A recent article by Matthias Rief, Filipp Oesterhelt. Berthold Heymann, and Hermann Gaub concluded with this sentence: "Single molecule force spectroscopy by AFM has proven to be a powerful addition to the nanoscopic piconewton toolbox," Everything about that conclusion is tiny. Clearly, the atomic force microscope (AFM) has given us a tool to examine structure at or near the atomic level. Earlier work from Gaub's laboratory, reviewed in this column, demonstrated that the AFM could directly measure the binding force between single molecules of biotin and avidin. This established that the AFM could be used as a tool to measure forces, not just observe structure. Their most recent experiments has added to this tiny toolbox.

Ever since membranes could be resolved within cells, the pattern of intracellular membrane trafficking has been under investigation. Images made with the transmission electron microscope revealed numerous small vesicles that appeared to be shuttling between the endoplasmic rettculum (ER) and the Golgi complex. However, these static images offered no information as to the direction trie vesicles were moving and were quite inconclusive. Nevertheless, evidence built over time to suggest that unrefined proteins were moved in small vesicles from one intracellular compartment to another. Recently, a study by John Presley, Nelson Cole, Trina Schroer, Koret Hirschberg, Kristen Zaal, and Jennifer Lippincott- Schwartz with the light microscope has challenged this view. They not only presented convincing morphologic data in their published article, but they also posted some Quicktime movies on a Web site (http://dir.nichd.nih.gov/CBMB/pb1labob.html) that are even more convincing.

It has long been appreciated that communication between the nucleus and the cytoplasm of a cell occurs through the nuclear pores. Regulation of this communication has remained a mystery. A breakthrough in our understanding of this regulation was recently presented by Carmen Perez- Terzic, Jason Pyle, Marisa Jaconi, Lisa Stehnc-Bittel, and David Clapham of Mayo Clinic. Using field emission scanning electron microscopy (FESEM), transmission electron microscopy, and atomic force microscopy (AFM), they demonstrated the presence of a small plug within the nuclear pore that was present under certain physiologic circumstances. This “plug“ may regulate the movement of molecules through the pore.

The tungsten mineral wolframite was known in the tin mines of the Saxony-Bohemia region long before the element itself was discovered. The origin of the word is assumed to be derived from the German words "wolf, meaning beast of prey, and "rham", meaning froth. "It eats up tin as a wolf eats up sheep". The writers of the period before 1781 had vague ideas as to the composition of the mineral that they had named. Tin miners called the mineral "mock-lead", an ore containing iron, arsenic, tin and a nonmetallic earth, or glassy earth containing iron and tin.

As reviewed in this column on previous occasions, the atomic force microscope (AFM) is steadily making headway as an instrument that can make important contributions to biologic observations. Although the AFM is capable of operating in an aqueous environment, relatively little use has been made of this property to examine cellular structures under conditions that resemble those in vivo. A breakthrough in this regard was recently made by Stefan Schneider, Kumudesh Sritharan, John Geibel, Hans Oberleithner, and Bhanu Jena. of Yale University and the University of Würzburg.

There are many reasons for NOT using grease-base polishes for cleaning parts to be inserted into the interior of high vacuum systems, as is so commonly done in electron microscopy laboratories. This matter is discussed in some detail in my book Vacuum Methods in Electron Microscopy. (Portland Press, Ashgate Publishers, 800-535-9544), pp. 69-74.

Basically, one principal reason for cleaning most parts in the first place is to remove hydrocarbon materials from their surfaces, and so it makes no sense at all to use a greasy material to do the job.This is the equivalent of taking a bath in a mud puddle. Then, it becomes necessary to use ‘toxic’ organic solvents to remove the grease-base compounds, which in turn generates expensive and annoying procedures for the use and disposal of the solvents. In addition, the grease and abrasive materials are likely to get embedded in cracks and crevices of the parts on which they are used, and since they often are not readily soluble they may not be completely removed, whereupon they will subsequently act as a persistent source of contamination inside the vacuum system.

Spherical and chromatic aberrations have been the bane of optical lenses ever since they were first ground from a piece of glass. As light travels through a convex (converging) lens, the rays at the center of the optical axis are refracted (bent) less than the peripheral rays, so that the central rays are focused behind the peripheral rays. This is the essence of spherical aberration. Light of differing wavelengths (colors) interact differently with the lens so that longer wavelengths (red) are focused behind shorter wavelengths (blue). This is chromatic aberration. In the early days of light microscopy, these two inherent flaws seriously limited the quality of images.

Atomic force microscopy (AFM) has proven to be very useful to material scientists and physicists. Biologists are only beginning to utilize the potential of this methodology. In a recent article, Tatsuo Ushiki, Jiro Hitomi, Shigeaki Ogura, Takeshi Umemoto, and Masatsugu Shigeno reviewed the applications of AFM to biologic studies.

They began by reviewing the basic principles of AFM, emphasizing the value of the non-contact mode for visualizing the relatively “soft” surface of biologic specimens. They presented some examples of biologic images: DNA, chromosomes, and collagen fibrils. The specimens examined with the AFM did not need to be coated, theoretically offering a view with a smaller potential for artifacts. AFM images have the advantage of containing quantitative information about the sample height.

Recently, I had a delightfully pleasant surprise. I was attending a Human Embryology Conference in Washington, D.C., held at the National Museum of Health and Medicine, a Division of the Armed Forces Institute of Pathology. I've heard of the AFIP many times, but I had never been there, didn't even know where it was located. AFIP is located on the campus of Walter Reed Army Medical Center, which is bordered by Georgia Avenue. If you're driving, it's near the Maryland state line. If you're taking the Metro, get off at the Silver Springs stop and take a taxi.

Atomic Force Microscopes (AFM) can measure the force between a surface and the tip of a cantilever as a junction of separation with great precision. For example, van der Waals type forces and electrostatic repulsive forces can easily be measured in aqueous solutions using an AFM. The complex, pyramidal shape of the typical AFM cantilever is, however, not well suited for quantitative measurements. It is thus desirable to attach particles of known geometry (usually spheres) to the tip of a cantilever.

The chain of events that led to the invention of the electron microscope is an interesting story by itself. This chain has a common theme, namely electrons, and its first link is a natural phenomenon: lightning.

A flash of lightning generates a stream of electrons with a potential energy difference of 100 to 200 megavolts between clouds acting as electrodes, Benjamin Franklin envisioned this as a source of energy and tried to snatch electricity from the skies, but this proved to be too dangerous.

At the beginning of the century, lightning was a problem for electrical utilities because it produced surges that disrupted the steady flow of electricity along high tension lines. For this reason, in 1929 a high tension laboratory was founded in Germany with the sole aim of finding a way to test electrical transmission lines so as to make them capable of withstanding the lightning surges.

A question that often comes up when archiving Macintosh image files to CD-ROMs so that they can be read by either DOS or Mac computers is "What happens to the Mac resource fork of the image file?"

PC Exchange, which is built into System 7.x, creates a hidden resource fork directory on PC disks that have Mac files on them, along with additional Finder info files which contain information about file type and creator, icons, position of icons in windows, etc, Although these additional files are marked as hidden, they can be read and presumably copied by Windows '95 directly.

When an electron passes through matter, the energy of the electron is transferred to the material in the form of ionizations and excitations. Almost all of this transfer is the result of the Coulomb interaction of the beam electrons with the electrons in the specimen; that is, scattering of beam electrons by nuclei is not an important energy-transfer process.

On average, about 30 eV is transferred for each ion pair (the electron and the parent atom) produced, and most of the energy transferred goes into primary or secondary ionizations. In a typical energy-loss process, an electron can be removed from an inner shell (it can leave the atom with a velocity comparable to that of the incident electron).