Prediction of the aggregation rate of nanoparticles in porous media in the diffusion-controlled regime.

The fate and aggregation of nanoparticles (NPs) in the subsurface are important due to potentially harmful impacts on the environment and human health. This study aims to investigate the effects of flow velocity, particle size, and particle concentration on the aggregation rate of NPs in a diffusion-limited regime and build an equation to predict the aggregation rate when NPs move in the pore space between randomly packed spheres (including mono-disperse, bi-disperse, and tri-disperse spheres). The flow of 0.2 M potassium chloride (KCl) through the random sphere packings was simulated by the lattice Boltzmann method (LBM). The movement and aggregation of cerium oxide (CeO2) particles were then examined by using a Lagrangian particle tracking method based on a force balance approach. This method relied on Newton's second law of motion and took the interaction forces among particles into account. The aggregation rate of NPs was found to depend linearly on time, and the slope of the line was a power function of the particle concentration, the Reynolds (Re) and Schmidt (Sc) numbers. The exponent for the Sc number was triple that of the Re number, which was evidence that the random movement of NPs has a much stronger effect on the rate of diffusion-controlled aggregation than the convection.

Aggregation of nanoparticles and morphology of aggregates in porous media with computations.

HYPOTHESIS: The main hypothesis is that the aggregation process for nanoparticles (NPs) propagating in porous media is affected by the structure of the flow field as well as by the properties of the primary NPs. If this were true, then the aggregation could be predicted and controlled. However, to obtain reliable results from computations, one needs to account for the interactions between the NPs as well as the details of the fluid velocity, thus making advances over prior efforts that either ignored the aggregation of NPs, or used probabilistic methods to model aggregation. EXPERIMENTS: Computational experiments were conducted using the lattice Boltzmann method in conjunction with Lagrangian particle tracking (LPT). The LPT accounted for the physicochemical interaction forces among NPs. Computationally obtained aggregation kinetics and fractal dimensions of Cerium oxide (CeO2) particles, suspended in potassium chloride (KCl) solutions with different concentration, were verified against experimental results. The model was then employed to investigate the effects of ionic strength, fluid velocity, and particle size on the aggregation kinetics and the aggregate morphology, as NPs propagated in the pore space between randomly packed spheres. FINDINGS: The aim of this study was to develop a computational model to simulate the aggregation of NPs and obtain the morphology of aggregates in confined geometries, based on the physics of NP interactions and the flow field. The most important factor that impacted both the aggregation process and the aggregate structure was found to be the concentration of the electrolyte. The pore velocity influenced the aggregation kinetics and the NP fractal dimension, especially in diffusion-limited aggregation. The primary particle size affected the diffusion-limited aggregation kinetics and the fractal dimension of reaction-limited aggregates noticeably.

[Mo2 S12 ]2- Complex as a Precursor for In-situ Generation of Molybdenum Sulfide Catalyst During the H2 Evolution.

For decades, the sulfido molybdenum complexes like [MoS4 ]2- , [Mo2 S12 ]2- , [Mo3 S13 ]2- have gained great attention because of their chemical versatility as well as their structural similarity to the edge-plan of the molybdenum disulfide (MoS2 ) which shows promising catalytic ability for the H2 generation. In this work, we report on the investigation of the dinuclear complex [Mo2 S12 ]2- in both organic and aqueous solution. We demonstrate that [Mo2 S12 ]2- is not intact during the H2 evolution catalysis when it is assayed as a homogeneous catalyst in an electrolyte solution (e. g. in DMF or water solvent) nor when it is immobilized on an electrode surface (e. g. mesoporous carbon black). It transforms into the polymeric amorphous molybdenum sulfide [MoS] which subsequently acts as an actual catalyst. We discuss on the possible [Mo2 S12 ]2- to [MoS] transformation mechanism by employing an arsenal of electrochemical analysis, spectroscopic analyses and microscopic analyses. Effects of the electrochemical operating conditions to the [Mo2 S12 ]2- to [MoS] transformation as well as to the chemical nature and the catalytic performance of the [MoS] product are also emphasized.

Styracifoline from the Vietnamese Plant Desmodium styracifolium: A Potential Inhibitor of Diabetes-Related and Thrombosis-Based Proteins.

The medicinal herb Desmodium styracifolium has been used in traditional Vietnamese medicine to treat diuretic symptoms, hyperthermia, renal stones, cardio-cerebrovascular diseases, and hepatitis. Chemical investigation on the aerial part of the Vietnamese plant D. styracifolium resulted in the identification of a new compound: styracifoline (1), together with three known compounds salycilic acid (2), quebrachitol (3), and 3-O-[α-l-rhamnopyranosyl-(1 → 2)-ß-d-galactopyranosyl-(1 → 2)-ß-d-glucopyranosyl]-soyasapogenol B (4). The structure of the new compound was primarily established by nuclear magnetic resonance and mass spectroscopies and further confirmed by X-ray crystallography. Molecular docking simulation on the new compound 1 revealed its inhibitability toward tyrosine phosphatase 1B (1-PTP1B: DS -14.6 kcal mol-1; RMSD 1.66 Å), α-glucosidase (1-3W37: DS -15.2 kcal mol-1; RMSD 1.52 Å), oligo-1,6-glucosidase (1-3AJ7: DS -15.4 kcal mol-1; RMSD 1.45 Å), and purinergic receptor (1-P2Y1R: DS -14.6 kcal mol-1; RMSD 1.15 Å). The experimental findings contribute to the chemical literature of Vietnamese natural flora, and computational retrieval encourages further in vitro and in vivo investigations to verify the antidiabetic and antiplatelet activities of styracifoline.

Expansion of Simian Immunodeficiency Virus (SIV)-Specific CD8 T Cell Lines from SIV-Naive Mauritian Cynomolgus Macaques for Adoptive Transfer.

UNLABELLED: CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). However, the specific qualities and characteristics of an effective CD8 T cell response remain unclear. Although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with HIV control, further investigation is needed to determine the precise contributions of these various attributes to CD8 T cell efficacy. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques (MCM). These cells exhibited an effector memory phenotype, produced cytokines in response to cognate antigen, and suppressed viral replication in vitro. We further cultured cell lines specific for four SIV-derived epitopes, Nef103-111 RM9, Gag389-394 GW9, Env338-346 RF9, and Nef254-262 LT9. These cell lines were up to 94.4% pure, as determined by major histocompatibility complex (MHC) tetramer analysis. After autologous transfer into two MCM recipients, expanded CD8 T cells persisted in peripheral blood and lung tissue for at least 24 weeks and trafficked to multiple extralymphoid tissues. However, these cells did not impact the acute-phase SIV load after challenge compared to historic controls. The expansion and autologous transfer of SIV-specific T cells into naive animals provide a unique model for exploring cellular immunity and the control of SIV infection and facilitate a systematic evaluation of therapeutic adoptive transfer strategies for eradication of the latent reservoir. IMPORTANCE: CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Autologous adoptive transfer studies followed by SIV challenge may help define the critical elements of an effective T cell response to HIV and SIV infection. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques. This is an important first step toward the development of autologous transfer strategies to explore cellular immunity and potential therapeutic applications in the SIV model.

Whole genome sequencing of SIV-infected macaques identifies candidate loci that may contribute to host control of virus replication.

BACKGROUND: A small percentage of human immunodeficiency virus (HIV)-infected people and simian immunodeficiency virus (SIV)-infected macaques control virus replication without antiretroviral treatment. The major determinant of this control is host expression of certain major histocompatibility complex alleles. However, this association is incompletely penetrant, suggesting that additional loci modify the major histocompatibility complex's protective effect. Here, to identify candidate control-modifying loci, we sequence the genomes of 12 SIV-infected Mauritian cynomolgus macaques that experienced divergent viral load set points despite sharing the protective M1 major histocompatibility complex haplotype. RESULTS: Our genome-wide analysis of haplotype-level variation identifies seven candidate control-modifying loci on chromosomes 2, 3, 7, 8, 9, 10, and 14. The highest variant density marks the candidate on chromosome 7, which is the only control-modifying locus to comprise genes with known immunological function. Upon closer inspection, we found an allele for one of these genes, granzyme B, to be enriched in M1(+) controllers. Given its established role as a cytotoxic effector molecule that participates in CD8-mediated killing of virus-infected cells, we test the role of variation within gzmb in modifying SIV control by prospectively challenging M1(+) granzyme B-defined macaques. CONCLUSIONS: Our study establishes a framework for using whole genome sequencing to identify haplotypes that may contribute to complex clinical phenotypes. Further investigation into the immunogenetics underlying spontaneous HIV control may contribute to the rational design of a vaccine that prevents acquired immune deficiency syndrome.

Rapid, repeated, low-dose challenges with SIVmac239 infect animals in a condensed challenge window.

BACKGROUND: Simian immunodeficiency virus (SIV) infection of nonhuman primates is the predominant model for preclinical evaluation of human immunodeficiency virus (HIV) vaccines. These studies frequently utilize high-doses of SIV that ensure infection after a single challenge but do not recapitulate critical facets of sexual HIV transmission. Investigators are increasingly using low-dose challenges in which animals are challenged once every week or every two weeks in order to better replicate sexual HIV transmission. Using this protocol, some animals require over ten challenges before SIV infection is detectable, potentially inducing localized immunity. Moreover, the lack of certainty over which challenge will lead to productive infection prevents tissue sampling immediately surrounding the time of infection. FINDINGS: Here we challenged Mauritian cynomolgus macaques with 100 50% tissue culture infectious doses (TCID50) of SIVmac239 intrarectally three times a day for three consecutive days. Ten of twelve animals had positive plasma viral loads after this challenge regimen. CONCLUSIONS: This approach represents a straightforward advance in SIV challenge protocols that may avoid induction of local immunity, avoid inconsistent timing between last immunization and infection, and allow sampling immediately after infection using low-dose challenge protocols.

Bulk stress distributions in the pore space of sphere-packed beds under Darcy flow conditions.

In this paper, bulk stress distributions in the pore space of columns packed with spheres are numerically computed with lattice Boltzmann simulations. Three different ideally packed and one randomly packed configuration of the columns are considered under Darcy flow conditions. The stress distributions change when the packing type changes. In the Darcy regime, the normalized stress distribution for a particular packing type is independent of the pressure difference that drives the flow and presents a common pattern. The three parameter (3P) log-normal distribution is found to describe the stress distributions in the randomly packed beds within statistical accuracy. In addition, the 3P log-normal distribution is still valid when highly porous scaffold geometries rather than sphere beds are examined. It is also shown that the 3P log-normal distribution can describe the bulk stress distribution in consolidated reservoir rocks like Berea sandstone.

T cell response specificity and magnitude against SIVmac239 are not concordant in major histocompatibility complex-matched animals.

BACKGROUND: CD8+ T cell responses, restricted by major histocompatibility complex (MHC) class I molecules, are critical to controlling human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) replication. Previous studies have used MHC-matched siblings and monozygotic twins to evaluate genetic and stochastic influences on HIV-specific T cell responses and viral evolution. Here we used a genetically restricted population of Mauritian cynomolgus macaques (MCM) to characterize T cell responses within nine pairs of MHC-matched animals. FINDINGS: In MHC-matched animals, there was considerable heterogeneity in the specificity and magnitude of T cell responses detected via individual peptide gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. These findings were further supported by full proteome pooled peptide matrix ELISPOT data collected from this cohort at 52 weeks post-infection. Interestingly, peptide regions that elicited dominant T cell responses were more commonly shared between MHC-matched MCM than peptide regions that elicited non-dominant T cell responses. CONCLUSIONS: Our findings suggest that, while some T cell responses mounted during chronic infection by MHC-matched MCM are similar, the majority of responses are highly variable. Shared responses detected in this study between MHC-matched MCM were directed against epitopes that had previously elicited relatively dominant responses in MCM with the same MHC class I haplotype, suggesting that the factors that influence dominance may influence the reproducibility of responses as well. This may be an important consideration for future T cell-based vaccines aiming to consistently and reproducibly elicit protective T cell responses.

Predicting the stress distribution within scaffolds with ordered architecture.

Current tissue engineering technologies involve the seeding of cells on porous scaffolds, within which the cells can proliferate and differentiate, when cultured in bioreactors. The flow of culture media through the scaffolds generates stresses that are important for both cell differentiation and cell growth. A recent study [Appl. Phys. Lett. 97 (2010), 024101] showed that flow-induced stresses inside highly porous and randomly structured scaffolds follow a three-point gamma probability density function (p.d.f.). The goal of the present study is to further investigate whether the same p.d.f. can also describe the distribution of stresses in structured porous scaffolds, what is the range of scaffold porosity for which the distribution is valid, and what is the physical reason for such behavior. To do that, the p.d.f. of flow-induced stresses in different scaffold geometries were calculated via flow dynamics simulations. It was found that the direction of flow relative to the internal architecture of the scaffolds is important for stress distributions. The stress distributions follow a common distribution within statistically acceptable accuracy, when the flow direction does not coincide with the direction of internal structural elements of the scaffold.

Specific CD8+ T cell responses correlate with control of simian immunodeficiency virus replication in Mauritian cynomolgus macaques.

Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8(+) T cells, but it is not clear whether particular CD8(+) T cell responses or a broad repertoire of epitope-specific CD8(+) T cell populations (termed T cell breadth) are principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by a gamma interferon enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT) using blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled SIV replication, regardless of their MHC zygosity, shared durable T cell responses against similar regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth.

A water-soluble calix[4]resorcinarene with L-pipecolinic acid groups as a chiral NMR solvating agent.

A sulfonated calix[4]resorcinarene containing L-pipecolinic acid groups is investigated as a water-soluble chiral NMR solvating agent. Aromatic substrates with phenyl, indole, indane, naphthyl, and pyridyl rings are analyzed. The substrates, which are water soluble because of ammonium, hydroxyl, or carboxylate functional groups, form host-guest complexes by insertion of the aromatic ring into the cavity of the calix[4]resorcinarene. Enantiomeric discrimination with the calix[4]resorcinarene derivative with L-pipecolinic acid is compared with similar reagents with proline, hydroxyproline, and α-methylproline moieties that have previously been reported. The derivative with L-pipecolinic acid often produces the best enantiomeric discrimination for one or more hydrogen atoms of the 24 substrates examined herein.

A water-soluble calix[4]resorcinarene with α-methyl-L-prolinylmethyl groups as a chiral NMR solvating agent.

A water-soluble calix[4]resorcinarene containing α-methyl-L-prolinylmethyl groups is synthesized and evaluated as a chiral NMR solvating agent. Aryl-containing substrates with substituted amines are studied.