bluuebunny/crossref_metadata_2025 huggingface dataset:
NOBLE GASES IN THE EARTH'S MANTLE
Authors: Farley K. A. , Neroda E.
Published: July 2002

▪ Abstract  Noble gas isotopic ratios in mantle-derived samples require variability in the time-integrated ratio of volatile to lithophile elements in the Earth. Documentation of mantle 3He/4He variability is becoming increasingly complete, but for the heavier noble gases, the picture is still partly clouded by the effects of atmospheric contamination of mantle samples. Nevertheless, clear variations in mantle Ne, Ar, and Xe isotopic ratios exist, are apparently correlated with 3He/4He, and may be the product of varying degrees of mantle degassing. However, uncertainties in noble gas geochemical behavior and several conflicting observations leave open other possibilities. Recent Ne isotopic data are particularly important because they require that the atmosphere has not been closed to exchange with space. Derivation of much of the atmosphere from a source other than degassing of the mantle is a strong possibility that complicates efforts to model the geochemical evolution of the Earth.
Vredefort, Sudbury, Chicxulub: Three of a Kind?
Authors: Grieve Richard , Therriault Ann
Published: July 2002

Vredefort, Sudbury, and Chicxulub are the largest known terrestrial impact structures. All have been cited as multi-ring basins. The available data indicate that all have some form of multiple-ring attributes, most commonly structural features. Chicxulub, however, is the only example with morphological ring features. There are also commonalities in the structural and lithological features of Vredefort and Sudbury, and it is possible to construct a generalized compilation of the character of 200–300 km diameter impact basins on Earth. It is not clear, however, that any of these structures had the original morphological characteristics of large lunar multi-ring basins. Additional data and synthesis are required to fully characterize these structures in order to realize their potential to constrain large-scale cratering processes. If this is not sufficient incentive for further studies (the environmental effects of Chicxulub aside), the Vredefort, Sudbury, and Chicxulub impact events are also the reason for the existence of world-class mineral and hydrocarbon deposits.
Evolution and Structure of the Lachlan Fold Belt (Orogen) of Eastern Australia
Authors: Foster David A. , Gray David R.
Published: July 2002

The Lachlan Fold Belt (Lachlan Orogen) of eastern Australia was part of a Paleozoic convergent plate margin that stretched around the supercontinent of Gondwana from South America to Australia. Lower Paleozoic (545–365 Ma) deep-water, quartz-rich turbidites, calcalkaline volcanic rocks, and voluminous granitic plutons dominate the Lachlan Orogen. These rocks overlie a mafic lower crust of oceanic affinity. Shortening and accretion of the Lachlan occurred through stepwise deformation and metamorphism from Late Ordovician (∼450 Ma) through early Carboniferous times, with dominant events at about 440–430 Ma and 400–380 Ma. The development and accretion of the Lachlan Orogen and other related belts within the Tasmanides added about 2.5 Mkm2 to the surface area of Gondwana. The sedimentary, magmatic, and deformational processes converted an oceanic turbidite fan system into continental crust of normal thickness. The addition of this recycled continental detritus and juvenile material to Australia represents an under-recognized continental crustal growth mechanism that has been important thoughout earth history.
Hydrogen in the Deep Earth
Authors: Williams Quentin , Hemley Russell J.
Published: July 2002

▪ Abstract  The mechanisms of exchange of hydrogen between the deep interior and surface of Earth, as well as the means of retention and possible abundance of hydrogen deep within the Earth, are examined. The uppermost several hundred kilometers of Earth's suboceanic upper mantle appear to be largely degassed, but significant primordial hydrogen could be retained within the transition zone, lower mantle, or core. Regassing of the planet occurs via subduction: Cold slabs are likely particularly efficient at transporting hydrogen to depth within the planet. Marked changes in hydrogen cycling have taken place throughout Earth's history: Evidence of hydrated ultramafic melts in the Archean and probable hydrogen retention within a Hadean magma ocean indicate that early in its history, the deep Earth was substantially wetter. The largest enigma associated with hydrogen in the deep Earth lies in the core: This region could represent the dominant reservoir of hydrogen on the planet, with up to ∼100 hydrospheres of hydrogen present as a high-pressure iron-alloy.
Pluto and Charon: Formation, Seasons, Composition
Authors: Brown Michael E.
Published: July 2002

▪ Abstract  Pluto and Charon, once thought to be a singular system in an odd orbit at the edge of the solar system, are now known as members of a vast population of icy bodies beyond Neptune. Models for the occurrence of the odd orbit and formation of these bodies in the context of the total population are reviewed. Pluto's orbital characteristics, coupled with the existence of volatiles on the surface, suggest that large-scale seasonal change should occur on the surface. Models of seasonal variability are discussed, past and current observations are examined for evidence of variability, and a straw-man model of seasonal changes is proposed. Finally, recent observations of the surface composition of Charon are discussed and compared with observations of other similarly sized icy bodies in the outer Solar System.
MECHANISMS CREATING COMMUNITY STRUCTURE ACROSS A FRESHWATER HABITAT GRADIENT
Authors: Wellborn Gary A. , Skelly David K. , Werner Earl E.
Published: July 2002

▪ Abstract  Lentic freshwater habitats in temperate regions exist along a gradient from small ephemeral ponds to large permanent lakes. This environmental continuum is a useful axis for understanding how attributes of individuals ultimately generate structure at the level of the community. Community structure across the gradient is determined by both (a) physical factors, such as pond drying and winter anoxia, that limit the potential breadth of species distributions, and (b) biotic effects mediated by ecological interactions, principally predation, that determine the realized success of species. Fitness tradeoffs associated with a few critical traits of individuals often form the basis for species turnover along the gradient. Among species that inhabit temporary ponds, distributions are often constrained because traits that enhance developmental rate and competitive ability also increase susceptibility to predators. In permanent ponds, changes in the composition of major predators over the gradient limit distributions of prey species because traits that reduce mortality risk in one region of the gradient cause increased risk in other regions of the gradient. Integrated across the gradient, these patterns in species success generate distinct patterns in community structure. Additionally, spatial heterogeneity among habitats along the gradient and the fitness tradeoffs created by this heterogeneity may hold important evolutionary implications for habitat specialization and lineage diversification in aquatic taxa.
SEX DETERMINATION, SEX RATIOS, AND GENETIC CONFLICT
Authors: Werren John H. , Beukeboom Leo W.
Published: July 2002

▪ Abstract  Genetic mechanisms of sex determination are unexpectedly diverse and change rapidly during evolution. We review the role of genetic conflict as the driving force behind this diversity and turnover. Genetic conflict occurs when different components of a genetic system are subject to selection in opposite directions. Conflict may occur between genomes (including paternal-maternal and parental-zygotic conflicts) or within genomes (between cytoplasmic and nuclear genes or sex chromosomes and autosomes). The sex-determining system consists of parental sex-ratio genes, parental-effect sex determiners, and zygotic sex determiners, which are subject to different selection pressures because of differences in their modes of inheritance and expression. Genetic conflict theory is used to explain the evolution of several sex-determining mechanisms, including sex chromosome drive, cytoplasmic sex-ratio distortion, and cytoplasmic male sterility in plants. Although still limited, there is growing evidence that genetic conflict could be important in the evolution of sex-determining mechanisms.
Harvester Ants (Pogonomyrmexspp.): Their Community and Ecosystem Influences
Authors: MacMahon James A. , Mull John F. , Crist Thomas O.
Published: July 2002

▪ Abstract  We summarize the influences of harvester ants of the genus Pogonomyrmex on communities and ecosystems. Because of nest densities, the longevity of nests, and the amount of seed harvested and soil handled, harvester ants have significant direct and indirect effects on community structure and ecosystem functioning. Harvester ants change plant species composition and diversity near their nests. These changes result from differential seed predation by the ants, their actions as seed dispersers and competitors with other granivores, and the favorable soil conditions they create through their digging. Their nest building creates islands of increased nutrient density. In some areas, the effects of their activities may be so pervasive that plant community structure is strongly influenced. Ant removal studies, which would reveal their total impact, have generally not been done. Granivore removals have been conducted in North America where ants are of lesser importance than small mammals, in contrast to other areas (except Israel) where ants are dominant granivores. We review the influence of harvester ants on their competitors, predators, and nest associates, and catalog the factors that influence their foraging patterns and consequently their local distribution.

The harvesting habit in ants since it was first scientifically confirmed by Moggridge has excited an exceptional degree of interest and surprise. But in truth, when one considers all the conditions, the wonder is that it is not more widely distributed.

     Henry Christopher McCook ( 138 , p. 116)
MY EDUCATION IN MINERAL (ESPECIALLY OIL) ECONOMICS
Authors: Adelman M. A.
Published: July 2002

[Figure: see text]

▪ Abstract  The crude oil and natural gas markets have a long colorful history. To understand them, one needs some economic theory. The dominant view, of a fixed mineral stock, implies that a unit produced today means one less in the future. As mankind approaches the limit, it must exert ever more effort per unit recovered. This concept is false, whether stated as common sense or as elegant theory. Under competition, the price results from endless struggle between depletion and increasing knowledge. But sellers may try to control the market in order to offer less and charge more. The political results may feed back upon market behavior. These factors—depletion, knowledge, monopoly, and politics—must be analyzed separately before being put together to capture a slice of a changing history.
STORAGE OFFOSSILFUEL-DERIVEDCARBONDIOXIDEBENEATH THESURFACE OF THEEARTH
Authors: Holloway Sam
Published: July 2002

▪ Abstract  Underground storage in porous and permeable reservoir rocks is a technically feasible way to dispose of industrial quantities of carbon dioxide such as are produced by a fossil fuel–fired power plant. All the necessary steps are commercially proven and in use today. Extensive, naturally occurring CO2accumulations indicate that under favorable conditions CO2can be retained in underground reservoirs for millions of years. Large-scale commercial underground CO2sequestration has begun at the Sleipner West gas field in the North Sea. Some of the major issues to be addressed if this technology is to make an impact on CO2emissions to the atmosphere are cost of CO2capture, safety and security of storage, and public acceptability.
PERITROPHIC MATRIX STRUCTURE AND FUNCTION
Authors: Lehane M. J.
Published: July 2002

▪ Abstract  Formed of proteins, glycoproteins, and chitin microfibrils in a proteoglycan matrix, the peritrophic matrix (PM) separates the food from the midgut epithelium in most but not all insects. A PM occurs in two forms. A type I PM is delaminated from the entire midgut epithelium and, in some cases, may only be formed in response to feeding and the type of meal ingested. A type II PM is produced by a specialized region of the anterior midgut called the cardia and forms a continuous sleeve (or sleeves) that is always present. As it is positioned between food and midgut epithelium, the PM plays key roles in the intestinal biology of the insect. The PM may protect the midgut epithelium from mechanical damage and insult from pathogens and toxins; it must act as a semipermeable membrane regulating passage of molecules between the different midgut compartments; and it may separate the midgut lumen into different, physiologically significant compartments.
Biodiversity of Stream Insects: Variation at Local, Basin, and Regional Scales
Authors: Vinson Mark R. , Hawkins Charles P.
Published: July 2002

▪ Abstract  We review the major conceptual developments that have occurred over the last 50 years concerning the factors that influence insect biodiversity in streams and examine how well empirical descriptions and theory match. Stream insects appear to respond to both spatial and temporal variation in physical heterogeneity. At all spatial scales, the data largely support the idea that physical complexity promotes biological richness, although exceptions to this relationship were found. These exceptions may be related to how we measure habitat complexity at finer spatial scales and to factors that influence regional richness, such as biogeographic history, at broader spatial scales. However, the degree to which local stream insect assemblages are influenced by regional processes is largely unknown.
ERADICATION AND PEST MANAGEMENT
Authors: Myers Judith H. , Savoie Anne , Randen Ed van
Published: July 2002

▪ Abstract  Eradication is the elimination of every single individual of a species from an area to which recolonization is unlikely to occur. Cost-benefit analyses of eradication programs involve biases that tend to underestimate the costs and overestimate the benefits. In this review, we (a) highlight limitations of current cost-benefit analyses, (b) assess eradication strategies from biological and sociological perspectives by discussing particular cases of successful and failed eradication efforts, and (c) briefly contrast eradication and ongoing area-wide control as pest management strategies. Two successful eradication programs involve the screwworm and cattle ticks. Gypsy moth and medfly eradication programs have not been successful, and subsequent captures of insects recur in eradication areas. In situations where heterogeneity of land use patterns make it difficult to prevent reinvasion of the pest, education and area-wide suppression are probably more realistic goals than eradication.
Social Wasp (Hymenoptera: Vespidae) Foraging Behavior
Authors: Richter M. Raveret
Published: July 2002

▪ Abstract  Social wasps (Hymenoptera: Vespidae) forage for water, pulp, carbohydrates, and animal protein. When hunting, social wasps are opportunistic generalists and use a variety of mechanisms to locate and choose prey. Individual foragers are influenced by past foraging experience and by the presence of other foragers on resources. A forager’s ability to learn odors and landmarks, which direct its return to foraging sites, and to associate cues such as odor or leaf damage with resource availability provide the behavioral foundation for facultative specialization by individual foragers. Social wasps, by virtue of their behavior and numbers, have a large impact on other organisms by consuming them directly. Indirect effects such as disruption of prey and resource depletion may also be important. Community-level impacts are particularly apparent when wasps feed upon clumped prey vulnerable to depredation by returning foragers, or when species with large, long-lived colonies are introduced into island communities. A clearer understanding of these relationships may provide insight into impacts of generalist predators on the evolution of their prey.
THEEVOLUTION OFCOLORVISION ININSECTS
Authors: Briscoe Adriana D. , Chittka Lars
Published: July 2002

▪ Abstract  We review the physiological, molecular, and neural mechanisms of insect color vision. Phylogenetic and molecular analyses reveal that the basic bauplan, UV-blue-green-trichromacy, appears to date back to the Devonian ancestor of all pterygote insects. There are variations on this theme, however. These concern the number of color receptor types, their differential expression across the retina, and their fine tuning along the wavelength scale. In a few cases (but not in many others), these differences can be linked to visual ecology. Other insects have virtually identical sets of color receptors despite strong differences in lifestyle. Instead of the adaptionism that has dominated visual ecology in the past, we propose that chance evolutionary processes, history, and constraints should be considered. In addition to phylogenetic analyses designed to explore these factors, we suggest quantifying variance between individuals and populations and using fitness measurements to test the adaptive value of traits identified in insect color vision systems.
Invasions by Insect Vectors of Human Disease
Authors: Lounibos L. Philip
Published: July 2002

▪ Abstract  Nonindigenous vectors that arrive, establish, and spread in new areas have fomented throughout recorded history epidemics of human diseases such as malaria, yellow fever, typhus, and plague. Although some vagile vectors, such as adults of black flies, biting midges, and tsetse flies, have dispersed into new habitats by flight or wind, human-aided transport is responsible for the arrival and spread of most invasive vectors, such as anthropophilic fleas, lice, kissing bugs, and mosquitoes. From the fifteenth century to the present, successive waves of invasion of the vector mosquitoes Aedes aegypti, the Culex pipiens Complex, and, most recently, Aedes albopictus have been facilitated by worldwide ship transport. Aircraft have been comparatively unimportant for the transport of mosquito invaders. Mosquito species that occupy transportable container habitats, such as water-holding automobile tires, have been especially successful as recent invaders. Propagule pressure, previous success, and adaptations to human habits appear to favor successful invasions by vectors.
AIR-WATER GAS EXCHANGE
Authors: Jähne B. , Haußecker H.
Published: July 2002

▪ Abstract  The exchange of inert and sparingly soluble gases—including carbon dioxide, methane, and oxygen—between the atmosphere and oceans is controlled by a thin 20- to 200-μm-thick boundary layer at the top of the ocean. The hydrodynamics in this layer are significantly different from boundary layers at rigid walls, since the orbital motion of the waves is of the same order as the velocities in the viscous boundary layer. Laboratory and field measurements show that wind waves significantly increase the gas transfer rate and that it is significantly influenced in this way by surfactants. Because of limited experimental techniques, the mechanisms for this enhancement and the structure of the turbulence in the boundary layer at a wavy water surface are still not known. A number of new imaging techniques are described that give direct insight into the processes and promise to trigger substantial theoretical progress in the near future.
INTERACTION BETWEEN POROUS MEDIA AND WAVE MOTION
Authors: Chwang A. T. , Chan A. T.
Published: July 2002

▪ Abstract  This article reviews the use of Darcy's law for analyzing waves moving past a porous structure. The engineering applications of these analyses are emph asized. The first part of the article studies theories on the effect of a porous structure on incoming wave trains. It also reviews the movement of waves past a plate with regular gaps in it in an attempt to compare the results of potential theory with those of Darcy's law. The second part reviews the use of a porous structure as a wavemaker when the structure is subject to horizontal oscillation. The third part extends the theories to the use of a porous structure as a breakwater in a two-dimensional harbor. The effect of the structure on reducing waves and suppressing harbor resonance is investigated.
DROP AND SPRAY FORMATION FROM A LIQUID JET
Authors: Lin S. P. , Reitz R. D.
Published: July 2002

▪ Abstract  A liquid jet emanating from a nozzle into an ambient gas is inherently unstable. It may break up into drops of diameters comparable to the jet diameter or into droplets of diameters several orders of magnitude smaller. The sizes of the drops formed from a liquid jet without external control are in general not uniform. The sizes as well as the size distribution depend on the range of flow parameters in which the jet is produced. The jet breakup exhibits different characteristics in different regimes of the relevant flow parameters because of the different physical mechanisms involved. Some recent works based on linear stability theories aimed at the delineation of the different regimes and elucidation of the associated physical mechanisms are reviewed, with the intention of presenting current scientific knowledge on the subject. The unresolved scientific issues are pointed out.
MODELING OF FLUID-STRUCTURE INTERACTION
Authors: Dowell Earl H , Hall Kenneth C
Published: July 2002

▪ Abstract  The interaction of a flexible structure with a flowing fluid in which it is submersed or by which it is surrounded gives rise to a rich variety of physical phenomena with applications in many fields of engineering, for example, the stability and response of aircraft wings, the flow of blood through arteries, the response of bridges and tall buildings to winds, the vibration of turbine and compressor blades, and the oscillation of heat exchangers. To understand these phenomena we need to model both the structure and the fluid. However, in keeping with the overall theme of this volume, the emphasis here is on the fluid models. Also, the applications are largely drawn from aerospace engineering although the methods and fundamental physical phenomena have much wider applications. In the present article, we emphasize recent developments and future challenges. To provide a context for these, the article begins with a description of the various physical models for a fluid undergoing time-dependent motion, then moves to a discussion of the distinction between linear and nonlinear models, time-linearized models and their solution in either the time or frequency domains, and various methods for treating nonlinear models, including time marching, harmonic balance, and systems identification. We conclude with an extended treatment of the modal character of time-dependent flows and the construction of reduced-order models based on an expansion in terms of fluid modes. The emphasis is on the enhanced physical understanding and dramatic reductions in computational cost made possible by reduced-order models, time linearization, and methodologies drawn from dynamical system theory.
Genetic Analysis of Calmodulin and Its Targets in Saccharomyces cerevisiae
Authors: Cyert Martha S.
Published: July 2002

▪ Abstract  Calmodulin, a small, ubiquitous Ca2+-binding protein, regulates a wide variety of proteins and processes in all eukaryotes. CMD1, the single gene encoding calmodulin in S. cerevisiae, is essential, and this review discusses studies that identified many of calmodulin's physiological targets and their functions in yeast cells. Calmodulin performs essential roles in mitosis, through its regulation of Nuf1p/Spc110p, a component of the spindle pole body, and in bud growth, by binding Myo2p, an unconventional class V myosin required for polarized secretion. Surprisingly, mutant calmodulins that fail to bind Ca2+ can perform these essential functions. Calmodulin is also required for endocytosis in yeast and participates in Ca2+-dependent, stress-activated signaling pathways through its regulation of a protein phosphatase, calcineurin, and the protein kinases, Cmk1p and Cmk2p. Thus, calmodulin performs important physiological functions in yeast cells in both its Ca2+-bound and Ca2+-free form.
Patterns of Genetic Variation in Mendelian and Complex Traits
Authors: Zwick Michael E. , Cutler David J. , Chakravarti Aravinda
Published: July 2002

This review discusses the prospects for understanding the genetic basis of complex traits in humans. We take the view that work done on Drosophila melanogaster can serve as a model for understanding complex traits in humans, and the literature on this model system, as well as on humans, is reviewed. The prospects for success in understanding the genetic basis of complex traits depend, in part, on the nature of the forces acting on genetic variation. We suggest that different experimental approaches should be undertaken for traits caused by common genetic variants versus those arising from rare genetic variants.
THE NF-κB AND IκB PROTEINS: New Discoveries and Insights
Authors: Baldwin Albert S.
Published: July 2002

▪ Abstract  The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases. A primary level of control for NF-κB is through interactions with an inhibitor protein called IκB. Recent evidence confirms the existence of multiple forms of IκB that appear to regulate NF-κB by distinct mechanisms. NF-κB can be activated by exposure of cells to LPS or inflammatory cytokines such as TNF or IL-1, viral infection or expression of certain viral gene products, UV irradiation, B or T cell activation, and by other physiological and nonphysiological stimuli. Activation of NF-κB to move into the nucleus is controlled by the targeted phosphorylation and subsequent degradation of IκB. Exciting new research has elaborated several important and unexpected findings that explain mechanisms involved in the activation of NF-κB. In the nucleus, NF-κB dimers bind to target DNA elements and activate transcription of genes encoding proteins involved with immune or inflammation responses and with cell growth control. Recent data provide evidence that NF-κB is constitutively active in several cell types, potentially playing unexpected roles in regulation of gene expression. In addition to advances in describing the mechanisms of NF-κB activation, excitement in NF-κB research has been generated by the first report of a crystal structure for one form of NF-κB, the first gene knockout studies for different forms of NF-κB and of IκB, and the implications for therapies of diseases thought to involve the inappropriate activation of NF-κB.
REGULATION OF IMMUNE RESPONSES BY TGF-β
Authors: Letterio John J. , Roberts Anita B.
Published: July 2002

▪ Abstract  The transforming growth factor β (TGF-β) family of proteins are a set of pleiotropic secreted signaling molecules with unique and potent immunoregulatory properties. TGF-β1 is produced by every leukocyte lineage, including lymphocytes, macrophages, and dendritic cells, and its expression serves in both autocrine and paracrine modes to control the differentiation, proliferation, and state of activation of these immune cells. TGF-β can modulate expression of adhesion molecules, provide a chemotactic gradient for leukocytes and other cells participating in an inflammatory response, and inhibit them once they have become activated. Increased production and activation of latent TGF-β have been linked to immune defects associated with malignancy and autoimmune disorders, to susceptibility to opportunistic infection, and to the fibrotic complications associated with chronic inflammatory conditions. In addition to these roles in disease pathogenesis, TGF-β is now established as a principal mediator of oral tolerance and can be recognized as the sine qua non of a unique subset of effector cells that are induced in this process. The accumulated knowledge gained through extensive in vitro functional analyses and from in vivo animal models, including newly established TGF-β gene knockout and transgenic mice, supports the concept that clinical therapies based on modulation of this cytokine represent an important new approach to the treatment of disorders of immune function.
CD8+ T Cell Effector Mechanisms in Resistance to Infection
Authors: Harty John T. , Tvinnereim Amy R. , White Douglas W.
Published: July 2002

Based on T cell subset depletion studies and the analysis of gene knockout mice, it is evident that CD8+T cells contribute to resistance against intracellular infections with certain viral, protozoan, and bacterial pathogens. Although they are known primarily for their capacity to kill infected cells, CD8+T cells elaborate a variety of effector mechanisms with the potential to defend against infection. Microbes use multiple strategies to cause infection, and the nature of the pathogenhost interaction may determine which CD8+T cell effector mechanisms are required for immunity. In this review, we summarize our current understanding of the effector functions used by CD8+T cells in resistance to pathogens. Analyses of mice deficient in perforin and/or Fas demonstrate that cytolysis is critical for immunity against some, but not all, infections and also reveal the contribution of cytolysis to the pathogenesis of disease. The role of CD8+T cell–derived cytokines in resistance to infection has been analyzed by systemic treatment with neutralizing antibodies and cytokine gene knockout mice. These studies are complicated by the fact that few, if any, cytokines are uniquely produced by CD8+T cells. Thus, the requirement for CD8+T cell– derived cytokines in resistance against most pathogens remains to be defined. Finally, recent studies of human CD8+T cells reveal the potential for novel effector mechanisms in resistance to infection.
Regulatory T Cells in Autoimmmunity
Authors: Shevach Ethan M.
Published: July 2002

Clonal deletion of autoreactive T cells in the thymus is not the sole mechanism for the induction of tolerance to self-antigens since partial depletion of peripheral CD4+T cells from neonatal and adult animals results in the development of organ-specific autoimmunity. Reconstitution of these immunodeficient animals with populations of regulatory CD4+T cells prevents the development of autoimmunity. The lineage of regulatory CD4+T cells is generated in the thymus and can be distinguished from effector cells by the expression of unique membrane antigens. The target antigens for these suppressor populations and their mechanisms of action remain poorly defined. Depletion of regulatory T cells may be useful in the induction of immunity to weak antigens, such as tumor-specific antigens. Conversely, enhancement of regulatory T cell function may be a useful adjunct to the therapy of autoimmune diseases and for prevention of allograft rejection.
Regulation of Antibody Responses via Antibodies, Complement, and Fc Receptors
Authors: Heyman Birgitta
Published: July 2002

Antibodies can completely suppress or enhance the antibody response to their specific antigen by several hundredfold. Immunoglobulin M (IgM) enhances antibody responses via the complement system, and complement activation by IgM probably starts the chain of events leading to antibody responses to suboptimal antigen doses. IgG can enhance primary antibody responses in the absence of the complement system and seems to be dependent on Fc receptors for IgG (FcγRs). IgE enhances antibody responses via the low-affinity receptor for IgE (FcεRII/CD23). The precise effector mechanisms that cause enhancement are not known, but direct B-cell signaling, antigen presentation, and increased follicular localization are all possibilities. IgG, IgE, and IgM may also suppress antibody responses when used in certain immunization regimes, and it seems reasonable that an important mechanism behind suppression is the masking of antigenic epitopes by antibodies. In addition, FcγRIIB, which contains a cytoplasmic inhibitory motif, acts as a negative regulator of antibody responses. This receptor, however, may prevent the antibody responses from exceeding a certain level rather than causing complete suppression.
Chemokine Signaling and Functional Responses: The Role of Receptor Dimerization and TK Pathway Activation
Authors: Mellado Mario , Rodríguez-Frade José Miguel , Mañes Santos , Martínez-A Carlos
Published: July 2002

A broad array of biological responses, including cell polarization, movement, immune and inflammatory responses, and prevention of HIV-1 infection, are triggered by the chemokines, a family of structurally related chemoattractant proteins that bind to specific seven-transmembrane receptors linked to G proteins. Here we discuss one of the early signaling pathways activated by chemokines, the JAK/STAT pathway. Through this pathway, and possibly in conjunction with other signaling pathways, the chemokines promote changes in cellular morphology, collectively known as polarization, required for chemotactic responses. The polarized cell expresses the chemokine receptors at the leading cell edge, to which they are conveyed by rafts, a cholesterol-enriched membrane fraction fundamental to the lateral organization of the plasma membrane. Finally, the mechanisms through which the chemokines promote their effect are discussed in the context of the prevention of HIV-1 infection.
CTLA-4-Mediated Inhibition in Regulation of T Cell Responses: Mechanisms and Manipulation in Tumor Immunotherapy
Authors: Chambers Cynthia A. , Kuhns Michael S. , Egen Jackson G. , Allison James P.
Published: July 2002

The T cell compartment of adaptive immunity provides vertebrates with the potential to survey for and respond specifically to an incredible diversity of antigens. The T cell repertoire must be carefully regulated to prevent unwanted responses to self. In the periphery, one important level of regulation is the action of costimulatory signals in concert with T cell antigen-receptor (TCR) signals to promote full T cell activation. The past few years have revealed that costimulation is quite complex, involving an integration of activating signals and inhibitory signals from CD28 and CTLA-4 molecules, respectively, with TCR signals to determine the outcome of a T cell's encounter with antigen. Newly emerging data suggest that inhibitory signals mediated by CTLA-4 not only can determine whether T cells become activated, but also can play a role in regulating the clonal representation in a polyclonal response. This review primarily focuses on the cellular and molecular mechanisms of regulation by CTLA-4 and its manipulation as a strategy for tumor immunotherapy.
Negative Regulation of Immunoreceptor Signaling
Authors: Veillette André , Latour Sylvain , Davidson Dominique
Published: July 2002

Immune cells are activated as a result of productive interactions between ligands and various receptors known as immunoreceptors. These receptors function by recruiting cytoplasmic protein tyrosine kinases, which trigger a unique phosphorylation signal leading to cell activation. In the recent past, there has been increasing interest in elucidating the processes involved in the negative regulation of immunoreceptor-mediated signal transduction. Evidence is accumulating that immunoreceptor signaling is inhibited by complex and highly regulated mechanisms that involve receptors, protein tyrosine kinases, protein tyrosine phosphatases, lipid phosphatases, ubiquitin ligases, and inhibitory adaptor molecules. Genetic evidence indicates that this inhibitory machinery is crucial for normal immune cell homeostasis.
Antigen Presentation and T Cell Stimulation by Dendritic Cells
Authors: Guermonprez Pierre , Valladeau Jenny , Zitvogel Laurence , Théry Clotilde , Amigorena Sebastian
Published: July 2002

Dendritic cells take up antigens in peripheral tissues, process them into proteolytic peptides, and load these peptides onto major histocompatibility complex (MHC) class I and II molecules. Dendritic cells then migrate to secondary lymphoid organs and become competent to present antigens to T lymphocytes, thus initiating antigen-specific immune responses, or immunological tolerance. Antigen presentation in dendritic cells is finely regulated: antigen uptake, intracellular transport and degradation, and the traffic of MHC molecules are different in dendritic cells as compared to other antigen-presenting cells. These specializations account for dendritic cells' unique role in the initiation of immune responses and the induction of tolerance.
LIQUID CRYSTAL MATERIALS AND LIQUID CRYSTAL DISPLAYS
Authors: Schadt Martin
Published: July 2002

▪ Abstract  Since the early 1970s, three major prerequisites have brought the success of the liquid crystal display (LCD) technology to its key role of today. Namely, the discovery of electro-optical field-effects on which the displays are based, the successful search for liquid crystals (LCs) with material properties that meet the complex requirements of electro-optical effects and render the effects applicable in displays, and last but not least, the development of the technological tools required for manufacturing displays.

Virtually all of today's commercial LCDs are based on the twisted nematic (TN) or on various supertwisted nematic (STN) effects whose extensive development and improvement over the past 25 years is still rapidly progressing. Those liquid crystal material properties and electro-optical effects that essentially determine the performance of nematic displays are reviewed. Correlations between molecular functional structural groups, LC material properties, and their electro-optical relevance for TN and STN displays are outlined. Included are dual-frequency addressing phenomena in liquid crystal materials, in situ dielectric heating of displays, and conductivity phenomena that are related and that may either hamper or improve the performance of high-information content LCDs. Moreover, we review some recent developments made in our laboratories on novel electro-optical devices and device-specific functional organic materials, e.g. optical alignment of monomeric and polymeric liquid crystals by linearly polarized light; the generation of photo-patterned multidomain twisted nematic displays with broad field of view; the operation of displays with circularly polarized light, as well as compact and bright cholesteric LCD projection optics whose polarizers, filters, and modulators are all based on liquid crystal elements.
MAGNETIC FORCE MICROSCOPY
Authors: Hartmann U.
Published: July 2002

▪ Abstract  This review on magnetic force microscopy does not provide an exhaustive overview of the past accomplishments of the method but rather discusses the present state of the art. Magnetic force microscopy is a special mode of noncontact operation of the scanning force microscope. This mode is realized by employing suitable probes and utilizing their specific dynamic properties. The particular material composition of the probes and the dynamic mode of their operation are discussed in detail. The interpretation of images acquired by magnetic force microscopy requires some basic knowledge about the specific near-field magnetostatic interaction between probe and sample. The general magnetostatics as well as convenient simplifications of the general theory, which often can be used in practice, are summarized. Applications of magnetic force microscopy in the magnetic recording industry and in the fundamental research on magnetic materials are discussed in terms of representative examples. An important aspect for any kind of microscopy is the ultimately achievable spatial resolution and inherent restrictions in the application of the method. Both aspects are considered, and resulting prospects for future methodical improvements are given.
HIRUDIN: Clinical Potential of a Thrombin Inhibitor
Authors: Johnson, Ph.D Paul H.
Published: July 2002

▪ Abstract  Hirudin is the most potent and specific known inhibitor of thrombin, the enzyme that plays a key regulatory function in hemostasis and blood coagulation. The importance of thrombosis in cardiovascular disease has recently highlighted the limitations of existing antithrombotic drugs and the potential value of direct thrombin inhibition as an effective approach to antithrombotic therapy. Hirudin and a small peptidomimetic analog—hirulog—are being developed as alternatives to heparin for the treatment of unstable angina, for prevention of abrupt closure and restenosis following coronary angioplasty, for prevention of deep vein thrombosis after major orthopedic surgery, and as an adjunct to fibrinolytic therapy. Direct thrombin inhibitors have several potential advantages over heparin: They can inhibit thrombin bound to clots or extracellular matrices, which are relatively resistant to heparin; they do not require antithrombin III as a cofactor, which may lead to a more predictable dose response; and they are not inhibited by activated platelets, which release platelet factor 4 and other molecules that neutralize heparin. The results of early clinical studies suggest that hirudin and hirulog may be more efficacious and more predictable and may have fewer bleeding complications than heparin for several clinical indications.
BRAIN IMAGING IN SCHIZOPHRENIA
Authors: Kotrla, M.D Kathyrn J. , Weinberger, M.D Daniel R.
Published: July 2002

▪ Abstract  Neuroimaging provides an unprecedented means by which to study psychiatric disorders. Structural imaging methods, i.e. computerized tomography (CT) and magnetic resonance imaging (MRI), have revealed subtle differences in the brains of schizophrenic patients that appear to be present before symptom onset. Radionuclide functional methods such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) have led to hypotheses about dysfunction in specific neuronal networks in schizophrenia. New advances in MRI allow functional data to be obtained noninvasively in a single individual using conventional MRI scanners. This chapter discusses the parallels between the historical technical developments in neuroimaging and the deepening understanding of the etiology and manifestations of schizophrenia.
PHARMACOLOGIC ENHANCEMENT OF WOUND HEALING
Authors: Pierce, Ph.D., M.D Glenn F. , Mustoe, M.D Thomas A.
Published: July 2002

▪ Abstract  The field of pharmacologic modulation of soft tissue repair is in its infancy. Although the soluble, cellular, and insoluble mediators that govern repair have not been elucidated, the application of pharmacologic concentrations of purified polypeptide growth factors, cytokines, and matrix molecules has nonetheless resulted in the acceleration of normal repair and the reversal of deficient repair in a wide variety of dermal wound models in animals. However, early clinical results using these factors have been less than encouraging, and their potential roles in the armamentarium of chronic wound therapies remain to be established.
NEUROPSYCHIATRIC CONSEQUENCES OF STROKE
Authors: Robinson, MD Robert G.
Published: July 2002

▪ Abstract  Numerous emotional and behavioral disorders occur following cerebrovascular lesions. Depression is the most common of these, affecting up to 40% of patients. Clinical correlates of post-stroke depression include severity of physical and cognitive impairment as well as location of brain injury. Perhaps the most compelling reason to identify post-stroke depression, however, is its substantial impact on recovery in activities of daily living, cognitive function, and survival. Antidepressant medication has been shown to effectively treat depression, although its administration may require careful clinical monitoring. Other post-stroke emotional/behavioral disorders include mania, bipolar disorder, anxiety disorder, apathy, and pathological crying. Controlled studies have not documented the effect of these disorders on long-term recovery, but the potential impact of syndromes such as mania and apathy on rehabilitation efforts or pathological crying on social functioning are evident. With the exception of pathological crying, which has been shown to respond to antidepressant drug therapy, the other post-stroke emotional/behavioral disorders need to be evaluated in controlled treatment trials for response to therapy.
PARVOVIRUS B19 IN HUMAN DISEASE
Authors: Brown, MD K.E. , Young, MD N.S.
Published: July 2002

▪ Abstract  Parvovirus B19, the only known human pathogenic parvovirus, is associated with a wide range of disease manifestations. In healthy individuals, the major presentation of B19 infection is erythema infectiosum. In patients with underlying hemolytic disorders, infection is the primary cause of transient aplastic crisis. In immunosuppressed patients, persistent infection may develop that presents as pure red cell aplasia and chronic anemia. In utero infection may result in hydrops fetalis or congenital anemia. Diagnosis is based on examination of bone marrow and virologic studies. Much is known of the pathophysiology of the virus, and studies are in progress to develop a vaccine to prevent this widespread infection.
Chronic Fatigue Syndrome: An Update
Authors: Komaroff A. L. , Buchwald, MD D. S.
Published: July 2002

Among the many patients who seek medical care for the complaint of fatigue, a small number suffer from chronic fatigue syndrome (CFS). CFS is a poorly understood condition characterized by debilitating fatigue and associated symptoms lasting at least six months. Studies indicate that the illness is not simply a manifestation of an underlying psychiatric disorder, but rather is an illness characterized by activation of the immune system, various abnormalities of several hypothalamic-pituitary axes, and reactivation of certain infectious agents.
New Horizons in the Treatment of Autoimmune Diseases: Immunoablation and Stem Cell Transplantation
Authors: Marmont Alberto M.
Published: July 2002

▪ Abstract  The prevalence of autoimmune diseases (ADs) in Western countries is estimated to be from 3–7%, and the treatment of severe, relapsing/refractory cases is still not satisfactory. The concept of utilizing intense immunosuppression followed by allogeneic or even autologous hemolymphopoietic stem cells (HSCs) to treat AD is based on encouraging results in experimental animals and from serendipitous cases of patients with both ADs and malignancies who were allotransplanted for the latter. However, rare unexpected relapses despite donor immune engraftment have been reported following HSC transplantation for AD. Autologous transplantation is a more feasible procedure with lower toxicity than allogeneic transplantation. This article analyzes the experimental basis for stem cell transplantation in AD and discusses the most important clinical results of both allogeneic and autologous HSC transplants.
Pathophysiological Role of Cytokines in Congestive Heart Failure
Authors: Blum Arnon , Miller Hylton
Published: July 2002

▪ Abstract  Heart failure is a complex neurohumoral and inflammatory syndrome. Recent studies have shown that proinflammatory cytokines (interleukin-1, interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor) are involved in cardiac depression and in the complex syndrome of heart failure. Understanding the involvement of these cytokines may enable us to reverse cardiac depression and heart failure by the use of monoclonal antibodies directed against specific cytokines to block the downhill progression of heart failure.