From nanoparticles to nanocrystalline bulk: percolation effects in field assisted sintering of silicon nanoparticles.

Nanocrystalline bulk materials are desirable for many applications as they combine mechanical strength and specific electronic transport properties. Our bottom-up approach starts with tailored nanoparticles. Compaction and thermal treatment are crucial, but usually the final stage sintering is accompanied by rapid grain growth which spoils nanocrystallinity. For electrically conducting nanoparticles, field activated sintering techniques overcome this problem. Small grain sizes have been maintained in spite of consolidation. Nevertheless, the underlying principles, which are of high practical importance, have not been fully elucidated yet. In this combined experimental and theoretical work, we show how the developing microstructure during sintering correlates with the percolation paths of the current through the powder using highly doped silicon nanoparticles as a model system. It is possible to achieve a nanocrystalline bulk material and a homogeneous microstructure. For this, not only the generation of current paths due to compaction, but also the disintegration due to Joule heating is required. The observed density fluctuations on the micrometer scale are attributed to the heat profile of the simulated powder networks.

Changes in sperm plasma membrane lipid diffusibility after hyperactivation during in vitro capacitation in the mouse.

We have used the technique of fluorescence recovery after photobleaching to measure the diffusibility of the fluorescent lipid analogue, 1,1'-dihexadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate on the morphologically distinct regions of the plasma membranes of mouse spermatozoa, and the changes in lipid diffusibility that result from in vitro hyperactivation and capacitation with bovine serum albumin. We found that, as previously observed on ram spermatozoa, lipid analogue diffusibility is regionalized on mouse spermatozoa, being fastest on the flagellum. The bovine serum albumin induced changes in diffusibility that occur with hyperactivation are also regionalized. Specifically, if we compare serum incubated in control medium, which maintains normal motility, with those hyperactivated in capacitating medium, we observe with hyperactivation an increase in lipid analogue diffusion rate in the anterior region of the head, the midpiece, and tail, and a decrease in diffusing fraction in the anterior region of the head.

Regionalization and lateral diffusion of membrane proteins in unfertilized and fertilized mouse eggs.

The unfertilized mouse egg has a round and highly villated main body and a "nipple" that is unvillated and buds off on fertilization to form the second polar body. Fluorescent markers stain the body more intensely than the nipple, which has been assumed to result from surface amplification due to microvilli. Using fluorescence recovery after photobleaching and microfluorescence photometry, we have measured the membrane protein diffusion and concentration on the main body and nipple region of unfertilized and on fertilized CD-1 mouse eggs. Two general membrane protein labels were used: rhodamine-labeled succinylated concanavalin A and trinitrobenzene sulfonate visualized with a rhodamine Fab fragment of a sheep anti-trinitrophenyl. We found that while the diffusion coefficient was the same on the nipple and main body, considerably higher recovery was observed on the nipple for both probes. The ratio of intensity of fluorescence on the nipple to main body was significantly lower for the concanavalin A stain than for the trinitrophenyl stain, indicating that true concentration gradients exist beyond those that result from surface amplification. The effect of fertilization was not general. No effect was observed for the concanavalin A stain for either diffusion coefficient or percent recovery. For the trinitrophenyl stain, percent recovery decreased approximately twofold while diffusion coefficient increased approximately threefold.

Diffusion and regionalization in membranes of maturing ram spermatozoa.

An essential feature of the "fluid mosaic model" (Singer, S. J., and G. L. Nicolson , 1972, Science (Wash. DC)., 175:720-731) of the cell plasma membrane is the ability of membrane lipids and proteins to diffuse laterally in the plane of the membrane. Mammalian sperm are capable of overcoming free random diffusion and restricting specific membrane components, both lipid and protein, to defined regions of the sperm's surface. The patterns of these regionalizations evolve with the processes of sperm differentiation: spermatogenesis, epididymal maturation, and capacitation. We have used the technique of fluorescence recovery after photobleaching to measure the diffusion of the lipid analogue 1,1'- dihexadecyl 3,3,3',3'- tetramethylindocarbocyanine perchlorate ( C16dil ) on the different morphological regions of testicular and ejaculated ram spermatozoa. We have found: (a) that the major morphologically distinct regions (head, midpiece, and tail) of the plasma membrane of both testicular and ejaculated spermatozoa are also physically distinct as measured by C16dil diffusibility; (b) that despite regional differences in diffusibility there is exchange of this lipid analogue by lateral diffusion between the major morphological regions of the plasma membrane; and (c) that epididymal maturation results in changes in C16dil diffusibility in the different regions of the sperm plasma membrane. In particular, the plasma membranes of the anterior and posterior heads become physically distinct.

The development of regionalized lipid diffusibility in the germ cell plasma membrane during spermatogenesis in the mouse.

The lipids and proteins of sperm cells are highly regionalized in their lateral distribution. Fluorescence recovery after photobleaching studies of sperm membrane component lateral diffusibility have shown that the sperm plasma membrane is also highly regionalized in the extents and rates of diffusion of its surface components. These studies have also shown that regionalized changes in lateral diffusibility occur during the differentiative processes of epididymal maturation and capacitation. Unlike mammalian somatic cells, sperm cells exhibit large nondiffusing lipid fractions. In this paper, we will show that both regionalized lipid diffusibility and nondiffusing lipid fractions develop with the morphogenesis of cell shape during spermatogenesis in the mouse. Pachytene spermatocytes and round spermatids show diffusion rates and the nearly complete recoveries (80-90%) typical of mammalian somatic cells. In contrast, stage 10-11 condensing spermatids, testicular spermatozoa, cauda epididymal spermatozoa, as well as the anucleate structures associated with these later stages of spermatogenesis (residual bodies and the cytoplasmic droplets of condensing spermatids and testicular spermatozoa), exhibit large nondiffusing fractions. Both the diffusion rates and diffusing fractions observed on the anterior and posterior regions of the head of stage 10-11 condensing spermatids are the same as the values obtained for these regions on testicular spermatozoa. Possible mechanisms of lipid immobilization and possible physiological implications of this nondiffusing lipid are discussed.

Feedback control of the metaphase-anaphase transition in sea urchin zygotes: role of maloriented chromosomes.

To help ensure the fidelity of chromosome transmission during mitosis, sea urchin zygotes have feedback control mechanisms for the metaphase-anaphase transition that monitor the assembly of spindle microtubules and the complete absence of proper chromosome attachment to the spindle. The way in which these feedback controls work has not been known. In this study we directly test the proposal that these controls operate by maloriented chromosomes producing a diffusible inhibitor of the metaphase-anaphase transition. We show that zygotes having 50% of their chromosomes (approximately 20) unattached or monoriented initiate anaphase at the same time as the controls, a time that is well within the maximum period these zygotes will spend in mitosis. In vivo observations of the unattached maternal chromosomes indicate that they are functionally within the sphere of influence of the molecular events that cause chromosome disjunction in the spindle. Although the unattached chromosomes disjoin (anaphase onset without chromosome movement) several minutes after spindle anaphase onset, their disjunction is correlated with the time of spindle anaphase onset, not the time their nucleus breaks down. This suggests that the molecular events that trigger chromosome disjunction originate in the central spindle and propagate outward. Our results show that the mechanisms for the feedback control of the metaphase-anaphase transition in sea urchin zygotes do not involve a diffusible inhibitor produced by maloriented chromosomes. Even though the feedback controls for the metaphase-anaphase transition may detect the complete absence of properly attached chromosomes, they are insensitive to unattached or mono-oriented chromosomes as long as some chromosomes are properly attached to the spindle.

Lateral regionalization and diffusion of a maturation-dependent antigen in the ram sperm plasma membrane.

We have used a monoclonal antibody ESA 152 in fluorescence recovery after photobleaching (FPR) studies of a maturation-dependent surface antigen of ram sperm. The antibody is an immunoglobulin G secreted by a hybridoma derived from NS1 mouse myeloma cells. The ESA 152 antigen is not detectable in testicular sperm. It is localized on the surface of ejaculated sperm where it is present on all regions of the surface, but tends to be concentrated on the posterior region of the head. The ESA 152 antigen can be extracted by detergents or chloroform-methanol. The extracted antigen is sensitive to proteases and migrates with an apparent Mr approximately 30,000 in SDS-containing 10-20% polyacrylamide gradient gels. FPR measurements of ESA 152 lateral mobility in the membrane yield diffusion coefficients in the range 10(-9)-10(-8) cm2/s, values typical of lipids but observed for proteins only at the fluid dynamic limit where diffusion is controlled by lipid fluidity. Immobile fractions, typical of membrane proteins, are observed on all regions. When the antigen is stained by a fluoresceinated Fab fragment of the ESA 152 antibody, the diffusibility is highly regionalized, with particularly low, but rapid, recovery on the midpiece. Cross-linking of the antigen with the intact ESA 152 antibody induces a redistribution in which the antigen is excluded from the posterior head region. This cross-linking is accompanied by increases in ESA 152 diffusibility on both the anterior head and the midpiece.

The neurotrophin receptor, gp75, forms a complex with the receptor tyrosine kinase TrkA.

The high-affinity NGF receptor is thought to be a complex of two receptors , gp75 and the tyrosine kinase TrkA, but direct biochemical evidence for such an association had been lacking. In this report, we demonstrate the existence of such a gp75-TrkA complex by a copatching technique. Gp75 on the surface of intact cells is patched with an anti-gp75 antibody and fluorescent secondary antibody, the cells are then fixed to prevent further antibody-induced redistributions, and the distribution of TrkA is probed with and anti-TrkA antibody and fluorescent secondary antibody. We utilize a baculovirus-insect cell expression of wild-type and mutated NGF receptors. TrkA and gp75 copatch in both the absence and presence of NGF. The association is specific, since gp75 does not copatch with other tyrosine kinase receptors, including TrkB, platelet-derived growth factor receptor-beta, and Torso (Tor). To determine which domains of TrkA are required for copatching, we used a series of TrkA-Tor chimeric receptors and show that the extracellular domain of TrkA is sufficient for copatching with gp75. A chimeric receptor with TrkA transmembrane and intracellular domains show partial copatching with gp75. Deletion of the intracellular domain of gp75 decreases but does not eliminate copatching. A point mutation which inactivates the TrkA kinase has no effect on copatching, indicating that this enzymatic activity is not required for association with gp75. Hence, although interactions between the gp75 and TrkA extracellular domains are sufficient for complex formation, interactions involving other receptor domains also play a role.

Lateral diffusion in planar lipid bilayers.

Direct measurements by fluorescence correlation spectroscopy of lateral diffusion coefficients of fluorescent lipid analogs in lipid bilaryer membranes indicate self-diffusion coefficients D greater than 10(-7) square centimeters per second for various lipid systems above their reported transition temperatures. Cholesterol in egg lecithin at mole ratio of 1 : 2 reduces D by about twofold, while retained hydrocarbon solvent can increase it by two- to threefold.

Rate equations and scaling in pulsed laser deposition.

We study a simplified model for pulsed laser deposition [Hinnemann, Phys. Rev. Lett. 87, 135701 (2001)] by rate equations. We consider a set of equations where islands are assumed to be pointlike, as well as an improved one that takes the size of the islands into account. The first set of equations is solved exactly but its predictive power is restricted to a few pulses. The improved set of equations is integrated numerically, is in excellent agreement with simulations, and fully accounts for the crossover from continuous to pulsed deposition. Moreover, we analyze the scaling of the nucleation density and show numerical results indicating that a previously observed logarithmic scaling does not apply.

Shear zones in granular materials: optimization in a self-organized random potential.

We introduce a model to describe the wide shear zones observed in modified Couette cell experiments with granular material. The model is a generalization of the recently proposed approach based on a variational principle. The instantaneous shear band is identified with the surface that minimizes the dissipation in a random potential that is biased by the local velocity difference and pressure. The apparent shear zone is the ensemble average of the instantaneous shear bands. The numerical simulation of this model matches excellently with experiments and has measurable predictions.

Morphologies of three-dimensional shear bands in granular media.

We present numerical results on spontaneous symmetry breaking strain localization in axisymmetric triaxial shear tests of granular materials. We simulated shear band formation using the three-dimensional distinct element method with spherical particles. We demonstrate that the local shear intensity, the angular velocity of the grains, the coordination number, and the local void ratio are correlated and any of them can be used to identify shear bands; however, the latter two are less sensitive. The calculated shear band morphologies are in good agreement with those found experimentally. We show that boundary conditions play an important role. We discuss the formation mechanism of shear bands in the light of our observations and compare the results with experiments. At large strains, with enforced symmetry, we found strain hardening.

Influence of alcohols, temperature, and region on the mobility of lipids in neuronal membrane.

Fluorescence recovery after photobleaching was used to examine lipid diffusibility in different regions of Aplysia neurons. Differences in diffusion of 1-acyl-2-(6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4- yl)]aminohexanoyl)phosphatidylcholine (NBD-C6-PC) in the cell body, axon hillock, and axon were not apparent. Lipid diffusibility during temperature variations and exposure to alcohols was also examined by photobleaching techniques. For these studies, all measurements were made on the cell body. Alcohols were found to be selective in their effects upon the diffusibility of lipid probes. Neither ethanol nor butanol affected the diffusibility of NBD-PC. However, at the same concentrations, both of these alcohols caused a significant increase in the diffusion coefficient (D) for rhodamine-phosphatidylethanolamine (Rho-PE). The diffusion coefficient for NBD-PC in the cell body plasma membrane did not increase with warming, between 4 degrees C and 25 degrees C. The fraction of lipid probe free to diffuse (per cent recovery; %R) however, increased as temperature increased, within this range. The nonconventional relationship between temperature and D was even more pronounced for Rho-PE. As temperature increased, D became smaller for this probe, concurrent with an increase in %R. These results suggest that immobile viscous lipid is recruited into a mobile fraction as temperature increases, resulting in the maintenance of constant diffusibility. The effects of temperature on D and %R, and the selective effects of alcohols on lipid diffusibility suggest that the membrane is heterogeneously organized, on a submicroscopic scale, into domains. The implications of this organization for nerve function and responses of nervous systems to temperature and anesthetics are discussed.

Sex determination in the androdioecious plant Datisca glomerata and its dioecious sister species D. cannabina.

Datisca glomerata is an androdioecious plant species containing male and hermaphroditic individuals. Molecular markers and crossing data suggest that, in both D. glomerata and its dioecious sister species D. cannabina, sex is determined by a single nuclear locus, at which maleness is dominant. Supporting this conclusion, an amplified fragment length polymorphism (AFLP) is heterozygous in males and homozygous recessive in hermaphrodites in three populations of the androdioecious species. Additionally, hermaphrodite x male crosses produced 1:1 sex ratios, while hermaphrodite x hermaphrodite crosses produced almost entirely hermaphroditic offspring. No perfectly sex-linked marker was found in the dioecious species, but all markers associated with sex mapped to a single linkage group and were heterozygous in the male parent. There was no sex-ratio heterogeneity among crosses within D. cannabina collections, but males from one collection produced highly biased sex ratios (94% females), suggesting that there may be sex-linked meiotic drive or a cytoplasmic sex-ratio factor. Interspecific crosses produced only male and female offspring, but no hermaphrodites, suggesting that hermaphroditism is recessive to femaleness. This comparative approach suggests that the hermaphrodite form arose in a dioecious population from a recessive mutation that allowed females to produce pollen.

Piling and avalanches of magnetized particles.

We performed computer simulations based on a two-dimensional distinct element method to study granular systems of magnetized spherical particles. We measured the angle of repose and the surface roughness of particle piles, and we studied the effect of magnetization on avalanching. We report linear dependence of both angle of repose and surface roughness on the ratio f of the magnetic dipole interaction and the gravitational force (interparticle force ratio). There is a difference in avalanche formation at small and at large interparticle force ratios. The transition is at f(c) approximately 7. For f < f(c) small vertical chains follow each other at short times (granular regime), while for f > f(c) the avalanches are typically formed by one single large particle-cluster (correlated regime). The transition is not sharp. We give plausible estimates for f(c) based on stability criteria.

Diabetes: novel therapeutic developments. 21-22 September 1999, London, UK.

The treatment of diabetes represents an extremely active area of new product development. The goal is to effectively regulate glucose in a physiological manner, so as to reduce HbA1c levels and the complications of diabetes. An extremely broad range of new products for the treatment of Type I and/or Type II diabetes are in the pipeline. These include: new forms and methods of delivering insulin to increase compliance; novel pharmaceutical agents to reduce serum glucose and HbA1c levels; immunoregulatory agents which will prevent or reverse diabetic autoimmunity; glucose sensor-insulin pump feedback loops; and, transplantation of xenogeneic islets in immunoprotected microreactors.

Two-dimensional array of magnetic particles: the role of an interaction cutoff.

Based on theoretical results and simulations, in two-dimensional arrangements of a dense dipolar particle system, there are two relevant local dipole arrangements: (1) a ferromagnetic state with dipoles organized in a triangular lattice and (2) an antiferromagnetic state with dipoles organized in a square lattice. In order to accelerate simulation algorithms, we search for the possibility of cutting off the interaction potential. Simulations on a dipolar two-line system lead to the observation that the ferromagnetic state is much more sensitive to the interaction cutoff R than the corresponding antiferromagnetic state. For R approximately > 8 (measured in particle diameters) there is no substantial change in the energetical balance of the ferromagnetic and antiferromagnetic state and the ferromagnetic state slightly dominates over the antiferromagnetic state, while the situation is changed rapidly for lower interaction cutoff values, leading to the disappearance of the ferromagnetic ground state. We studied the effect of bending ferromagnetic and antiferromagnetic two-line systems and observed that the cutoff has a major impact on the energetical balance of the ferromagnetic and the antiferromagnetic state for R approximately < 4. Based on our results we argue that R approximately 5 is a reasonable choice for dipole-dipole interaction cutoff in two-dimensional dipolar hard sphere systems, if one is interested in local ordering.

Elastic behavior in contact dynamics of rigid particles.

The systematic errors due to the practical implementation of the contact dynamics method for simulation of dense granular media are examined. It is shown that, using the usual iterative solver to simulate a chain of rigid particles, effective elasticity and sound propagation with a finite velocity occur. The characteristics of these phenomena are investigated analytically and numerically in order to assess the limits of applicability of this simulation method and to compare it with soft particle molecular dynamics.

Anisotropy of electromigration-induced void and island drift.

By means of our novel self-learning kinetic Monte Carlo model (Latz et al 2012 J. Phys.: Condens. Matter 24 485005) we study the electromigration-induced drift of monolayer voids and islands on unpassivated surfaces of single crystalline Ag(111) and Ag(001) films at the atomic scale. Regarding the drift velocity, we find a non-monotonic size dependence for small voids. The drift direction is aligned with the electromigration force only along high symmetry directions, while halfway between, the angle enclosed by them is maximal. The magnitude of these directional deviations strongly depends on the system parameter, which are investigated in detail. The simulation results are in accordance with void motion observed in experiments performed on Ag(111).