Perspectives on weak interactions in complex materials at different length scales.

Nanocomposite materials consist of nanometer-sized quantum objects such as atoms, molecules, voids or nanoparticles embedded in a host material. These quantum objects can be exploited as a super-structure, which can be designed to create material properties targeted for specific applications. For electromagnetism, such targeted properties include field enhancements around the bandgap of a semiconductor used for solar cells, directional decay in topological insulators, high kinetic inductance in superconducting circuits, and many more. Despite very different application areas, all of these properties are united by the common aim of exploiting collective interaction effects between quantum objects. The literature on the topic spreads over very many different disciplines and scientific communities. In this review, we present a cross-disciplinary overview of different approaches for the creation, analysis and theoretical description of nanocomposites with applications related to electromagnetic properties.

Premelting of ice adsorbed on a rock surface.

Considering ice-premelting on a quartz rock surface (i.e. silica) we calculate the Lifshitz excess pressures in a four layer system with rock-ice-water-air. Our calculations give excess pressures across (1) ice layer, (2) water layer, and (3) ice-water interface for different ice and water layer thicknesses. We analyse equilibrium conditions where the different excess pressures take zero value, stabilized in part by repulsive Lifshitz interactions. In contrast to previous investigations which considered varying thickness of only one layer (ice or water), here we present theory allowing for simultaneous variation of both layer thicknesses. For a given total thickness of ice and water, this allows multiple alternative equilibrium solutions. Consequently the final state of a system will depend on initial conditions and may explain variation in experimental measurements of the thicknesses of water and ice layers.

Trapping of Gas Bubbles in Water at a Finite Distance below a Water-Solid Interface.

Gas bubbles in a water-filled cavity move upward because of buoyancy. Near the roof, additional forces come into play, such as Lifshitz, double layer, and hydrodynamic forces. Below uncharged metallic surfaces, repulsive Lifshitz forces combined with buoyancy forces provide a way to trap micrometer-sized bubbles. We demonstrate how bubbles of this size can be stably trapped at experimentally accessible distances, the distances being tunable with the surface material. By contrast, large bubbles (≥100 µm) are usually pushed toward the roof by buoyancy forces and adhere to the surface. Gas bubbles with radii ranging from 1 to 10 µm can be trapped at equilibrium distances from 190 to 35 nm. As a model for rock, sand grains, and biosurfaces, we consider dielectric materials such as silica and polystyrene, whereas aluminium, gold, and silver are the examples of metal surfaces. Finally, we demonstrate that the presence of surface charges further strengthens the trapping by inducing ion adsorption forces.

Why direct or reversed Hofmeister series? Interplay of hydration, non-electrostatic potentials, and ion size.

A modified Poisson-Boltzmann analysis is made of the double layer interaction between two silica surfaces and two alumina surfaces in chloride electrolyte. The analysis incorporates nonelectrostatic ion-surface dispersion interactions based on ab initio ionic excess polarizabilities with finite ion sizes. A hydration model for the tightly held hydration shell of kosmotropic ions is introduced. A direct Hofmeister series (K > Na > Li) is found at the silica surface while the reversed series (Li > Na > K) is found at alumina, bringing theory in line with experiment for the first time. Calculations with unhydrated ions also suggest that surface-induced dehydration may be occurring at the alumina surface.

Anion-specific partitioning in two-phase finite volume systems: possible implications for mechanisms of ion pumps.

In two-phase finite volume systems of electroneutral phospholipids, the electrolyte concentration is different in the two phases. The partitioning is highly anion-specific, a phenomenon not accounted for by classical electrolyte theories. It is explained if ionic dispersion forces that lead to specific ion binding are taken into account. The mechanism provides a contribution to active ion pumps not previously considered.

Status of electronic reporting of notifiable conditions in the United States and Europe.

OBJECTIVE: To improve the computer connectivity and network strategies to connect U.S. county health departments (CHDs), state health departments (SHDs), and the Centers for Disease Control (CDC) for reporting notifiable conditions. METHODS: HSPNET-L mailing list discussions and individual Internet communications were used to compare selected features of notifiable conditions networking in the United States, France, and the United Kingdom. RESULTS: In the US, the CHD is the agency that first responds to an infectious disease outbreak on receiving notifications from physicians. Prompt recognition by the SHD that a widespread outbreak has occurred depends on the way in which county data are received, the "age" of the data, and the time taken to analyze them. Similarly, the recognition of the national scale of the outbreak depends on the promptness with which SHDs report to the CDC and the age of the data. An analysis of the French Communicable Disease Network suggests that an expansion of electronic links between US CHDs and SHDs will improve timeliness. Electronic data exchange allows CHDs to set up a local database and reduces transcription errors, mailing costs, and telephone costs. CONCLUSION: A fuller use of e-mail or other electronic communication by US CHDs will allow them to use a local database as a tool for managing local disease outbreaks more effectively and independently. Federal and state agency access to the CHD databases will enable early reporting of epidemic outbreaks. Periodic posting of public health information on Internet servers is recommended for immediate access to the public health data by Internet users worldwide.

Binding of some metastatic tumor cell lines to fibrous elastin and elastin peptides.

Recent suggestions that tumor-cell targeting of elastin-rich tissues (e.g., lung) correlates with the presence of surface elastin receptors have been investigated. Receptors for insoluble (fibrous) elastin and for soluble elastin peptides have been implemented in these correlations. A rapid assay for binding of insoluble elastin has been devised. Two of the cell lines tested (M27 and MAT-LyLu), which metastasize to the lung, strongly bound fibrous elastin whereas a third (B16-F10) did not. None of 4 metastatic cell lines that do not target the lung (A549, 3LL, TA3, TA3-iso2) bound fibrous elastin. The ability of cell lines to interact with soluble elastin was tested by cell attachment to high-molecular-weight soluble elastin peptides adsorbed on a plastic surface. Three of 7 tested cell lines, B16-F10, M27 and TA3, attached to a soluble elastin coating. In contrast to the rapid binding of insoluble elastin particles, the cell interaction with immobilized soluble elastin peptides was delayed, suggesting that induction of receptors for soluble elastin and/or modification of the elastin coat was occurring. Thus, all 3 tested cell lines where metastases target the lung, namely, MAT-LyLu, B16-F10 and M-27, show soluble- or insoluble-elastin interactions, whereas, of 4 cell lines not targeting lungs, only one, TA3, reacts with soluble elastin.

Tumor cell interactions with stromal elastin and type I collagen: the consequences of specific adhesion and proteolysis.

Elastin and collagen are abundant fibrous molecules in the stroma. Tumor cells invading the stroma are in contact with fibers of both types much of the time. Both may serve as footholds for the traction required for movement. Elastin has an additional role. Elastin peptides are known to stimulate receptor signaling and chemotaxis, which could explain the morphometric changes (membrane and organelle polarization and cell volume shrinkage) that we have reported for certain tumor cell lines invading elastic lamina. Elastin and its peptides emerge as possible invasion enhancers for some tumor cells. In ongoing work we are screening human tumors that contact elastin (e.g., breast carcinomas) to see if the presence of elastin receptors correlates with early dissemination of metastatic tumor cells.

Organelle rearrangement and cell volume changes during squeezing invasion of peritoneal elastic lamina by targeted murine breast carcinoma cells.

Murine breast cancer cell lines were developed to selectively invade the peritoneum while they proliferated in ascites form in the abdominal cavity. In a dominant form of invasion, tumor cells showed special affinity for elastin fibers and squeezed through narrow gaps in the elastic fiber meshwork of the stroma. Even in fixed tissue, such cells could be recognized as being in the process of invasive migration because of their dumbbell shape. This appearance was similar to that of diapedetic blood cells traversing bone marrow sinus endothelium. Three-dimensional STERECON graphics reconstruction from serial thick sections of 44 such cells was carried out. The reconstructions showed that, in mid-penetration, the cells spread extensively over the exterior surface of the elastic fiber meshwork. The cell surface contact of these forward projections was mainly with the elastic fiber outer coat of microfibrils, but small areas of the cell surface also fused directly to inner-core elastin. The morphological rearrangement of the cytoskeleton was minimal in both types of attachment areas. The location of these forward facing attachments is consistent with mechanisms for pulling the invasive cell through the gap. Lamellopodia formation and clustering of cytoplasmic organelles occurred more commonly at the forward-facing part of the cell. Morphometry of the reconstructions showed that a contraction of the whole cell occurred during the squeezing/migration process suggestive of an additional pushing process. However, our invasive cell lines showed marked differences in the degree of cell shrinkage. The process of adhesion and squeezing of tumor cells through elastin meshworks in vivo is clearly a complex phenomenon. Changes in cell surface activity appear to play a significant role in establishing the necessary 'foothold' component of invasion and, possibly, in the generation of tractive force as well.

The relative merits of direct morphometry of reconstructions of whole cells, and statistical morphometry by stereology of random sections of cells.

Stereology, or the derivation of quantitative, three-dimensional (3-D) data about cells by statistical analysis of the structures of random sections, is widely used in cytology and pathology. However, there are situations where this approach is inadequate, and only an analysis of a homogeneous population of whole cells will give the required results. This involved 3-D reconstruction from physical or optical sections, or tomography or photogrammetry of whole-cell mounts. Use of stereo views of individual sections or projections adds considerably to the information available for both contouring and reconstruction. Recent image-processing advances in clinical radiography have shown, for the first time, that rapid, high-resolution digitization and contrast enhancement enable nearly all structural details to be routinely extracted from the micrographs and adequately portrayed. Three-D whole-cell reconstructions provide the digital data for many kinds of morphometric measurements on both whole cells and their individual organelles and membranes. Rapid fixation or freezing allows improved quantitative structure/function correlations of organelles with disturbances in cell metabolism or gene expression.

Targeting of peritoneum by the small numbers of isogeneic and allogeneic ascites carcinoma cells that infiltrate or attach to peritoneum during ascites growth.

In the course of development of an in vivo invasion model, sublines of a series of allogenic and isogeneic carcinoma cell lines have been selected that show enhanced invasion of the peritoneum. It was found that, during the proliferation of tumor cell lines in ascitic form in the abdominal cavity, small numbers of cells infiltrated or firmly adhered to the peritoneum in at least 8/12 of the tumor-host combinations tried. After thorough washing of the peritoneum it was disaggregated by an enzyme mixture, and the resulting mixture of normal and tumor cells was inoculated intraperitoneally. Peritoneal isolations were made serially for 3 to 12 times. In 6 of 8 cases where the isolation produced a stable ascites, the cells showed enhanced peritoneal invasion compared with the parent cell line. The invasion of some of the cell lines was tested in another invasion model consisting of cultured mouse buccal mucosa (9/10 cell lines invaded the explant). In 3/3 cell lines showing enhanced peritoneum invasion in vivo, there was no enhanced invasion of the buccal mucosa. The enhanced peritoneum invasion appears to be tissue specific rather than a general increase in invasion potential. Pairs of high- and low-invasive cell lines were obtained that should be useful for screening for invasion modulating agents using the mouse ascites/peritoneum in vivo model. It is suggested that the method might be generalized to produce various tumor cell lines that target for the normal tissues that are adjacent to proliferating solid or circulating tumors.

Telecommunication discussion groups for health services and medical research.

International university and research institute telecommunication links provide free or low-cost access to several computer networks (commercial and non-commercial). Previously used by science researchers, such networks are now used in clinical and social medicine. University affiliation, a personal computer, and a modern and software are needed. A host-computer, at a local computing centre, operates server software that automatically distributes information to subscribers. The server stores all messages in a monthly logbook that can be edited to produce an electronic magazine. The magazine can also be accessed by non-subscribers. The software gives convenient, fast, single-key processing of messages and files and also allows on-line conferences. Discussion groups on several medical specialties and data bases for AIDS and other communicable diseases are already operating.

High-voltage electron microscopy and three-dimensional graphic study of R and T cells in head and neck carcinomas.

Individual head and neck carcinomas show extreme regional cellular differentiation. Some cells are rich in keratin filaments (T cells) and some have little keratin and a high density of free ribosomes (R or RT cells). We attempted to isolate these two cell types in order to test their relative invasiveness in an in vitro model. The high frequency of mitosis of hyperkeratinized cells showed that there was no constraint on the motility of cell division. High-voltage electron microscopy of serial thick sections and three-dimensional graphic reconstruction demonstrated that keratin cytoskeleton filaments were cross-linked into short, thick bundles. However, the keratin cytoskeleton was absent from some portions of the cytoplasm. In normal differentiated keratinized cells, a more uniform spanning of the whole cell by thin keratin intermediate-filament bundles was evident. The cytoplasm may be more mobile in the keratinized tumor cells. Even heavily keratinized T cells, like the less keratinized cell types, may have invasive motility.

Shape, size, and distribution of cell structures by 3-D graphics reconstruction and stereology. I. The regulatory volume decrease of astroglial cells.

This report discusses fundamental limitations in attempting to derive cell size, shape, or distribution from the two-dimensional images provided by conventional electron microscopy. Morphometric or stereologic measurement of random thin sections is a convenient way to obtain some information of this type. However, it cannot provide complete, objective information about real size, shape, or connectivity of cells containing irregular or unevenly distributed structures or nonuniform populations of cells. Anisotropic structures require analysis of a complete set of serial sections. The analysis may utilize either stereo, mono, or tilted optical slices, and subsequent integration of this information into a single 3-D computer data set. In this study, we analyze stereo pairs of high-voltage electron micrographs of serial thick sections (0.5 micron) and critical-point-dried whole-cell mounts of rat brain astroglial cell cultures. The Z-axis resolution is increased by digitizing contours at discrete levels within each stereo view. This is accomplished with a new type of stereoscopic contouring device. We calculated area and volume changes accompanying hypo-osmolar swelling and spontaneous reversal of the swelling. (Regulatory Volume Decrease-RVD). An understanding of the mechanism of swelling of astroglial cells is important for improving the treatment of brain injury. The total cell-volume results are comparable with results previously obtained using nonmetabolized, radioactively tagged compounds that diffuse into various cell compartments. Our serial-section and whole-cell data also provide new information about the relative swelling of nucleus, cytoplasm, and individual organelles such as mitochondria. The basic biological problem being approached is whether homeostasis of cell function is accompanied by surface area and volume regulation of enzyme-rich membranes and organelles. Conversely, it is proposed to explore the possibility that abnormal organelle areas and volumes are indicators of perturbations of cell division, metabolism, or gene expression.

Electron microscopy, electron diffraction, and element analysis of wet biological specimens.

Temperature controlled differentially pumped environmental chambers now allow more routine examination of wet specimens in the electron microscope. A sensitive test of their efficiency is the ability to provide high resolution electron diffraction patterns from wet, unfixed protein microcrystals. Fortunately, wet specimens can be prepared with only a few tens of nanometers thickness of remaining water, so extraneous electron scattering by liquid water can be kept to a minimum. It still remains to be determined whether microprobe analysis (X-ray or electron energy-loss spectroscopy) using wet specimens gives better element localization in cells than the current freezing methods. More extensive comparisons are also required of the ultrastructural preservation and visibility of macromolecules immersed in a thin layer of water vs immersion in a thin layer of amorphous ice. However, the recent introduction of commercial forms of the necessary equipment now make these comparisons more feasible.

Resolution as a function of accelerating voltage in electron microscopy of semithick biological specimens.

In the past, biological sections ranging in thickness from 0.10- to 0.50-micron have usually been examined with high-voltage (greater than 500 kV) electron microscopes (HVEM). Now investigators are increasingly using intermediate voltage (200-500 kV) electron microscopes (IVEM), which are more readily available and demand less maintenance. In a study of "typical" plastic-embedded, stained sections of mouse liver ranging from 0.10 to 1.0 micron thick, we determined the resolution obtainable at 100, 200, and 1000 kV. At all three accelerating voltages the resolution (2.7 nm) for 0.10-micron sections was limited only by the sections stain granularity. For 0.25-micron thickness the resolutions were 5.8, 3.1, and 3.1 nm at 100, 200, and 1000 kV, respectively. The maximum usable thickness at 200 kV with resolution sufficient to resolve membranes clearly was between 0.75 and 1.0 micron, depending on the magnification. Resolution at 100 kV was adequate for screening sections up to 1.0-micron thick for preparation defects prior to examination with an IVEM or HVEM.