Glass formation and shear elasticity in dense suspensions of repulsive anisotropic particles.

Kinetic vitrification, shear elasticity, and the approach to jamming are investigated for repulsive nonspherical colloids and contrasted with their spherical analog. Particle anisotropy dramatically increases the volume fraction for kinetic arrest. The shear modulus of all systems increases roughly exponentially with volume fraction, and a universal collapse is achieved based on either the dynamic crossover or random close packing volume fraction as the key nondimensionalizing quantity. Quantitative comparisons with recent microscopic theories are performed and good agreement demonstrated.

Collective diffusion in colloid-polymer suspensions: relative role of thermodynamics and hydrodynamics.

Theories such as the mode coupling theory (MCT) have seen recent success in predicting the kinetic arrest boundaries and resultant flow properties of colloidal suspensions. A key assumption of such theories is that interparticle forces and equilibrium structure control slow dynamics and gelation, not long-time many-body hydrodynamics. Here we report measurements of short-time collective diffusivities of colloid-polymer suspensions aimed at elucidating the relative contributions of hydrodynamics and thermodynamics as a phase transition or gelation boundary is approached. The experimental system is a hard sphere octadecyl silica suspension to which nonadsorbing polystyrene is added. Two different polymer molecular weights are chosen such that they give rise to a liquid-liquid or a gel transition as the colloid volume fraction or polymer concentration is increased. The short-time diffusivities are measured for each polymer molecular weight as a function of polymer concentration and colloid volume fraction. At a fixed polymer molecular weight and concentration, the colloid volume fraction is varied from dilute to concentrated and near the phase separation boundary. It is found for all measured colloid volume fractions that the diffusivities decrease linearly with increasing strength of the polymer-mediated depletion attraction at a fixed polymer molecular weight. Comparisons are made with theoretical predictions in the dilute limit. When the effects of thermodynamics are normalized out by multiplying the measured diffusivities with the suspension structure factor, it is found that the hydrodynamic effects are essentially those of hard spheres independent of the range and strength of depletion attraction.

Yielding behavior of thermo-reversible colloidal gels.

The breakdown of structure in gelled suspensions due to the application of an external stress results in flow. Here we explore the onset of flow by investigating the onset of nonlinear behavior in the elastic moduli of a widely studied class of thermo-reversible gels over a range of volume fractions. We employ the system composed of octadecyl-coated silica particles (radius = 24 nm) suspended in decalin that displays a transition from a liquid to a gel below a volume-fraction-dependent gel temperature, Tgel. The perturbative yield stress at which the gel modulus drops to 90% of its value in the linear viscoelastic limit is found to increase monotonically with volume fraction and decreasing temperature. The recently proposed activated barrier-hopping theory of Schweizer and co-workers1,2 presents a framework to capture the impact of external forces on the mechanical properties of structurally arrested systems. By characterizing particle interactions with a Yukawa potential and employing the resultant static structure factor as input into the activated barrier-hopping theory, we make predictions for how the elastic modulus evolves with the applied stress. Comparisons of these calculations with experiments reveal that the theory does an excellent job of quantitatively capturing the perturbative yield stresses over the entire range of volume fractions and temperatures explored in the study. The match of predictions with experimental results suggests that the theory not only captures particle localization but also how this localization is modulated in the presence of an external stress.

Microstructure of equilibrium fluid clusters in colloid-polymer suspensions.

Several studies on colloidal depletion systems have reported the existence of a fluid phase consisting of clusters of particles above a critical polymer concentration that acts as a precursor regime to the gel phase at low colloid volume fractions (phi

Microstructure and rheology of thermoreversible nanoparticle gels.

Naïve mode coupling theory is applied to particles interacting with short-range Yukawa attractions. Model results for the location of the gel line and the modulus of the resulting gels are reduced to algebraic equations capturing the effects of the range and strength of attraction. This model is then applied to thermo reversible gels composed of octadecyl silica particles suspended in decalin. The application of the model to the experimental system requires linking the experimental variable controlling strength of attraction, temperature, to the model strength of attraction. With this link, the model predicts temperature and volume fraction dependencies of gelation and modulus with five parameters: particle size, particle volume fraction, overlap volume of surface hairs, and theta temperature. In comparing model predictions with experimental results, we first observe that in these thermal gels there is no evidence of clustering as has been reported in depletion gels. One consequence of this observation is that there are no additional adjustable parameters required to make quantitative comparisons between experimental results and model predictions. Our results indicate that the naïve mode coupling approach taken here in conjunction with a model linking temperature to strength of attraction provides a robust approach for making quantitative predictions of gel mechanical properties. Extension of model predictions to additional experimental systems requires linking experimental variables to the Yukawa strength and range of attraction.

Microscopic dynamics of recovery in sheared depletion gels.

We report x-ray photon correlation spectroscopy and diffusing wave spectroscopy studies of depletion gels formed from nanoscale silica colloids in solutions of nonabsorbing polymer following the cessation of shear. The two techniques provide a quantitatively coherent picture of the dynamics as ballistic or convective motion of colloidal clusters whose internal motion is arrested. While the dynamics possesses features characteristic of nonergodic soft solids, including a relaxation time that grows linearly with the time since shear, comparison with behavior of quenched supercooled liquids indicates that this evolution is not directly related to traditional aging phenomena in glasses.

Scattering for mixtures of hard spheres: comparison of total scattering intensities with model.

The angular dependence of the intensity of x-rays scattered from binary and ternary hard sphere mixtures is investigated and compared to the predictions of two scattering models. Mixture ratio and total volume fraction dependent effects are investigated for size ratios equal to 0.51 and 0.22. Comparisons of model predictions with experimental results indicate the significant impact of the role of particle size distributions in interpreting the angular dependence of the scattering at wave vectors probing density fluctuations intermediate between the sizes of the particles in the mixture.

Clustering and mechanics in dense depletion and thermal gels.

We report on the microstructure and mechanical properties (elastic modulus) of concentrated depletion and thermal gels of octadecyl-coated silica particles for different values of the strength of interaction--polymer concentration for depletion gels and temperature for thermal gels. The depletion gels are composed of dense clusters and voids, while the thermal gels are devoid of clusters. Shear breaks up clusters in depletion gels while it induces clustering in the thermal gels. In both of these gels, the microstructure recovers to the presheared state upon cessation of shear. The recovery of the elastic modulus mimics the microstructure in the sense that the elastic modulus recovers to the presheared sheared state after shearing is stopped. Calculations of the gel boundary by modeling the interactions with an effective one-component square-well model reveals that suspensions with similar ranges of attraction gel at the same volume fraction at a fixed strength of attraction. Calculations of the elastic modulus using the naïve mode coupling theory for depletion gels are in good agreement with experimental measurements provided clustering is taken into account and have the same magnitude as the elastic moduli of thermal gels with similar strengths of attraction. These calculations, in addition to the experimental observations reinforce the point that the microscopic parameter determining the elastic modulus of dense gels and its recovery is the localization length which is only a fraction of the particle diameter and not the structure on the length scale of the particle diameter and larger.

Establishing a master's degree programme in bioinformatics: challenges and opportunities.

The development of the Bioinformatics MS degree program at the University of Illinois, the challenges and opportunities associated with such a process, and the current structure of the program is described. This program has departed from earlier University practice in significant ways. Despite the existence of several interdisciplinary programs at the University, a few of which grant degrees, this is the first interdisciplinary program that grants degrees and formally recognises departmental specialisation areas. The program, which is not owned by any particular department but by the Graduate College itself, is operated in a franchise-like fashion via several departmental concentrations. With four different colleges and many more departments involved in establishing and operating the program, the logistics of the operation are of considerable complexity but result in significant interactions across the entire campus.

Elasticity and clustering in concentrated depletion gels.

X-ray scattering and rheology are employed to study the volume fraction dependence of the collective structure and elastic moduli of concentrated nanoparticle-polymer depletion gels. The nonequilibrium gel structure consists of locally densified nonfractal clusters and narrow random interfaces. The elastic moduli display a power law dependence on volume fraction with effective exponents that decrease with increasing depletion attraction strength. A microscopic theory that combines local structural information with a dynamic treatment of gelation is in good agreement with the observations.

Kinetics of crystallization in hard-sphere colloidal suspensions.

We propose a kinetic model for describing crystal nucleation kinetics in hard-sphere colloidal suspensions. The model captures the interplay between the enhanced thermodynamic driving force and the reduced particle diffusivity in determining crystal nucleation rates as the particle density is increased in hard-sphere suspensions. Model calculations of nucleation rates and crystal growth velocities agree quantitatively with experimental observations. The dependence of the critical cluster size on volume fraction that emerges differs qualitatively from predictions of classical theories allowing for an experimental validation of the mechanism of crystal nucleation in colloidal suspensions.

Cytomegalovirus appendicitis in a patient with human immunodeficiency virus infection. Case report and review of the literature.

We report a case of chronic abdominal pain with subsequent development of acute right lower quadrant tenderness in a patient infected with the human immunodeficiency virus. Ultrasonography and computed tomography revealed an enlarged appendix. On subsequent laparotomy, the patient was found to have appendicitis due to cytomegalovirus. Six additional cases of this infection were identified in a review of the literature. The course of cytomegalovirus appendicitis in these patients was prolonged and atypical compared with noncompromised patients with acute appendicitis. Because perforation may occur, surgery is advocated when this diagnosis is suspected in the patient infected with human immunodeficiency virus.

Human thymocytes express a prolactin-like messenger ribonucleic acid and synthesize bioactive prolactin-like proteins.

Recent evidence has demonstrated an important immunoregulatory role for pituitary PRL. Moreover, PRLs have been identified as products of transformed human lymphocyte cell lines and normal murine lymphocytes, and implicated as regulators of their proliferative responses. However, PRL synthesis by normal human lymphocytes has not yet been reported. Here we demonstrate that human thymocytes and peripheral blood lymphocytes (PBL) synthesize PRL in primary culture. The principal form produced by thymocytes is 24 kilodaltons (kDa), essentially the same size as pituitary PRL, while PBL produced a 27-kDa variant. Size heterogeneity was evident, with products detected ranging from 21-29 kDa in various tissue samples, a phenomenon also found to occur in human pituitary and decidual PRL. Thymocytes and PBLs also synthesized a low mol wt form (11 kDa) that was released into culture supernatants concurrently with the larger PRL. The 24- and 11-kDa forms expressed PRL-like bioactivity in the Nb2 node lymphoma bioassay, further supporting their PRL-like nature. Expression of these PRLs was regulated by mitogen stimulation in thymocytes, but was constitutively produced in PBL. Northern blot analysis of thymocyte RNA using a human PRL cDNA probe detected a single PRL-like mRNA, which was significantly larger than human pituitary PRL mRNA. This was constitutively present in unstimulated thymocytes. Taken together, these data demonstrate that normal human lymphocytes synthesize bioactive PRLs similar in size to those produced by the pituitary. The presence of a single PRL mRNA suggests that the size variation observed in these proteins is probably due to posttranslational modification, such as proteolysis and glycosylation.

Up-regulation of prolactin gene expression and feedback modulation of lymphocyte proliferation during acute allograft rejection.

BACKGROUND: Although recent evidence suggests that prolactin is important in the immune response, bidirectional communication between prolactin and the immune system has not been demonstrated previously. We examined our hypothesis that this communication exists during mouse skin allograft rejection. METHODS: Serum prolactin levels were measured by bioassay, and pituitary prolactin mRNA was examined by use of Northern blots, in BALB/c mice receiving skin allografts from C57BL mice, on days 2, 4, and 6 after grafting. The feedback effects of prolactin on splenic lymphocytes were assessed in one-way mixed lymphocyte reactions, with or without added interleukin-2 (IL-2) or IL-4. RESULTS: Prolactin mRNA was increased significantly in grafted animals compared with sham animals (2.4-fold by day 4). Serum prolactin bioactivity was also elevated on all days tested. Prolactin treatment resulted in dose-dependent modulation of the mixed lymphocyte reaction with lymphocytes from grafted animals but not from sham animals. These effects depended on the time points and the presence of IL-2 or IL-4; the maximal enhancement occurred with day-4 lymphocytes cultured with IL-4 (80%). CONCLUSIONS: This report is the first to implicate in vivo immune regulation of prolactin gene expression. Our observations indicate that bidirectional interaction exists between prolactin and the immune system and provide a rationale for altering prolactin levels to treat allograft rejection.

Identification of prolactin receptors in hepatic nuclei.

Prolactin is a trophic hormone which may act directly at the hepatocyte nucleus. In this study, specific prolactin binding sites were sought in purified rat liver nuclei. Saturable and specific, high affinity 125I-prolactin binding sites were demonstrated to be on or within the nucleus. Prolactin binding was competitively inhibited by rat and ovine prolactins but not by rat growth hormone. Using immunogold electron microscopy, we detected prolactin receptors throughout the nucleus, in association with heterochromatin. Furthermore, endogenous immunoreactive prolactin was demonstrated to be within hepatic nuclei. We conclude that rat liver nuclei possess prolactin binding sites which likely participate in hormone-directed growth processes.

A specific binding site in Nb2 node lymphoma cells mediates the effects of didemnin B, an immunosuppressive cyclic peptide.

Didemnin B (DB) is a cyclic depsipeptide with a variety of biologic effects, including potent antiviral, antitumor, and immunosuppressive activities. Although its mechanism of action has been attributed to inhibition of DNA and protein synthesis, the exact cellular site of interaction has not been previously defined. Since DB is strongly antiproliferative in Nb2 node lymphoma cells, we investigated potential DB binding sites in these cells, using [3H]-DB (2.7 mCi/mg) as the radiolabeled ligand. Time course studies with Nb2 cells showed that steady state [3H]-DB binding was attained after 4 h. Scatchard analysis with resting cells yielded a Kd of 180 nM (200 ng/ml), and 7 x 10(6) binding sites/cell. The IC50 of DB inhibition of ongoing protein and DNA synthesis in Nb2 cells, measured 24 h after prolactin (PRL) stimulation, was also in the range of 100 ng/ml. Didemnin analogs, with alterations at critical amino acid residues, inhibited the synthesis of DNA and protein and competed with [3H]-DB binding with the same rank order of potency. This implies that this binding site may mediate the inhibition of macromolecule synthesis. Subcellular fractionation of [3H]-DB labeled Nb2 cells revealed that specific binding occurred predominantly in the 100,000 g cytosolic fraction. Comparison with cyclophilin and the FK506 binding protein, both cytosolic receptors, suggests that the DB binding site may also belong to the family of immunophilins.