Diffusioosmotic flow reversals due to ion-ion electrostatic correlations.

Existing theories of diffusioosmosis have neglected ion-ion electrostatic correlations, which are important in concentrated electrolytes. Here, we develop a mathematical model to numerically compute the diffusioosmotic mobilities of binary symmetric electrolytes across low to high concentrations in a charged parallel-plate channel. We use the modified Poisson equation to model the ion-ion electrostatic correlations and the Bikerman model to account for the finite size of ions. We report two key findings. First, ion-ion electrostatic correlations can cause a unique reversal in the direction of diffusioosmosis. Such a reversal is not captured by existing theories, occurs at ≈ 0.4 M for a monovalent electrolyte, and at a much lower concentration of ≈ 0.003 M for a divalent electrolyte in a channel with the same surface charge. This highlights that diffusioosmosis of a concentrated electrolyte can be qualitatively different from that of a dilute electrolyte, not just in its magnitude but also its direction. Second, we predict a separate diffusioosmotic flow reversal, which is not due to electrostatic correlations but the competition between the underlying chemiosmosis and electroosmosis. This reversal can be achieved by varying the magnitude of the channel surface charge without changing its sign. However, electrostatic correlations can radically change how this flow reversal depends on the channel surface charge and ion diffusivity between a concentrated and a dilute electrolyte. The mathematical model developed here can be used to design diffusioosmosis of dilute and concentrated electrolytes, which is central to applications such as species mixing and separation, enhanced oil recovery, and reverse electrodialysis.

A Quantum Double-or-Nothing Game: An Application of the Kelly Criterion to Spins.

A quantum game is constructed from a sequence of independent and identically polarised spin-1/2 particles. Information about their possible polarisation is provided to a bettor, who can wager in successive double-or-nothing games on measurement outcomes. The choice at each stage is how much to bet and in which direction to measure the individual particles. The portfolio's growth rate rises as the measurements are progressively adjusted in response to the accumulated information. Wealth is amassed through astute betting. The optimal classical strategy is called the Kelly criterion and plays a fundamental role in portfolio theory and consequently quantitative finance. The optimal quantum strategy is determined numerically and shown to differ from the classical strategy. This paper contributes to the development of quantum finance, as aspects of portfolio optimisation are extended to the quantum realm. Intriguing trade-offs between information gain and portfolio growth are described.

Dynamics of technology emergence in innovation networks.

To create the next innovative product, participants in science need to understand which existing technologies can be combined, what new science must be discovered, and what new technologies must be invented. Knowledge of these often arrives by means of expert consensus or popularity metrics, masking key information on how intellectual efforts accumulate into technological progress. To address this shortcoming, we first present a method to establish a mathematical link between technological evolution and complex networks: a path of events that narrates innovation bottlenecks. Next, we quantify the position and proximity of documents to these innovation paths. The result is an innovation network that more exhaustively captures deterministic knowledge flows with respect to a marketed innovative product. Our dataset, containing over three million biomedical citations, demonstrates the possibility of quantifying the accumulation, speed, and division of labour in innovation over a sixty-year time horizon. The significance of this study includes the (i) use of a purpose-generated dataset showing causal paths from research to development to product; (ii) analysis of the innovation process as a directed acyclic graph; (iii) comparison between calendar time and network time; (iv) ordering of science funders along technology lifecycles; (v) quantification of innovative activities' importance to an innovative outcome; and (vi) integration of publication, patent, clinical trial, regulatory data to study innovation holistically.

Unidirectional drying of a suspension of diffusiophoretic colloids under gravity.

Recent experiments (K. Inoue and S. Inasawa, RSC Adv., 2020, 10, 15763-15768) and simulations (J.-B. Salmon and F. Doumenc, Phys. Rev. Fluids, 2020, 5, 024201) demonstrated the significant impact of gravity on unidirectional drying of a colloidal suspension. However, under gravity, the role of colloid transport induced by an electrolyte concentration gradient, a mechanism known as diffusiophoresis, is unexplored to date. In this work, we employ direct numerical simulations and develop a macrotransport theory to analyze the advective-diffusive transport of an electrolyte-colloid suspension in a unidirectional drying cell under the influence of gravity and diffusiophoresis. We report three key findings. First, drying a suspension of solute-attracted diffusiophoretic colloids causes the strongest phase separation and generates the thinnest colloidal layer compared to non-diffusiophoretic or solute-repelled colloids. Second, when colloids are strongly solute-repelled, diffusiophoresis prevents the formation of colloid concentration gradient and hence gravity has a negligible effect on colloidal layer formation. Third, our macrotransport theory predicts new scalings for the growth of the colloidal layer. The scalings match with direct numerical simulations and indicate that the colloidal layer produced by solute-repelled diffusiophoretic colloids could be an order of magnitude thicker compared to non-diffusiophoretic or solute-attracted colloids. Our results enable tailoring the separation of colloid-electrolyte suspensions by tuning the interactions between the solvent, electrolyte, and colloids under Earth's or microgravity, which is central to ground-based and in-space applications.

Diffusiophoresis of a spherical particle in porous media.

Recent experiments by Doan et al. (Nano Lett., 2021, 21, 7625-7630) demonstrated and measured colloid diffusiophoresis in porous media but existing theories cannot predict the observed colloid motion. Here, using regular perturbation method, we develop a mathematical model that can predict the diffusiophoretic motion of a charged colloidal particle driven by a binary monovalent electrolyte concentration gradient in a porous medium. The porous medium is modeled as a Brinkman medium with a constant Darcy permeability. The linearized Poisson-Boltzmann equation is employed to model the equilibrium electric potential distribution that is driven out-of-equilibrium under diffusiophoresis. We report three key findings. First, we demonstrate that colloid diffusiophoresis could be drastically hindered in a porous medium due to the additional hydrodynamic drag compared to diffusiophoresis in a free electrolyte solution. Second, we show that the variation of the diffusiophoretic motion with respect to a change in the electrolyte concentration in a porous medium could be qualitatively different from that in a free electrolyte solution. Third, our results match quantitatively with experimental measurements, highlighting the predictive power of the present model. The mathematical model developed here could be employed to design diffusiophoretic colloid transport in porous media, which are central to applications such as nanoparticle drug delivery and enhanced oil recovery.

Tuning chemotactic and diffusiophoretic spreading via hydrodynamic flows.

The transport of microorganisms by chemotaxis is described by the same "log-sensing" response as colloids undergoing diffusiophoresis, despite their different mechanistic origins. We employ a recently-developed macrotransport theory to analyze the advective-diffusive transport of a chemotactic or diffusiophoretic colloidal species (both referred to as "colloids") in a circular tube under a steady pressure-driven flow (referred to as hydrodynamic flow) and transient solute gradient. First, we derive an exact solution to the log-sensing chemotactic/diffusiophoretic macrotransport equation. We demonstrate that a strong hydrodynamic flow can reduce spreading of solute-repelled colloids, by eliminating super-diffusion which occurs in an otherwise quiescent system. In contrast, hydrodynamic flows always enhance spreading of solute-attracted colloids. Second, we generalize the exact solution to show that the above tunable spreading phenomena by hydrodynamic flows persist quantitatively for decaying colloids, as may occur with cell death, for example. Third, we examine the spreading of chemotactic colloids by employing a more general model that captures a hallmark of chemotaxis, that log-sensing occurs only over a finite range of solute concentration. Apart from demonstrating for the first time the generality of the macrotransport theory to incorporate an arbitrary chemotactic flow model, we reveal via numerical solutions new regimes of anomalous spreading, which match qualitatively with experiments and are tunable by hydrodynamic flows. The results presented here could be employed to tailor chemotactic/diffusiophoretic colloid transport using hydrodynamic flows, which are central to applications such as oil recovery and bioremediation of aquifers.

HDX-MS for Epitope Characterization of a Therapeutic ANTIBODY Candidate on the Calcium-Binding Protein Annexin-A1.

Annexin-A1 (ANXA1) belongs to a class of highly homologous Ca2+-dependent phospholipid-binding proteins. Its structure consists of a core region composed of four homologous repeats arranged in a compact, hydrolysis-resistant structure and an N-terminal region with a Ca2+-dependent conformation. ANXA1 is involved in several processes, including cell proliferation, apoptosis, metastasis, and the inflammatory response. Therefore, the development of antibodies blocking selected regions on ANXA1 holds great potential for the development of novel therapeutics treating inflammatory and cancer diseases. Here, we report the interaction site between an ANXA1-specific antibody known to inhibit T cell activation without adverse cytotoxic effects and ANXA1 using amide hydrogen-deuterium exchange mass spectrometry (HDX-MS). For the epitope determination, we applied two bottom-up HDX-MS approaches with pepsin digestion in solution and immobilized on beads. Both strategies revealed the interaction region within domain III of ANXA1 in Ca2+-bound conformation. The antibody-binding region correlates with the hydrophobic binding pocket of the N-terminal domain formed in the absence of calcium. This study demonstrates that even cryptic and flexible binding regions can be studied by HDX-MS, allowing a fast and efficient determination of the binding sites of antibodies which will help to define a mode of action profile for their use in therapy.

Surfactant Driven Marangoni Spreading in the Presence of Predeposited Insoluble Surfactant Monolayers.

When an insoluble surfactant is deposited on the surface of a thin fluid film, stresses induced by surface tension gradients drive Marangoni spreading across the subphase surface. The presence of a predeposited layer of an insoluble surfactant alters that spreading. In this study, the fluid film was aqueous, the predeposited insoluble surfactant was dipalmitoylphosphatidylcholine (DPPC), and the deposited insoluble surfactant was oleic acid. An optical density-based method was used to measure subphase surface distortion, called the Marangoni ridge, associated with propagation of the spreading front. The movement of the Marangoni ridge was correlated with movement of surface tracer particles that indicated both the boundary between the two surfactant layers and the surface fluid velocities. As the deposited oleic acid monolayer spread, it compressed the predeposited DPPC monolayer. During spreading, the surface tension gradient extended into the predeposited monolayer, which was compressed nonuniformly, from the deposited monolayer. The spreading was so rapid that the compressed predeposited surfactant could not have been in quasi-equilibrium states during the spreading. As the initial concentrations of the predeposited surfactant were increased, the shape of the Marangoni ridge deformed. When the initial concentration of the predeposited surfactant reached about 70 A2/molecule, there was no longer a Marangoni ridge but rather a broadly distributed excess of fluid above the initial fluid height. The nonuniform compression of the annulus of the predeposited monolayer also caused tangential motion ahead of both the Marangoni ridge and the boundary between the two monolayers. Spreading ceased when the two monolayers reached the same final surface tension. The final area per molecule of the DPPC monolayer matched that expected from the equilibrium DPPC isotherm at the same final surface tension. Thus, at the end of spreading, there was a simple surface tension balance between the two distinct monolayers.

Advective-diffusive spreading of diffusiophoretic colloids under transient solute gradients.

We analytically calculate the one-dimensional advective-diffusive spreading of a point source of diffusiophoretic (DP) colloids, driven by the simultaneous diffusion of a Gaussian solute patch. The spreading of the DP colloids depends critically on the ratio of the DP mobility, M (which can be positive or negative), to the solute diffusivity, Ds. For instance, we demonstrate, for the first time, that solute-repelling colloids (M < 0) undergo long-time super-diffusive transport for M/Ds < -1. In contrast, the spreading of strongly solute-attracting colloids (M/Ds≫ 1) can be spatially arrested over long periods on the solute diffusion timescale, due to a balance between colloid diffusion and DP under the evolving solute gradient. Further, a patch of the translating solute acts as a "shuttle" that rapidly transports the colloids relative to their diffusive timescale. Finally, we use numerical computations to show that the above behaviors persist for three-dimensional, radially symmetric DP spreading. The results presented here could guide the use of DP colloids for microscale particle sorting, deposition, and delivery.

Toward a nonequilibrium Stokes-Einstein relation via active microrheology of hydrodynamically interacting colloidal dispersions.

We derive a theoretical model for the nonequilibrium stress in a flowing colloidal suspension by tracking the motion of a single embedded probe. While Stokes-Einstein relations connect passive, observable diffusion of a colloidal particle to properties of the suspending medium, they are limited to linear response. Actively forcing a probe through a suspension produces nonequilibrium stress that at steady state can be related directly to observable probe motion utilizing an equation of motion rather than an equation of state, giving a nonequilibrium Stokes-Einstein relation [J. Rheol., 2012, 56, 1175-1208]. Here that freely-draining theory is expanded to account for hydrodynamic interactions. To do so, we construct an effective hydrodynamic resistance tensor, through which the particle flux is projected to give the advective and diffusive components of a Cauchy momentum balance. The resultant phenomenological relation between suspension stress, viscosity and diffusivity is a generalized nonequilibrium Stokes-Einstein relation. The phenomenological model is compared with the statistical mechanics theory for dilute suspensions as well as dynamic simulation at finite concentration which show good agreement, indicating that the suspension stress, viscosity, and force-induced diffusion in a flowing colloidal dispersion can be obtained simply by tracking the motion of a single Brownian probe.

Directed immobilization of reduced antibody fragments onto a novel SAM on gold for myoglobin impedance immunosensing.

The successful construction of an immunosensor depends on having an effective procedure for immobilising the bio-recognition element to the transducer surface. In the present study, an amino-terminated 4-aminothiophenol (ATP) self-assembled monolayer (SAM) was modified with heterobifunctional crosslinker sulfosuccinimidyl 4-[N-maleimidomethyl] cyclohexane-1-carboxylate to couple reduced anti-myoglobin half-antibody fragments. The disulphide groups present in the hinge region of IgG molecules were selectively cleaved by 2-mercaptoethylamine to produce reduced half-antibody fragments with free sulphydryl groups. The maleimide terminated 4-ATP SAM modified surface was coupled to these reduced antibody fragments to produce highly oriented immobilization of the half-antibody via its Fc domain and to allow free access to the Fv bindings sites. This represents an improvement by comparison with biotin/avidin mediated IgG attachment which is essentially randomly oriented. Functional immunosensors were able to detect myoglobin in both phosphate buffered saline and whole serum over the range of concentrations from 10(-13)M to 10(-6)M, and order of magnitude better than avidin/biotin linked immunosensors. In addition, atomic force microscopy (AFM) was carried out to elucidate the nanotopology of the immunosensor surface at different stages of fabrication; the images demonstrate that half antibodies bind as described and show structural changes on subsequent antigen binding.

Exercise-induced desaturation and electrocardiogram changes in people with severe lung disease: an exploratory investigation of 25 serial cases.

BACKGROUND: Arterial desaturation is a commonly accepted clinical basis for discontinuing physical activity in people with chronic obstructive pulmonary disease. OBJECTIVE: The purpose of this exploratory study was to examine the electrocardiograms of people with severe chronic obstructive pulmonary disease recovering from exercise-induced arterial desaturation. SUBJECTS: Subjects (n = 25) walked for 6 minutes while oxygen saturation was monitored. METHODS: When the Spo2 decreased below 90%, subjects were asked to sit and rest while the electrocardiograms were recorded. For all patients, Spo2 decreased 11.6% on average below baseline during walking. Four patients developed dysrhythmias during desaturation, with a mean lowest Spo2 of 85%. The Spo2 in six other patients continued to decrease below 80% despite rest, yet these patients did not develop new dysrhythmias. CONCLUSIONS: Our findings suggest that a decrease in Spo2 during exercise does not necessarily correlate with cardiac rhythm.

A novel and convenient self-drying system for bacterial preservation.

An effective microbial preservation technology for the long-term storage of viable prokaryotic cells is described. The method combines an almost instantaneous drying step with minimal stress to the cells during drying to maximize survival on rehydration. This is achieved by contact of a microlitre aliquot of a bacterial suspension with a novel, pre-dried activated charcoal cloth based matrix contained within a re-sealable system that can then be stored. The simple methodology completely circumvents the requirement for further drying or preparation. Using this method, a standard laboratory Escherichia coli strain was successfully revived following 390 days storage at 4, 20 and 30 degrees C. Data obtained yielded approximately 20%, 6% and 0.1% viable organisms at the aforementioned temperatures, respectively, following initial inoculations of 1.1 x 10(8)/microl cells. While these figures represent a significant viability loss, there is sufficient recovery of microorganisms required for maintaining culture collections.

Separation of the insecticidal pyrethrin esters by capillary electrochromatography.

A simple, rapid technique for the direct separation and quantification of the six insecticidally active pyrethrin esters in typical extracts and commercial formulations by capillary electrochromatography (CEC) has been described. The separation of the pyrethrin esters was achieved by optimizing several parameters including the length of stationary phase, the mobile phase composition and column temperature. The mobile phase composition had the most pronounced effect toward resolving these structurally similar compounds. A ternary mobile phase composed of acetonitrile-aqueous buffer-tetrahydrofuran (55:35:10) provided the elutropic solvent strength needed to resolve the six esters from an extract mixture in under 16 min. A 25 cm packed bed of Hypersil 3 microm C18 stationary phase was used with the ternary mobile phase at 25 degrees C and 30 kV voltage. These conditions also yielded excellent separation of the pyrethrin esters in two different commercially available insecticidal formulations. In addition, the developed CEC method was shown to be a fast and easy way of quantifying the amount of these esters in typical pyrethrin formulations.

Separation of tocopherol isomers using capillary electrochromatography: comparison of monomeric and polymeric C30 stationary phases.

The comparison of tocopherol isomer separation achieved using different stationary-phase alkyl chain lengths (i.e., C18 vs C30) and modes of alkyl phase attachment to the silica-based supports (i.e., polymeric vs monomeric synthesis) using capillary electrochromatography (CEC) has been demonstrated. The smaller alkyl chain does not exhibit the shape selectivity needed to resolve all of the tocopherol isomers. Conversely, both polymeric and monomeric C30 phases show increased tocopherol isomer selectivity. Changing the elutropic strength of the mobile phase had dramatic effects on the selectivity, with small additions of water to a methanol mobile phase yielding the best selectivity. The complete baseline separation of the tocopherol isomers was achieved using the monomerically bound C30 stationary phase and a methanol/ water mobile phase. The differences in stationary-phase selectivity were examined using a NIST standard reference material for determining column selectivity in LC. The results indicated that the monomeric C30 actually had "intermediate" phase characteristics (i.e., high phase loading, end capping, etc). This new CEC-based separation was also used to separate the tocopherols in a vitamin E supplement sample.

Capillary electrochromatography of cholesterol and its ester derivatives.

Separation of cholesterol and its ester derivatives using micellar electrokinetic chromatography is a challenge due to the extreme hydrophobicity of these compounds. In this work, an isocratic capillary electrochromatography (CEC) method has been developed to separate a complex mixture of cholesterol and its 12-ester derivatives. The proportions of mobile phase (tetrahydrofuran, acetonitrile, water), as well as the effects of acid modifiers, buffer concentrations, voltage, and temperature on the separation of cholesterol derivatives were investigated. Addition of a polymeric surfactant, poly(sodium N-undecanoyl-L-glycinate), to the mobile phase reduced migration time and improved resolution of the analytes. The CEC method developed allows baseline separation of a complex mixture of cholesterol and 12 ester derivatives in less than 40 min. Finally, the method is applied to the characterization of cholesterol, cholesterol linoleate, and cholesterol oleate extracted from atherosclerotic plaque deposits in the arterial walls of a human aorta.

Separation of natural pyrethrum extracts using micellar electrokinetic chromatography.

The separation of the six pyrethrin esters in a technical pyrethrum extract (Riedel-de-Haën, Cresent Chemical Co. Inc. Hauppauge, NY, USA) by micellar electrokinetic chromatography (MEKC) using both sodium dodecyl sulfate (SDS) and a polymerized surfactant as pseudo-stationary phases has been investigated and optimized. Parameters such as pH, SDS and polymerized sodium N-undecyl sulfate (poly-SUS) concentration, type and concentration of background electrolyte and organic modifier, as well as the acetonitrile/water ratio in the sample were studied to optimize the resolution, efficiency, and analysis time. An optimized separation of the six pyrethrin esters was achieved in 25 min with 25 mM Tris, buffered at pH 9, containing 30 mM SDS, 25% (v/v) acetonitrile, and an equal volume ratio of acetonitrile/water sample matrix at a voltage of 25 kV. The use of 0.5% (w/v) poly-SUS enhanced resolution of the pyrethrin esters and shortened the total analysis time from 25 to 20 min, compared to the SDS mediated separation. The optimized MEKC results are compared to the HPLC separation of these esters and show an improvement in efficiency and total analysis time.

NMR and molecular mechanics study of pyrethrins I and II.

Bioassay-directed fractionation of the organic extract of the Kenyan pyrethrum flowers (Chrysanthemum cinerariaefolium Vissiani) resulted in the isolation of two natural pyrethrin esters, pyrethrin I (PI) and pyrethrin II (PII) as the major constituents. These esters elicited inhibition of the multiple drug resistant (MDR) Mycobacterium tuberculosis. The high-field (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of PI and PII were unequivocally assigned using modern two-dimensional (2D) proton-detected heteronuclear multiple-quantum coherence (HMQC) and heteronuclear multiple-bond correlation (HMBC) experiments. The conformations of both esters were deduced from (1)H-(1)H vicinal coupling constants and confirmed by 2D nuclear Overhauser effect spectroscopy (NOESY). Computer molecular modeling (MM) studies revealed that PI and PII molecules adopt a "love-seat" conformation in chloroform (CDCl(3)) solution.

Comparison of various antigens and their ability to detect protective antibodies against Pasteurella multocida using enzyme-linked immunosorbent assay.

Various antigenic extracts of the CU strain of Pasteurella multocida were prepared to determine their suitability as plate antigens for use in the enzyme-linked immunosorbent assay (ELISA) for the detection of fowl cholera antibodies. Antisera from two separate broiler breeder flocks with known fowl-cholera-vaccination histories were collected just before the birds were challenged with virulent strain X-73 P. multocida. A potassium thiocyanate (KSCN)-extracted antigen, a capsular (CAP) antigen, a lipopolysaccharide-protein antigen, and heat-stable, salt-soluble antigen were all suitable as ELISA plate-coating antigens. Filtered and unfiltered sonicates of the CU strain of P. multocida were also suitable ELISA plate antigens. The results suggested that different plate antigens were detecting different populations of antibodies formed in response to fowl cholera vaccinations. When antibody titers were correlated with survival after challenge, the KSCN and the CAP plate antigens placed more nonsurvivors into low-antibody-titer ranges and more survivors (protected birds) into the high-antibody-titer ranges than the other plate antigens.

The results of valve replacement for mitral valve prolapse.

Between January, 1975, and December, 1982, 33 patients underwent mitral valve replacement for mitral valve prolapse secondary to myxomatous degeneration. The majority were in the seventh decade of life (median age, 62 years), and all were seen with symptoms of mitral regurgitation. Echocardiography was more accurate in making the diagnosis of mitral valve prolapse more often (75%) than angiography (66%). Thirty-eight percent of the patients who underwent cineangiography had concomitant coronary artery disease and had coronary artery bypass grafting as well as mitral valve replacement. There was 1 operative death, an operative mortality of 3%. There were 6 late deaths, a late mortality of 18%. Of the 26 long-term survivors, 23 (88%) were in New York Heart Association Functional Class I and 3 (12%) were in Class II. The average length of follow-up was 33.25 months, and the 5-year actuarial survival was 76%. There was only one incident of thromboembolism (3%). Short-term and long-term survival were not related to the severity of mitral regurgitation but to the status of the left ventricle and the overall condition of the patient. These data suggest that older patients with severe mitral regurgitation secondary to mitral valve prolapse can undergo valve replacement with low operative mortality and gratifying long-term results.