Adult Latinx Men who Have Sex with Men Living in a US-Mexico Border Region: A Qualitative Study.

Latinx men who have sex with men (MSM) are an at-risk population for new HIV diagnoses. Pre-exposure prophylaxis (PrEP) is a suite of biomedical approaches to prevent HIV infection. Latinx MSM are less likely to take PrEP compared to non-Latinx White MSM. This qualitative study identified interpersonal- and community-level barriers and facilitators of PrEP among young adult Latinx MSM. Using stratified purposeful sampling, 27 Latinx men, ages 19-29 years and living in a US-Mexico border region, completed self-report demographic surveys and participated in semi-structured in-depth interviews assessing barriers and facilitators to PrEP. Directed content analysis was used to identify both a priori and emerging themes. Most participants reported that other people, including peers, friends, partners, and health care providers were both supportive and discouraging of PrEP use. Participants' intersectional identities as members of both Latinx and LGBTQ+ (Lesbian, Gay, Bisexual, Transgender, Queer) communities both hindered and facilitated PrEP use.

Confined active matter in external fields.

We analyze a dilute suspension of active particles confined between walls and subjected to fields that can modulate particle speed as well as orientation. Generally, the particle distribution is different in the bulk compared to near the walls. In the bulk, particles tend to accumulate in the regions of low speed, but in the presence of an orienting field normal to the walls, particles rotate to align with the field and accumulate in the field direction. At the walls, particles tend to accumulate pointing into the walls and thereby exert pressure on walls. But the presence of strong orienting fields can cause the particles to reorient away from the walls, and hence shows a possible mechanism for preventing contamination of surfaces. The pressure at the walls depends on the wall separation and the field strengths. This work demonstrates how multiple fields with different functionalities can be used to control active matter under confinement.

Tuning nonequilibrium phase transitions with inertia.

In striking contrast to equilibrium systems, inertia can profoundly alter the structure of active systems. Here, we demonstrate that driven systems can exhibit effective equilibrium-like states with increasing particle inertia, despite rigorously violating the fluctuation-dissipation theorem. Increasing inertia progressively eliminates motility-induced phase separation and restores equilibrium crystallization for active Brownian spheres. This effect appears to be general for a wide class of active systems, including those driven by deterministic time-dependent external fields, whose nonequilibrium patterns ultimately disappear with increasing inertia. The path to this effective equilibrium limit can be complex, with finite inertia sometimes acting to accentuate nonequilibrium transitions. The restoration of near equilibrium statistics can be understood through the conversion of active momentum sources to passive-like stresses. Unlike truly equilibrium systems, the effective temperature is now density dependent, the only remnant of the nonequilibrium dynamics. This density-dependent temperature can in principle introduce departures from equilibrium expectations, particularly in response to strong gradients. Our results provide additional insight into the effective temperature ansatz while revealing a mechanism to tune nonequilibrium phase transitions.

Partitioning of active particles into porous media.

Passive Brownian particles partition homogeneously between a porous medium and an adjacent fluid reservoir. In contrast, active particles accumulate near boundaries and can therefore preferentially partition into the porous medium. Understanding how active particles interact with and partition into such an environment is important for optimizing particle transport. In this work, both the initial transient and steady behavior as active swimmers partition into a porous medium from a bulk fluid reservoir are investigated. At short times, the particle number density in the porous medium exhibits an oscillatory behavior due to the particles' ballistic motion when time t < τR, where τR is the reorientation time of the active particles. At longer times, t > L2/Dswim, the particles diffuse from the reservoir into the porous medium, leading to a steady state concentration partitioning. Here, L is the characteristic length scale of the porous medium and Dswim = U0/d(d - 1), where U0 is the intrinsic swim speed of the particles,  = U0τR is the particles' run, or persistence, length, and d is the dimension of the reorientation process. An analytical prediction is developed for this partitioning for spherical obstacles connected to a fluid reservoir in both two and three dimensions based on the Smoluchowski equation and a macroscopic mechanical momentum balance. The analytical prediction agrees well with Brownian dynamics simulations.

Gay Community Involvement and Condomless Anal Sex Among Sexual Minority Men in the USA.

Sexual minority men (SMM) remain disproportionately burdened by sexually transmitted infections. Although gay community involvement has been theorized to be protective against many negative health outcomes, research examining the association between community involvement and condomless anal sex (CAS) has yielded conflicting results. The current study, conducted between 2018-2020, examined whether the importance one places on various aspects of community involvement was associated with CAS among a sample of young adult SMM aged 18-34 years with body image concerns (N = 180). Gay community involvement was measured using the Importance of Gay Community Scale, and the results of an exploratory factor analysis indicated the presence of two factors: "social activism" and "going out/nightlife." A zero-inflated Poisson regression was conducted to examine the association between gay "social activism," "going out/nightlife," and their interaction with the number of CAS partners. Upon examining a significant interaction, "social activism" had a protective effect against CAS at low levels of "going out/nightlife," but this effect was non-significant at higher levels. These results suggest that encouraging gay community involvement through activism could be effective at reducing CAS and addressing the health disparity that exists within this population.

Trapped-particle microrheology of active suspensions.

In microrheology, the local rheological properties, such as the viscoelasticity of a complex fluid, are inferred from the free or forced motion of embedded colloidal probe particles. Theoretical machinery developed for forced-probe microrheology of colloidal suspensions focused on either constant-force (CF) or constant-velocity (CV) probes, while in experiments, neither the force nor the kinematics of the probe is fixed. More importantly, the constraint of CF or CV introduces a difficulty in the meaningful quantification of the fluctuations of the probe due to a thermodynamic uncertainty relation. It is known that, for a Brownian particle trapped in a harmonic potential well, the product of the standard deviations of the trap force and the particle position is dkBT in d dimensions, with kBT being the thermal energy. As a result, if the force (position) is not allowed to fluctuate, the position (force) fluctuation becomes infinite. To allow the measurement of fluctuations in theoretical studies, in this work, we consider a microrheology model in which the embedded probe is dragged along by a moving harmonic potential so that both its position and the trap force are allowed to fluctuate. Starting from the full Smoluchowski equation governing the dynamics of N hard active Brownian particles, we derive a pair Smoluchowski equation describing the dynamics of the probe as it interacts with one bath particle by neglecting hydrodynamic interactions among particles in the dilute limit. From this, we determine the mean and the variance (i.e., fluctuation) of the probe position in terms of the pair probability distribution. We then characterize the behavior of the system in the limits of both weak and strong trap. By taking appropriate limits, we show that our generalized model can be reduced to the well-studied CF or CV microrheology models.

Machine learning for phase behavior in active matter systems.

We demonstrate that deep learning techniques can be used to predict motility-induced phase separation (MIPS) in suspensions of active Brownian particles (ABPs) by creating a notion of phase at the particle level. Using a fully connected network in conjunction with a graph neural network we use individual particle features to predict to which phase a particle belongs. From this, we are able to compute the fraction of dilute particles to determine if the system is in the homogeneous dilute, dense, or coexistence region. Our predictions are compared against the MIPS binodal computed from simulation. The strong agreement between the two suggests that machine learning provides an effective way to determine the phase behavior of ABPs and could prove useful for determining more complex phase diagrams.

Theory for the Casimir effect and the partitioning of active matter.

Active Brownian particles (ABPs) distribute non-homogeneously near surfaces, and understanding how this depends on system properties-size, shape, activity level, etc.-is essential for predicting and exploiting the behavior of active matter systems. Active particles accumulate at no-flux surfaces owing to their persistent swimming, which depends on their intrinsic swim speed and reorientation time, and are subject to confinement effects when their run or persistence length is comparable to the characteristic size of the confining geometry. It has been observed in simulations that two parallel plates experience a "Casimir effect" and attract each other when placed in a dilute bath of ABPs. In this work, we provide a theoretical model based on the Smoluchowski equation and a macroscopic mechanical momentum balance to analytically predict this attractive force. We extend this method to describe the concentration partitioning of active particles between a confining channel and a reservoir, showing that the ratio of the concentration in the channel to that in the bulk increases as either run length increases or channel height decreases. The theoretical results agree well with Brownian dynamics simulations and finite element calculations.

Core-shell droplets and microcapsules formed through liquid-liquid phase separation of a colloid-polymer mixture.

Microcapsules allow for the controlled containment, transport, and release of cargoes ranging from pharmaceuticals to fragrances. Given the interest from a variety of industries in microcapsules and other core-shell structures, a multitude of fabrication strategies exist. Here, we report on a method relying on a mixture of temperature-responsive microgel particles, poly(N-isopropylacrylamide) (pNIPAM), and a polymer which undergo fluid-fluid phase separation. At room temperature this mixture separates into colloid-rich (liquid) and colloid-poor (gas) fluids. By heating the sample above a critical temperature where the microgel particles shrink dramatically and develop a more deeply attractive interparticle potential, the droplets of the colloid-rich phase become gel-like. As the temperature is lowered back to room temperature, these droplets of gelled colloidal particles reliquefy and phase separation within the droplet occurs. This phase separation leads to colloid-poor droplets within the colloid-rich droplets surrounded by a continuous colloid-poor phase. The gas/liquid/gas all-aqueous double emulsion lasts only a few minutes before a majority of the inner droplets escape. However, the colloid-rich shell of the core-shell droplets can solidify with the addition of salt. That this method creates core-shell structures with a shell composed of stimuli-sensitive microgel colloidal particles using only aqueous components makes it attractive for encapsulating biological materials and making capsules that respond to changes in, for example, temperature, salt concentration, or pH.

The "isothermal" compressibility of active matter.

We demonstrate that the mechanically defined "isothermal" compressibility behaves as a thermodynamic-like response function for suspensions of active Brownian particles. The compressibility computed from the active pressure-a combination of the collision and unique swim pressures-is capable of predicting the critical point for motility induced phase separation, as expected from the mechanical stability criterion. We relate this mechanical definition to the static structure factor via an active form of the thermodynamic compressibility equation and find the two to be equivalent, as would be the case for equilibrium systems. This equivalence indicates that compressibility behaves like a thermodynamic response function, even when activity is large. Finally, we discuss the importance of the phase interface when defining an active chemical potential. Previous definitions of the active chemical potential are shown to be accurate above the critical point but breakdown in the coexistence region. Inclusion of the swim pressure in the mechanical compressibility definition suggests that the interface is essential for determining phase behavior.

Intimate partner violence and muscularity-building behavior in latino sexual minority men.

Intimate partner violence (IPV) has been associated with increased prevalence of eating disorders. In men, disordered eating is often related to the muscularized ideal. Sexual minority men (SMM; e.g., gay, bisexual, etc.) are at higher risk for eating disorders and Latino SMM may be at particularly high risk; however, IPV and eating pathology has yet to be examined in this population. Therefore, the aim of this study is to elucidate the association between IPV and muscularity-related dissatisfaction and muscularity-oriented behavior in Latino SMM. Participants were 81 Latino SMM. Thirty participants (37% of the sample) met the cutoff score for experiencing IPV in the past month. In bivariate analyses, IPV was associated with muscularity-oriented behavior, but not muscularity-related dissatisfaction. In multivariable analyses, IPV was negatively associated with muscularity-related dissatisfaction with a small effect size and positively associated with muscularity-oriented behavior with a large effect size. It may be that SMM engage in muscle building behavior to increase self-esteem, regulate affect, or better physically protect themselves from their abusive partner. Future research should investigate motivation for muscle building behavior in individuals experiencing IPV.

Nonlinear microrheology of active Brownian suspensions.

The rheological properties of active suspensions are studied via microrheology: tracking the motion of a colloidal probe particle in order to measure the viscoelastic response of the embedding material. The passive probe particle with size R is pulled through the suspension by an external force Fext, which causes it to translate at some speed Uprobe. The bath is comprised of a Newtonian solvent with viscosity ηs and a dilute dispersion of active Brownian particles (ABPs) with size a, characteristic swim speed U0, and a reorientation time τR. The motion of the probe distorts the suspension microstructure, so the bath exerts a reactive force on the probe. In a passive suspension, the degree of distortion is governed by the Péclet number, Pe = Fext/(kBT/a), the ratio of the external force to the thermodynamic restoring force of the suspension. In active suspensions, however, the relevant parameter is Ladv/l = UprobeτR/U0τR∼Fext/Fswim, where Fswim = ζU0 is the swim force that propels the ABPs (ζ is the Stokes drag on a swimmer). When the external forces are weak, Ladv≪l, the autonomous motion of the bath particles leads to "swim-thinning," though the effective suspension viscosity is always greater than ηs. When advection dominates, Ladv≫l, we recover the familiar behavior of the microrheology of passive suspensions. The non-Newtonian behavior for intermediate values of Ladv/l is determined by l/Rc = U0τR/Rc-the ratio of the swimmer's run length l to the geometric length scale associated with interparticle interactions Rc = R + a. The results in this manuscript are approximate as they are based on numerical solutions to mean-field equations that describe the motion of the active bath particles.

Diffusion and flow in complex liquids.

Thermal motion of particles and molecules in liquids underlies many chemical and biological processes. Liquids, especially in biology, are complex due to structure at multiple relevant length scales. While diffusion in homogeneous simple liquids is well understood through the Stokes-Einstein relation, this equation fails completely in describing diffusion in complex media. Modeling, understanding, engineering and controlling processes at the nanoscale, most importantly inside living cells, requires a theoretical framework for the description of viscous response to allow predictions of diffusion rates in complex fluids. Here we use a general framework with the viscosity η(k) described by a function of wave vector in reciprocal space. We introduce a formulation that allows one to relate the rotational and translational diffusion coefficients and determine the viscosity η(k) directly from experiments. We apply our theory to provide a database for rotational diffusion coefficients of proteins/protein complexes in the bacterium E. coli. We also provide a database for the diffusion coefficient of proteins sliding along major grooves of DNA in E. coli. These parameters allow predictions of rate constants for association of proteins. In addition to constituting a theoretical framework for description of diffusion of probes and viscosity in complex fluids, the formulation that we propose should decrease substantially the cost of numerical simulations of transport in complex media by replacing the simulation of individual crowding particles with a continuous medium characterized by a wave-length dependent viscosity η(k).

Ligand binding to G-quadruplex DNA: new insights from ultraviolet resonance Raman spectroscopy.

G-Quadruplexes (G4s) are noncanonical nucleic acid structures involved in the regulation of several biological processes of many organisms. The rational design of G4-targeting molecules developed as potential anticancer and antiviral therapeutics is a complex problem intrinsically due to the structural polymorphism of these peculiar DNA structures. The aim of the present work is to show how Ultraviolet Resonance Raman (UVRR) spectroscopy can complement other techniques in providing valuable information about ligand/G4 interactions in solution. Here, the binding of BRACO-19 and Pyridostatin - two of the most potent ligands - to selected biologically relevant G4s was investigated by polarized UVRR scattering at 266 nm. The results give new insights into the binding mode of these ligands to G4s having different sequences and topologies by performing an accurate analysis of peaks assigned to specific groups and their changes upon binding. Indeed, the UVRR data not only show that BRACO-19 and Pyridostatin interact with different G4 sites, but also shed light on the ligand and G4 chemical groups really involved in the interaction. In addition, UVRR results complemented by circular dichroism data clearly indicate that the binding mode of a ligand can also depend on the conformation(s) of the target G4. Overall, these findings demonstrate the utility of using UVRR spectroscopy in the investigation of G4s and G4-ligand interactions in solution.

Syndemics and the PrEP Cascade: Results from a Sample of Young Latino Men Who Have Sex with Men.

Young Latino men who have sex with men (MSM) are a highly vulnerable population for HIV infection. Pre-exposure prophylaxis (PrEP) is a novel biomedical HIV prevention tool that may aid in reducing the disparity in HIV incidence among Latino MSM. However, PrEP use is disproportionally low among Latino MSM and, therefore, identifying barriers along the PrEP continuum of care (the "PrEP cascade") would provide insight into how to best deploy PrEP interventions. Syndemics theory is a prominent framework employed in HIV prevention; however, to date, no known studies have applied this theory to PrEP. Thus, the aim of the current study was to explore the association between syndemics and the PrEP cascade, including the degree to which psychosocial and structural syndemic constructs are related to the PrEP cascade. Participants were 151 young Latino MSM (M age = 24 years; SD = 3) residing in San Diego, California, who completed a battery of online self-report measures. Results indicated high levels of syndemic indicators and varying levels of engagement across the PrEP cascade. As syndemic indicators increased, the odds of engagement across the PrEP cascade were significantly lowered. Psychosocial and structural syndemic factors accounted for unique variance in the PrEP cascade. Results highlight the need for combination interventions that address both psychosocial and structural barriers to PrEP use and persistence among young Latino MSM.

Outcomes of noncardiotomy patients requiring postoperative extracorporeal membrane oxygenation.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in the postoperative period has expanded to include a variety of noncardiotomy procedures. It is important to investigate outcomes for this uniquely ill subset of patients as currently published data on this subject is limited. METHODS: All ECMO events at our institution from 2006 to 2017 were retrospectively considered. Patients were grouped into a postoperative noncardiotomy (PNC) cohort (n = 20) and a larger control cohort (n = 220). For additional analysis, the PNC cohort was further split into a liver transplant group (n = 4) and thoracic surgery group (n = 10). Basic demographics, medical history, type of operation performed, indication for support, and survival data were collected on all patients. Appropriate statistical analyses were performed and a P < .05 was considered statistically significant. RESULTS: Twenty PNC-ECMO patients were identified. The indications for support were respiratory failure, cardiac arrest, and cardiogenic shock. PNC patient survival was similar to our control cohort, as well as extracorporeal life support organization (ELSO) published data with 55% weaning off ECMO and 50% surviving to discharge. Twelve-month predicted survival was 40%. Post thoracic surgical patients were reviewed, and their survival rates were similar to the larger control cohort as well. There were no survivors in the liver transplant group. CONCLUSIONS: Despite recent noncardiotomy surgery, patients who required ECMO for salvage in the postoperative period showed similar outcomes compared to our larger cohort and to published ELSO data, and reasonable long-term survival outcomes. This suggests that ECMO may be applied to a variety of postoperative settings with outcomes on par with nationally published results.

Burkholderia cenocepacia H111 Produces a Water-Insoluble Exopolysaccharide in Biofilm: Structural Determination and Molecular Modelling.

Biofilms are a multicellular way of life, where bacterial cells are close together and embedded in a hydrated macromolecular matrix which offers a number of advantages to the cells. Extracellular polysaccharides play an important role in matrix setup and maintenance. A water-insoluble polysaccharide was isolated and purified from the biofilm produced by Burkholderia cenocepacia strain H111, a cystic fibrosis pathogen. Its composition and glycosidic linkages were determined using Gas-Liquid Chromatography-Mass Spectrometry (GLC-MS) on appropriate carbohydrate derivatives while its complete structure was unraveled by 1D and 2D NMR spectroscopy in deuterated sodium hydroxide (NaOD) aqueous solutions. All the collected data demonstrated the following repeating unit for the water-insoluble B. cenocepacia biofilm polysaccharide: [3)-α-d-Galp-(1→3)-α-d-Glcp-(1→3)-α-d-Galp-(1→3)-α-d-Manp-(1→]n Molecular modelling was used, coupled with NMR Nuclear Overhauser Effect (NOE) data, to obtain information about local structural motifs which could give hints about the polysaccharide insolubility. Both modelling and NMR data pointed at restricted dynamics of local conformations which were ascribed to the presence of inter-residue hydrogen bonds and to steric restrictions. In addition, the good correlation between NOE data and calculated interatomic distances by molecular dynamics simulations validated potential energy functions used for calculations.

Inter-residual Hydrogen Bonding in Carbohydrates Unraveled by NMR Spectroscopy and Molecular Dynamics Simulations.

Carbohydrates, also known as glycans in biological systems, are omnipresent in nature where they as glycoconjugates occur as oligo- and polysaccharides linked to lipids and proteins. Their three-dimensional structure is defined by two or three torsion angles at each glycosidic linkage. In addition, transglycosidic hydrogen bonding between sugar residues may be important. Herein we investigate the presence of these inter-residue interactions by NMR spectroscopy in D2 O/[D6 ]DMSO (70:30) or D2 O and by molecular dynamics (MD) simulations with explicit water as solvent for disaccharides with structural elements α-d-Manp-(1→2)-d-Manp, ß-d-GlcpNAc-(1→2)-d-Manp, and α-d-Glcp-(1→4)-ß-d-Glcp, all of which have been suggested to exhibit inter-residue hydrogen bonding. For the disaccharide ß-d-GlcpNAc-(1→2)-ß-d-Manp-OMe, the large extent of O5'⋅⋅⋅HO3 hydrogen bonding as seen from the MD simulation is implicitly supported by the 1 H NMR chemical shift and 3 JHO3,H3 value of the hydroxy proton. In the case of α-d-Glcp-(1→4)-ß-d-Glcp-OMe, the existence of a transglycosidic hydrogen bond O2'⋅⋅⋅HO3 was proven by the presence of a cross-peak in 1 H,13 C HSQC-TOCSY experiments as a result of direct TOCSY transfer between HO3 of the reducing end residue and H2' (detected at C2') of the terminal residue. The occurrence of inter-residue hydrogen bonding, albeit transient, is judged important for the stabilization of three-dimensional structures, which may be essential in maintaining a conformational state for carbohydrate-protein interactions of glycans to take place in biologically important environments.