Search

Over the last several years, the U.S. capital markets have witnessed a palpable rise in the number and influence of so-called “activist investors”, meaning large, institutional investment funds employing an investment strategy of acquiring relatively large blocs of stock in publicly traded companies and wielding their legal rights as stockholders to effect some sort of policy change within the company but without attempting to acquire control. This fact concomitantly has engendered a heated debate as to whether activists’ rising influence is normatively “good” or “bad”. One thing in particular that makes this debate so contentious is activism’s resistance to easy characterization: on the one hand, stockholder activists primarily wield only the legal rights that the corporation law (and specifically the Delaware General Corporation Law (the “DGCL”), as Delaware is the State of incorporation for the majority of the U.S.’s publicly traded corporations) confers on investors to protect their investments, but, on the other hand, activist campaigns may cause collateral damage to the companies involved, implicating boards of directors’ fiduciary duties to protect the enterprise against threats to the corporate bastion. Simply put, does stockholder activism merely represent “dissent within the forum” that Delaware law is designed to safeguard, or are activists the proverbial “barbarians at the gate” that Delaware law entrusts corporate directors to repel? Whatever the answer to these and related questions, the extent to which stockholder activism primarily implicates the legal rights and duties of investors and directors vis-a-vis each other means that the DGCL and the Delaware courts necessarily serve an important intermediary role. And yet, the public policy of the State of Delaware as to matters of corporate internal affairs is to enable private ordering and eschew “one size fits all” approaches to the innumerable ways in which market participants may choose to deploy their capital as efficiently as possible in their respective circumstances. In other words, the intent of Delaware corporation law — and the function of Delaware courts in interpreting and enforcing that law — is not to take a position on the outcome of the debate surrounding stockholder activism, but to safeguard the debate itself. In this chapter, we highlight through practical examples the Delaware courts’ core competency in deciding these sometimes vexing questions in context with the tools available.

The ultrastructural and three-dimensional arrangement of elastic reticulum and collagen in mouse parietal peritoneum is described for the first time. As seen by high-voltage electron microscope stereoscopy of thick sections, the EL forms a three-dimensional network without free ends. The central part of the EL fibre is not amorphous but contains irregular 500-100 nm fibrils along its length. Large bundles of banded collagen (also without free ends) course in and out of the elastic reticulum. The production of these two interlacing networks implies the presence of a histo-architectural sensing and orientation system for the projected cytoplasmic processes of stromal fibroblasts and also bidirectional chain assembly for both collagen and elastin. Bilaterial assembly patterns have been described for collagen but not for elastin. The periodicity of the banded collagen varies in different regions of the fibre. A similar banding periodicity variation has been reported for Type I tendon collagen in association with local tension variations and curvature of the fibres. An unbanded type of collagen (so far not characterized as to type) lies between the elastic reticulum and the mesothelial cell basal lamina. It is speculated that the banded collagen may play a role in control of transudate across peritoneum and its disorganization in inflammation may relate to affect ascites production.

Structural changes of carcinoma cells and fibroblasts migrating through small spaces in the elastic-collagen reticulum of mouse peritoneum have been studied by high-voltage electron microscopy of serial thick sections and by computer graphics reconstruction of cell profiles. The change of shape profile of an individual cell, between serial sections is large and the distribution of organelles is very non-uniform and changes markedly between sections. Conclusions about adhesion, intercell contact, cell shape and polarization of cytoplasmic organelles could only be reached by assessing a complete set of serial sections. Our preliminary results suggest that interesting structural changes occur in both carcinoma cells and fibroblasts when migrating through this tissue.

SUMMARY Levels of impairment of electron-microscopic images of biological specimens stemming from radiation damage are assessed in a rapid visual procedure that involves taking a pair of low-fluence micrographs of a specimen area before and after a fraction of the picture area has been more seriously damaged by applying a measured electron fluence. The pair of micrographs is treated as a mock-stereo pair and is given contrasting colours. Lateral displacements of specimen details appear as false relief and changes in electron lucency as false colour.

SUMMARY A user evaluation has been made by electron microscopists of an X-ray film for routine electron microscopy. The recent improvements in mammographic X-ray films, with the attempt to reduce the patient dose required to produce a high-resolution mammogram, have resulted in some useful films for medium- and high-voltage electron microscopy. They can yield essential cytological information with a reduction of the electron fluence (exposure) applied to the specimen of more than an order of magnitude compared with conventional electron-microscope films. Their use is indicated in situations where beam damage is severe.

This review attempts a physical definition of the technical problems and achievements in applying the high-voltage electron microscope (HVEM) to biological and medical research. It is hoped that the review will summarize for biologists, funding agencies, and institutions the achievements of the HVEM, its future prospects, and the main problem areas that still need to be explored.

The construction of a microminiature axial magnetic field probe, and its associated instrumentation, is described. With an active area measuring approximately 100×100 μ, and an over‐all cross‐sectional dimension of 1.2 mm diam, the probe is sufficiently small to be maneuvered about within the polepiece of a conventional electron microscope objective lens. The axial component of the magnetic field can be measured on, as well as off, the axis of the polepiece to a higher spatial resolution than can be achieved with a commercial axial probe.

The relation between the degree of use and the available assistance has been surveyed for 18 high-voltage (⩾1 MV terminal voltage) electron microscope operations. The survey elicited information about the available time, the budget, the technical staff, and the numbers of users, projects, and micrographs produced. Large differences in activity were found among the installations. High output seems to depend on the extent of local and regional interest and also on the expertise and numbers of the technical staff. Only five of the installations regularly operate more than one shift a day. Restriction to one shift is usually due either to lack of user demand or to lack of funding for additional technicians. Except at three dedicated biological HVEMs in the United States, biologists have made much less use of the HVEM than have materials scientists. The reasons have not been established. Some additional suggestions (based upon information not derived from the survey) are offered for improved management of HVEM operations.

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.

Dark cells (DC) could be reproducibly demonstrated by differential toluidine-blue staining and electron microscopy (EM) of NYLR/Nya 16- to 19-day embryo and new born skin and phorbol ester-treated or untreated young adult skin, High-voltage electron microscopy on the same or adjacent sections showed that toluidine-blue staining picks out some but not all the DC seen by EM. The ultrastructure of DC was similar in all the above situations, except that phorbol ester-induced DC showed a less contracted nucleus. No support was obtained for DC as stem cells either for basal-cell hyperplasia or for development of hair follicle or gland outgrowths. Most of the severely contracted DC (Types 3 and 4) were assumed to have undergone an apoptotic type of cell death. Two phenomena that may have caused the contraction and apoptosis were observed. Formation of a "contraction vacuole" adjacent to the DC probably led to a loss of intercellular communication. An apparent necrosis of dermal capillaries in areas of abundant follicle downgrowth probably produced local anoxia. Further characterization of DC requires a search for cytochemical or immunologic markers, analysis of intracellular calcium and other elements, and the cloning of sub populations of basal cells that can be selectively induced to form DC.

Projecting subunits were seen on the cristae of all 11 types of mitochondria examined by electron microscopy. These consisted of a stem, 30 to 35 A wide and 45 to 50 A long, and a round head 75 to 80 A in diameter. The outer membranes of rat liver mitochondria showed regular arrays of hollow cylindrical subunits 60 A by 60 A.

We now have the tools to quantitate and correctly interpret the size, shape, and distribution of organelles in cells. It appears likely that the results will require some changes in some basic assumptions of ultrastructural cytology. This should also result in some new biochemical hypotheses about control of cell metabolism.

In an experiment to evaluate the merit of isopycnic centrifugation as a method of separating cell types in human head and neck squamous cell carcinomas, cells have been isolated from four specimens of these tumors and subjected to isopycnic centrifugation in continuous Percoll gradients. Cell types were identified by electron microscopy. The R- (ribosome-rich), T- (tonofilament-rich), and RT- (intermediate) cell types yielded broad bands overlapping extensively with one another, and partially with the bands of leukocytes. The pattern differed for each tumor studied, so that universal density levels separating given cell types could not be found. Isopycnic centrifugation proves less suitable in analyzing cells dispersed from solid tumors than for cells in suspended culture, blood, effusions, etc., probably because of heterogeneous growth conditions of cells in solid tumors.

A unique design for a polarimetric fiber -optic pressure sensor, its performance, and some preliminary experimental results are presented. Methods for reducing temperature sensitivity, which often limits the sensor's resolution, are alsodescribed.1. INTRODUCTIONDetection capabilities of pressure sensors are often limitedby their sensitivity to temperature changes. Fiber -optic (FO)sensors are very sensitive to temperature changes and makeexcellent temperature sensorsl. One challenge to developing sensitive FO pressure sensors (FOPS's) is to reduce theirtemperature sensitivity. The Mach -Zehnder FOPS in [2] minimizes interferometer noise by utilizing a nonlineargeometry for the optical fiber (OF) and phase sensitive detection. A FO sensor that utilizes a two core OF to measurepressure and temperature simultaneously is described in [3]. The FOPS described in [4] detects pressure by opticallymeasuring the resonant frequency of a small mechanically resonant structure. Operating this sensor at high frequenciesand using materials with thermally stable properties minimizes

Morphological changes of rat-liver mitochondria brought about by swelling and ATP-induced contraction were studied by electron microscopy. The course of swelling is proposed to be as follows: Entering of water (and solutes) causes breakage of the outer membrane and formation of protrusion of the inner membrane. The distention of the inner membrane is accompanied by loss of density of the matrix and by disapperance and change of shape of the cristae, probably due to their unfolding and evagination. Both membranes seem to possess a limited ability to stretch. Addition of ATP to mitochondria swollen in the presence of either orthophosphate, oleate and thyroxine gave rise to structures different from mitochondria before the onset of swelling. Restoration of the mitochondrial morphology was not observed. It is thought that the processes initiated by ATP are not a simple reversal of swelling.

It is now possible to work with wet materials by using environmental chambers. Biologists would like to evaluate the advantages of this development. The unknowns are: (a) the difficulty of constructing the equipment and it's commercial availability, (b) the problems in preparing wet specimens and viewing them, (c) the resolution and contrast available (d) the difficulties peculiar to wet specimens and (e) the advantages of wet over frozen specimens. Finally, there remains the question - can living cells be examined? This talk will attempt to answer these questions. Routine wet electron microscopy has followed the introduction of differentially pumped chambers in place of film sealed chambers. Electron diffraction patterns of wet protein crystals (Fig. 1) provide a sensitive test of the performance of hydration chambers. If the vapor pressure drops more than 10% below saturation the pattern disappears due to the disorganization of drying.