Ion size effects at ionic exclusion from dielectric interfaces and slit nanopores

A previously developed field-theoretic model [R.D. Coalson et al., J. Chem. Phys. 102, 4584 (1995)] that treats core collisions and Coulomb interactions on the same footing is investigated in order to understand ion size effects on the partition of neutral and charged particles at planar interfaces and the ionic selectivity of slit nanopores. We introduce a variational scheme that can go beyond the mean-field (MF) regime and couple in a consistent way pore modified core interactions, steric effects, electrostatic solvation and image-charge forces, and surface charge induced electrostatic potential. We show that in the dilute limit, the MF and the variational theories agree well with MC simulation results, in contrast to a recent RPA method. The partition of charged Yukawa particles at a neutral dielectric interface (e.g air-water or protein-water interface) is investigated. It is shown that as a result of the competition between core collisions that push the ions towards the surface, and repulsive solvation and image forces that exclude them from the interface, a concentration peak of finite size ions sets in close to the dielectric interface. We also characterize the role played by the ion size on the ionic selectivity of neutral slit nanopores. We show that the complex interplay between electrostatic forces, excluded volume effects induced by core collisions and steric effects leads to an unexpected reversal in the ionic selectivity of the pore with varying pore size: while large pores exhibits a higher conductivity for large ions, narrow pores exclude large ions more efficiently than small ones

Diffuse-Charge Dynamics in Electrochemical Systems

The response of a model micro-electrochemical system to a time-dependent applied voltage is analyzed. The article begins with a fresh historical review including electrochemistry, colloidal science, and microfluidics. The model problem consists of a symmetric binary electrolyte between parallel-plate, blocking electrodes which suddenly apply a voltage. Compact Stern layers on the electrodes are also taken into account. The Nernst-Planck-Poisson equations are first linearized and solved by Laplace transforms for small voltages, and numerical solutions are obtained for large voltages. The ``weakly nonlinear'' limit of thin double layers is then analyzed by matched asymptotic expansions in the small parameter $\epsilon = \lambda_D/L$, where $\lambda_D$ is the screening length and $L$ the electrode separation. At leading order, the system initially behaves like an RC circuit with a response time of $\lambda_D L / D$ (not $\lambda_D^2/D$), where $D$ is the ionic diffusivity, but nonlinearity violates this common picture and introduce multiple time scales. The charging process slows down, and neutral-salt adsorption by the diffuse part of the double layer couples to bulk diffusion at the time scale, $L^2/D$. In the ``strongly nonlinear'' regime (controlled by a dimensionless parameter resembling the Dukhin number), this effect produces bulk concentration gradients, and, at very large voltages, transient space charge. The article concludes with an overview of more general situations involving surface conduction, multi-component electrolytes, and Faradaic processes.Comment: 10 figs, 26 pages (double-column), 141 reference

Intercomparison of shortwave radiative transfer schemes in global aerosol modeling: results from the AeroCom Radiative Transfer Experiment

In this study we examine the performance of 31 global model radiative transfer schemes in cloud-free conditions with prescribed gaseous absorbers and no aerosols (Rayleigh atmosphere), with prescribed scattering-only aerosols, and with more absorbing aerosols. Results are compared to benchmark results from high-resolution, multi-angular line-by-line radiation models. For purely scattering aerosols, model bias relative to the line-by-line models in the top-of-the atmosphere aerosol radiative forcing ranges from roughly −10 to 20%, with over- and underestimates of radiative cooling at lower and higher solar zenith angle, respectively. Inter-model diversity (relative standard deviation) increases from ~10 to 15% as solar zenith angle decreases. Inter-model diversity in atmospheric and surface forcing decreases with increased aerosol absorption, indicating that the treatment of multiple-scattering is more variable than aerosol absorption in the models considered. Aerosol radiative forcing results from multi-stream models are generally in better agreement with the line-by-line results than the simpler two-stream schemes. Considering radiative fluxes, model performance is generally the same or slightly better than results from previous radiation scheme intercomparisons. However, the inter-model diversity in aerosol radiative forcing remains large, primarily as a result of the treatment of multiple-scattering. Results indicate that global models that estimate aerosol radiative forcing with two-stream radiation schemes may be subject to persistent biases introduced by these schemes, particularly for regional aerosol forcing

Equivalence of ELISpot Assays Demonstrated between Major HIV Network Laboratories

The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC-VIMC) was created to provide standardized immunogenicity monitoring services for HIV vaccine trials. The ex vivo interferon-gamma (IFN-γ) ELISpot is used extensively as a primary immunogenicity assay to assess T cell-based vaccine candidates in trials for infectious diseases and cancer. Two independent, GCLP-accredited central laboratories of CTC-VIMC routinely use their own standard operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine trials. Studies are imperatively needed to assess the comparability of ELISpot measurements across laboratories to benefit optimal advancement of vaccine candidates.We describe an equivalence study of the two independently qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent analysis were managed by independent statisticians to avoid subjectivity. The equivalence of both response rates and positivity calls to a given stimulus was assessed based on pre-specified acceptance criteria derived from a separate pilot study.Detection of positive responses was found to be equivalent between both laboratories. The 95% C.I. on the difference in response rates, for CMV (-1.5%, 1.5%) and CEF (-0.4%, 7.8%) responses, were both contained in the pre-specified equivalence margin of interval [-15%, 15%]. The lower bound of the 95% C.I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC central laboratory already using one of the two SOPs also showed comparability when tested in a smaller sub-study.The described study procedure provides a prototypical example for the comparison of bioanalytical methods in HIV vaccine and other disease fields. This study also provides valuable and unprecedented information for future vaccine candidate evaluations on the comparison and pooling of ELISpot results generated by the CTC-VIMC central core laboratories

Solvation free energy profile of the SCN- ion across the water-1,2-dichloroethane liquid/liquid interface. A computer simulation study

The solvation free energy profile of a single SCN- ion is calculated across the water-1,2-dichloroethane liquid/liquid interface at 298 K by the constraint force method. The obtained results show that the free energy cost of transferring the ion from the aqueous to the organic phase is about 70 kJ/mol, The free energy profile shows a small but clear well at the aqueous side of the interface, in the subsurface region of the water phase, indicating the ability of the SCN- ion to be adsorbed in the close vicinity of the interface. Upon entrance of the SCN- ion to the organic phase a coextraction of the water molecules of its first hydration shell occurs. Accordingly, when it is located at the boundary of the two phases the SCN- ion prefers orientations in which its bulky S atom is located at the aqueous side, and the small N atom, together with its first hydration shell, at the organic side of the interface

In Vitro Aggregation Behavior of a Non-Amyloidogenic λ Light Chain Dimer Deriving from U266 Multiple Myeloma Cells

Excessive production of monoclonal light chains due to multiple myeloma can induce aggregation-related disorders, such as light chain amyloidosis (AL) and light chain deposition diseases (LCDD). In this work, we produce a non-amyloidogenic IgE λ light chain dimer from human mammalian cells U266, which originated from a patient suffering from multiple myeloma, and we investigate the effect of several physicochemical parameters on the in vitro stability of this protein. The dimer is stable in physiological conditions and aggregation is observed only when strong denaturating conditions are applied (acidic pH with salt at large concentration or heating at melting temperature Tm at pH 7.4). The produced aggregates are spherical, amorphous oligomers. Despite the larger β-sheet content of such oligomers with respect to the native state, they do not bind Congo Red or ThT. The impossibility to obtain fibrils from the light chain dimer suggests that the occurrence of amyloidosis in patients requires the presence of the light chain fragment in the monomer form, while dimer can form only amorphous oligomers or amorphous deposits. No aggregation is observed after denaturant addition at pH 7.4 or at pH 2.0 with low salt concentration, indicating that not a generic unfolding but specific conformational changes are necessary to trigger aggregation. A specific anion effect in increasing the aggregation rate at pH 2.0 is observed according to the following order: SO4−≫Cl−>H2PO4−, confirming the peculiar role of sulfate in promoting protein aggregation. It is found that, at least for the investigated case, the mechanism of the sulfate effect is related to protein secondary structure changes induced by anion binding

A parameter-free total Lagrangian smooth particle hydrodynamics algorithm applied to problems with free surfaces

This paper presents a new Smooth Particle Hydrodynamics computational framework for the solution of inviscid free surface flow problems. The formulation is based on the Total Lagrangian description of a system of first-order conservation laws written in terms of the linear momentum and the Jacobian of the deformation. One of the aims of this paper is to explore the use of Total Lagrangian description in the case of large deformations but without topological changes. In this case, the evaluation of spatial integrals is carried out with respect to the initial undeformed configuration, yielding an extremely efficient formulation where the need for continuous particle neighbouring search is completely circumvented. To guarantee stability from the SPH discretisation point of view, consistently derived Riemann-based numerical dissipation is suitably introduced where global numerical entropy production is demonstrated via a novel technique in terms of the time rate of the Hamiltonian of the system. Since the kernel derivatives presented in this work are fixed in the reference configuration, the non-physical clumping mechanism is completely removed. To fulfil conservation of the global angular momentum, a posteriori (least-squares) projection procedure is introduced. Finally, a wide spectrum of dedicated prototype problems is thoroughly examined. Through these tests, the SPH methodology overcomes by construction a number of persistent numerical drawbacks (e.g. hour-glassing, pressure instability, global conservation and/or completeness issues) commonly found in SPH literature, without resorting to the use of any ad-hoc user-defined artificial stabilisation parameters. Crucially, the overall SPH algorithm yields equal second order of convergence for both velocities and pressure

Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity.

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution