bluuebunny/crossref_metadata_2025 huggingface dataset:
COROTATING AND TRANSIENT SOLAR WIND FLOWS IN THREE DIMENSIONS
Authors: Gosling J. T.
Published: July 2002

▪ Abstract  Two types of flows dominate the large-scale structure of the solar wind: corotating flows and transient disturbances. Corotating flows are associated with spatial variability in the coronal expansion and solar rotation, whereas transient disturbances are associated with episodic ejections of material into interplanetary space from coronal regions not previously participating in the solar wind expansion. Ulysses' recent epic journey over the poles of the Sun has provided new insights on the three-dimensional nature of both corotating flows and transient disturbances in the solar wind and their evolution with heliocentric distance and latitude. This paper provides a simple physical description of the origins and dynamics of both of these types of solar wind flows, highlighting new understanding gained from the unique Ulysses high-latitude observations.
MODELING EXTRAGALACTIC JETS
Authors: Ferrari Attilio
Published: July 2002

▪ Abstract  Extragalactic jets were discovered and initially studied by radio astronomers in connection with extended radio sources. At present, the combination of jets and disks is considered the crucial element in unification models for all active galactic nuclei (AGNs). The acceleration and propagation conditions of jets, together with the aspect ratio of the disk/jet geometry with respect to the observer, shape the morphologies of AGNs. However, these phenomenological models are very complex from the physical and mathematical point of view, as they involve different elements of the theories of gravitation, fluid dynamics, and electrodynamics in a highly nonlinear combination and in conditions not easily reproducible in laboratory plasma or fluid experiments. In the last ten years, theorists have attacked the subject with advanced analytical and numerical methods, and some important results have already been established that confirm the global scenario, although we are still far from a complete physical interpretation. This review summarizes the main results on the art of jet modeling, emphasizing the limitations of the available models and the possibility of new developments.
POLYADENYLATION OF mRNA IN PROKARYOTES
Authors: Sarkar Nilima
Published: July 2002

The 3′-ends of both prokaryotic and eukaryotic mRNA are polyadenylated, but the poly(A) tracts of prokaryotic mRNA are generally shorter, ranging from 15 to 60 adenylate residues and associated with only 2–60% of the molecules of a given mRNA species. The sites of polyadenylation of bacterial mRNA are diverse and include the 3′-ends of primary transcripts, the sites of endonucleolytic processing in the 3′ untranslated and intercistronic regions, and sites within the coding regions of mRNA degradation products. The diversity of polyadenylation sites suggests that mRNA polyadenylation in prokaryotes is a relatively indiscriminate process that can occur at all mRNA's 3′-ends and does not require specific consensus sequences as in eukaryotes. Two poly(A) polymerases have been identified in Escherichia coli. They are encoded by unlinked genes, neither of which is essential for growth, suggesting significant functional overlap. Polyadenylation promotes the degradation of a regulatory RNA that inhibits the replication of bacterial plasmids and may play a similar role in the degradation of mRNA. However, under certain conditions, poly(A) tracts may lead to mRNA stabilization. Their ability to bind S1 ribosomal protein suggests that poly(A) tracts may also play a role in mRNA translation.
Quantitative Measurement and Prediction of Biophysical Response During Freezing in Tissues
Authors: Bischof John C.
Published: July 2002

▪ Abstract  Cryopreservation and cryosurgery are important biomedical applications used to selectively preserve or destroy cellular systems through freezing. Studies using cryomicroscopy techniques, which allow the visualization of the freezing process in single cells, have shown that a drop in viability correlates with the extent of two biophysical events during the freezing process: (a) intracellular ice formation and (b) cellular dehydration. These same biophysical events operate in tissue systems; however, the inability to visualize and quantify the dynamics of the freezing process in tissues has hampered direct correlation of these events with freezing-induced changes in viability. This review highlights two new techniques that use freeze substitution and differential scanning calorimetry to provide dynamic freezing data in tissue. Characteristic dimensions and parameters extracted from these new data are then used in a predictive model of biophysical freezing response in several tissues, including liver and tumor. This approach promises to help guide improved design of both cryopreservation and cryosurgical applications of tissue freezing.
Three-Dimensional Ultrasound Imaging
Authors: Fenster Aaron , Downey Donal B.
Published: July 2002

▪ Abstract  Two-dimensional viewing of three-dimensional anatomy by conventional ultrasound limits our ability to quantify and visualize a number of diseases and is partly responsible for the reported variability in diagnosis. Over the past two decades, many investigators have addressed this limitation by developing three-dimensional imaging techniques, including three-dimensional ultrasound imaging. In this paper we describe the development of a number of three-dimensional ultrasound imaging systems that make use of B mode, color Doppler, and power Doppler. In these systems, the conventional ultrasound transducer is scanned mechanically or by a freehand technique. The ultrasound images are digitized and then reconstructed into a three-dimensional volume, which can be viewed and manipulated interactively by the diagnostician with a variety of image-rendering techniques. These developments as well as future trends are discussed with regard to their applications and limitations.
Fundamentals Of Impact Biomechanics: Part 2—Biomechanics of the Abdomen, Pelvis, and Lower Extremities
Authors: King Albert I.
Published: July 2002

▪ Abstract  This is the second of two chapters (the first chapter appeared in the Annual Review of Biomedical Engineering, 2000, 2:55–81) dealing with some 60 years of accumulated knowledge in the field of impact biomechanics. The regions covered in the first chapter were the head, neck, and thorax. In this chapter, the abdomen, pelvis, and lower extremities are discussed. The thoracolumbar spine is not covered because of length limitations and the low frequency of injury to this area from automotive accidents. Again, in the cited results, the reader needs to be keenly aware of the wide variation in human response and tolerance. This is due primarily to the large biological variations among humans and to the effects of aging. Average values that are useful in design cannot be applied to individuals.
BACTERIOPHAGE DISPLAY AND DISCOVERY OF PEPTIDE LEADS FOR DRUG DEVELOPMENT
Authors: Lowman H. B.
Published: July 2002

▪ Abstract  Phage display makes large-peptide diversity libraries readily attainable for identifying novel peptide ligands for receptors and other protein or non-protein targets. This technology kindles enthusiasm for the idea that large and protein-protein interaction surfaces (epitopes) can be distilled down to small pharmacophores. These may be accessible to organic scaffolding, yielding new orally active drugs that might otherwise have taken greater time and effort to be discovered through chemical-library screening. This review, though not comprehensive with respect to the explosive volume of phage display work over the last few years, focuses on recent developments in phage-displayed peptide technology.
Extinction Vulnerability and Selectivity: Combining Ecological and Paleontological Views
Authors: McKinney Michael L.
Published: July 2002

Extinction is rarely random across ecological and geological time scales. Traits that make some species more extinction-prone include individual traits, such as body size, and abundance. Substantial consistency appears across ecological and geological time scales in such traits. Evolutionary branching produces phylogenetic (as often measured by taxonomic) nesting of extinction-biasing traits at many scales. An example is the tendency, seen in both fossil and modern data, for higher taxa living in marine habitats to have generally lower species extinction rates. At lower taxononomic levels, recent bird and mammal extinctions are concentrated in certain genera and families. A fundamental result of such selectivity is that it can accelerate net loss of biodiversity compared to random loss of species among taxa. Replacement of vulnerable taxa by rapidly spreading taxa that thrive in human-altered environments will ultimately produce a spatially more homogenized biosphere with much lower net diversity.
The Origin and Early Evolution of Turtles
Authors: Rieppel Olivier , Reisz Robert R.
Published: July 2002

▪ Abstract  A critical reexamination of turtle relationships continues to support a sister-group relationship of turtles with a clade of marine reptiles, Sauropterygia, within crown-group Diapsida (Sauria). The high Homoplasy Index raises concerns about the phylogenetic information content of various morphological characters in broad-scale phylogenetic analyses. Such analyses may also suffer from inadequate statements of primary homology. Several such statements that have played an important role in the analysis of turtle relationships (dermal armor, acromion, astragalo-calcaneal complex, hooked fifth metatarsal) are reviewed in detail. An evolutionary scenario for the origin of the turtle bauplan suggests an aquatic origin of turtles, which is supported not only by their sauropterygian relationships, but also by paleobiogeographic and stratigraphic considerations. However, turtle relationships remain labile, and further investigations of their relationships are required, involving molecular and physiological data.
URBAN CONGESTION: A European Perspective on Theory and Practice
Authors: May A. D. , Nash C. A.
Published: July 2002

▪ Abstract  Growing urban transport congestion is a major cause of environmental problems, as well as delays. One may argue that this is a classic problem of externalities and can be readily corrected by means of the price mechanism. However, although interest is increasing in pricing as an element in any solution, the answer is not so easy. Despite the falling cost of microelectronics, urban road pricing remains complex, expensive to administer, and politically controversial. Nevertheless, modeling exercises and limited practical experience suggest that most, if not all, of these problems can now be overcome and that road pricing may now be successfully implemented. But the continued opposition to road pricing makes consideration of the alternatives necessary. Indeed, both for political and economic reasons, road pricing appears much more likely to be successfully implemented as part of a package of measures than in isolation.
CLIMATE CHANGE MITIGATION IN THE ENERGY AND FORESTRY SECTORS OF DEVELOPING COUNTRIES
Authors: Sathaye Jayant A. , Ravindranath N. H.
Published: July 2002

▪ Abstract  The continued accumulation of greenhouse gases in the atmosphere is expected to severely impact the earth's natural resources and agriculture. Greenhouse gas emissions from the developing world are rising faster than those from other countries, and many studies have noted that it would not be possible to stabilize climate change without reducing the growth of these emissions. Can this be achieved without affecting economic growth and social fabric in these countries? Mitigation studies indicate that if energy efficiency and forestry options are implemented judiciously, emissions can be reduced at a negative cost without affecting economic growth. The studies also suggest that this would increase significantly the worldwide demand for natural gas and renewable technologies. Country studies show that the aggregate mitigation potential in the forestry sector is higher, and the costs per tonne of carbon are lower, than reported earlier by global studies. Barriers to the implementation of energy and forestry options need to be explicitly taken into consideration because these may change the priority of options and the choice of policy measures.
NATURAL SELECTION AT MAJOR HISTOCOMPATIBILITY COMPLEX LOCI OF VERTEBRATES
Authors: Hughes Austin L. , Yeager Meredith
Published: July 2002

▪ Abstract  The loci of the vertebrate major histocompatibility complex encode cell-surface glycoproteins that present peptides to T cells. Certain of these loci are highly polymorphic, and the mechanisms responsible for this polymorphism have been intensely debated. Four independent lines of evidence support the hypothesis that MHC polymorphisms are selectively maintained: (a) The distribution of allelic frequencies does not fit the neutral expectation. (b) The rate of nonsynonymous nucleotide substitution significantly exceeds the rate of synonymous substitution in the codons encoding the peptide-binding region of the molecule. (c) Polymorphisms have been maintained for long periods of time (“trans-species polymorphism”). (d) Introns have been homogenized relative to exons over evolutionary time, suggesting that balancing selection acts to maintain diversity in the latter, in contrast to the former.
THE IMMUNE SYSTEM AS A SUPERSYSTEM
Authors: Tada Tomio
Published: July 2002

I coined a term “supersystem” to designate highly integrated life systems such as the immune system, nervous system, and embryogenesis. While the mechanistic system is defined as a set of diverse elements so connected and related as to form an organic whole for a particular purpose, the “supersystem” engenders its own elements from a single progenitor. The diverse elements thus generated form relationships by mutual adaptation and coadaptation, and thus they create a dynamic self-regulating system through self-organization. It is a closed self-satisfied system, yet open to the environment, receiving outside signals to transduce them into internal messages for self-regulation and expansion. Unlike a mechanistic system, the “supersystem” has no defined purpose and determines its own fate by referring to its self-established behavioral pattern.

Both the immune and nervous systems develop and function as a typical “supersystem.” The prototype of the supersystem can be seen in embryogenesis and evolution. The concept of the supersystem can also be applied to the development of language, or a city, or other cultural phenomena that human beings have created as a result of their vital activities.
NATURALLY OCCURRING PRIMARY DEFICIENCIES OF THE IMMUNE SYSTEM
Authors: Fischer A. , Cavazzana-Calvo M. , Basile G. De Saint , DeVillartay J. P. , Di Santo J. P. , Hivroz C. , Rieux-Laucat F. , Le Deist F.
Published: July 2002

▪ Abstract  Naturally occurring genetic disorders of the immune system provide many models for the study of its development and function. In a way, their analysis complements the information provided by the generation of genetic defects in mice created using homologous recombination techniques. In this review, the recent findings made in three areas are focused upon deficiencies in T cell differentiation and in T lymphocyte activation, and on the control process of peripheral immune response.
CHARACTERIZATION OF ORGANIC THIN FILM MATERIALS WITH NEAR-FIELD SCANNING OPTICAL MICROSCOPY (NSOM)
Authors: Barbara P. F. , Adams D. M. , O'Connor D. B.
Published: July 2002

▪ Abstract  Recent progress on the use of near-field scanning optical microscopy (NSOM) to characterize organic thin film materials is extensively reviewed. NSOM is leading to important new information on the morphology and spatially resolved optical properties of a variety of materials, complementing more widely available methods for thin film analysis. Materials described in this review include polymer thin films, molecular aggregates, molecular crystals, molecular semiconductor heterojunctions, biological materials, and molecular mono-, bi-, and multi-layer films.
NITRIC OXIDE SYNTHASE: Role as a Transmitter/Mediator in the Brain and Endocrine System
Authors: Dawson, M.D., Ph.D Ted M. , Dawson, Ph.D Valina L.
Published: July 2002

▪ Abstract  Nitric oxide is a unique biological messenger molecule. It is produced by endothelial cells to mediate blood vessel relaxation; it mediates, in part, the immune functions of activated macrophages; and in the central and peripheral nervous system it serves as a neurotransmitter. In the nervous system, nitric oxide may regulate neurotransmitter release, it may play a key role in synaptic plasticity and morphogenesis, and it may regulate sexual and aggressive behavior. Under conditions of excessive formation, nitric oxide is emerging as an important neurotoxin.
THE SURGICAL MANAGEMENT OF ATRIAL FIBRILLATION
Authors: Cox, MD James L. , Sundt III, MD Thoralf M.
Published: July 2002

▪ Abstract  Atrial fibrillation is the most common dysrhythmia encountered in clinical practice. For some patients, satisfactory rate control is not possible by pharmacologic means. This led us to develop a surgical approach to its cure, which in turn has led to a deeper understanding of the electrophysiologic basis of atrial fibrillation and to the development of a surgical procedure that is highly effective in restoring sinus rhythm with an acceptable mortality and morbidity. We review these findings as well as the clinical results obtained with the Maze procedure.
Nucleic Acid Transport in Plant-Microbe Interactions: The Molecules That Walk Through the Walls
Authors: Tzfira Tzvi , Rhee Yoon , Chen Min-Huei , Kunik Talya , Citovsky Vitaly
Published: July 2002

▪ Abstract  Many microbes “genetically invade” plants by introducing DNA or RNA molecules into the host cells. For example, plant viruses transport their genomes between host cells, whereas Agrobacterium spp. transfer T-DNA to the cell nucleus and integrate it into the plant DNA. During these events, the transported nucleic acids must negotiate several barriers, such as plant cell walls, plasma membranes, and nuclear envelopes. This review describes the microbial and host proteins that participate in cell-to-cell transport and nuclear import of nucleic acids during infection by plant viruses and Agrobacterium spp. Possible molecular mechanisms by which these transport processes occur are discussed.
Neuropeptides and the Integration of Motor Responses to Dehydration
Authors: Watts Alan G.
Published: July 2002

▪ Abstract  Drinking and eating are critically important motivated behaviors whose expression is usually tightly linked; under conditions of spontaneous intake, disruption of one usually disturbs the other. This characteristic is exemplified by dehydration-induced anorexia in which increasing plasma osmolality leads to a centrally generated reduction in food intake, which is then rapidly reversed as water is again made available. This review discusses, at a systems level, how the brain is organized to generate these behaviors and how dehydration affects the expression of neuropeptides in sets of anatomically defined forebrain circuits that contribute to the integration of motor outputs. These findings are then used to consider how altered neuropeptidergic signaling operates within motor drive networks and how these changes may impact the way neuroendocrine, autonomic, and behavioral motor systems respond to this fundamental homeostatic challenge.
Recent Progress in Neutron Star Theory
Authors: Heiselberg Henning , Pandharipande Vijay
Published: July 2002

▪ Abstract  We review recent progress in the theory of neutron stars and compare its predictions with the observational data on masses, radii, and temperatures. The theory of neutron stars made up of neutrons, protons, and leptons is discussed in detail along with recent models of nuclear forces and modern many-body techniques. The possibilities of pion and kaon condensation in dense neutron star matter are considered, as is the possible occurrence of strange hyperons and quark-matter drops in the stellar core. The structure of mixed-phase matter in neutron stars, as well as the probable effect of phase transitions on the spin down of pulsars, is also discussed.
CHROMIUM AS A SUPPLEMENT
Authors: Lukaski Henry C.
Published: July 2002

▪ Abstract  Chromium (Cr) is an essential mineral element that has received considerable public attention. The suggestion that Cr intake is generally low has generated interest regarding the purported beneficial effects of Cr supplementation on biological function and health of animals and humans. This review briefly describes key aspects of Cr nutritional status and evaluates the effects of Cr supplementation on various components of biological function, body composition, and health. A novel biological role of Cr in regulation of insulin function is described. Although promising results of Cr supplementation are presented, the considerable challenge of developing methods for routine assessment of Cr nutriture in humans remains.
METABOLIC ENGINEERING WITH RECOMBINANT ADENOVIRUSES
Authors: Antinozzi Peter A. , Berman Hal K. , O'Doherty Robert M. , Newgard Christopher B.
Published: July 2002

▪ Abstract  Fuel homeostasis in mammals is accomplished by the interplay between tissues and organs with distinct metabolic roles. These regulatory mechanisms are disrupted in obesity and diabetes, leading to a renewed emphasis on discovery of molecular and pharmacologic methods for reversing metabolic disorders. In this chapter, we review the use of recombinant adenoviral vectors as tools for delivering metabolic regulatory genes to cells in culture and to tissues of intact animals. Included are studies on the use of these vectors for gaining insights into the biochemical mechanisms that regulate glucose-stimulated insulin secretion from pancreatic islet β-cells. We also highlight their use for understanding the function of newly discovered genes that regulate glycogen metabolism in liver and other tissues, and for evaluating “candidate” genes such as glucose-6-phosphatase, which may contribute to development of metabolic dysfunction in pancreatic islets and liver. Finally, we discuss the use of adenoviral and related vectors for causing chronic increases in the levels of circulating hormones. These examples serve to highlight the power of viral gene transfer vectors as tools for understanding metabolic regulatory mechanisms.
The Role of the Microsomal Triglygeride Transfer Protein in Abetalipoproteinemia
Authors: Berriot-Varoqueaux N. , Aggerbeck L. P. , Samson-Bouma M.-E. , Wetterau J. R.
Published: July 2002

The microsomal triglyceride transfer protein (MTP) is a dimeric lipid transfer protein consisting of protein disulfide isomerase and a unique 97-kDa subunit. In vitro, MTP accelerates the transport of triglyceride, cholesteryl ester, and phospholipid between membranes. It was recently demonstrated that abetalipoproteinemia, a hereditary disease characterized as an inability to produce chylomicrons and very low-density lipoproteins in the intestine and liver, respectively, results from mutations in the gene encoding the 97-kDa subunit of the microsomal triglyceride transfer protein. Downstream effects resulting from this defect include malnutrition, very low plasma cholesterol and triglyceride levels, altered lipid and protein compositions of membranes and lipoprotein particles, and vitamin deficiencies. Unless treated, abetalipoproteinemic subjects develop gastrointestinal, neurological, ophthalmological, and hematological abnormalities.
EXPERIMENTAL STUDIES OF RESONANCES IN UNIMOLECULAR DECOMPOSITION
Authors: Reid Scott A. , Reisler Hanna
Published: July 2002

▪ Abstract  In recent years we have witnessed tremendous progress in our understanding of unimolecular reactions on a fully state-resolved level. Here we describe recent state-resolved experimental studies of resonances in unimolecular reactions, focusing on the transition from isolated to overlapping resonances. Depending on the well depth and extent of intramolecular vibrational energy redistribution, the resonances can exhibit properties ranging from mode- and state-selective to statistical behavior. In the statistical limit the resonances are usually overlapped, and interference effects may become prominent. We use recent studies of HCO, HFCO, and CH3O to examine the transition from mode-selective to statistical behavior in the isolated regime. Experimental and theoretical studies of NO2, including photofragment yield spectra, fully resolved NO quantum state distributions, and decomposition rates are used to examine unimolecular decomposition in the regime of overlapping resonances.
COHERENTNONLINEARSPECTROSCOPY: From Femtosecond Dynamics to Control
Authors: Dantus Marcos
Published: July 2002

▪ Abstract  This review focuses on the study of the dynamics of isolated molecules and their control using coherent nonlinear spectroscopic methods. Emphasis is placed on topics such as bound-to-free excitation and the study of concerted elimination reactions, free-to-bound excitation and the study of bimolecular reactions, and bound-to-bound excitation and the study of intramolecular rovibrational dynamics and coherence relaxation. For each case the detailed time-resolved information reveals possible strategies to control the outcome. Experimental results are shown for each of the reactions discussed. The methods discussed include pump-probe and four-wave mixing processes such as transient grating and photon echo spectroscopy. Off-resonance transient-grating experiments are shown to be ideal for the study of ground state dynamics, molecular structure, and the molecular response to strong field excitation.
PROTEOLYTIC ACTIVITIES THAT MEDIATE APOPTOSIS
Authors: Kidd Vincent J.
Published: July 2002

▪ Abstract  Since the discovery that cells can activate their own suicide program, investigators have attempted to determine whether the events that are associated with this form of cell death are genetically determined. The discovery that the ced-3 gene of Caenorhabditis elegans encodes a cysteine protease essential for developmentally regulated apoptosis ignited interest in this area of research. As a result, we now know that cell death is specified by a number of genes and that this biologic process contributes significantly to development, tumorigenesis, and autoimmune disease. In this review I summarize what is currently known about signaling pathways involved in apoptosis, with particular emphasis on the function of the cysteine proteases known as caspases. However, there is also evidence that protease-independent cell death pathways exist. Is there a relationship between these two distinct mechanisms? If so, how do they communicate? Finally, even though the involvement of tumor necrosis factor/nerve growth factor family of receptors and cysteine proteases has been elegantly established as a component of many apoptotic signaling pathways, what happens downstream of these initial events? Why are only a selected group of cellular proteins—many nuclear—the targets of these proteases? Are nuclear events essential for apoptosis in vivo? Are the cellular genes that encode products involved in apoptotic signaling frequent targets of mutation/alteration during tumorigenesis? These are only a few questions that may be answered in the next ten years.
FUNCTIONAL PROPERTIES AND PHYSIOLOGICAL ROLES OF ORGANIC SOLUTE CHANNELS
Authors: Kirk Kiaran , Strange Kevin
Published: July 2002

▪ Abstract  Membrane channels provide routes for the rapid, passive movement of solutes across plasma and intracellular membranes. It is generally assumed that the major physiological role of membrane channels is to transport inorganic ions for processes such as transepithelial salt absorption and secretion, cell volume regulation, signal transduction, and control of membrane electrical properties. Increasing evidence indicates, however, that channels play an important role in organic solute transport in a wide variety of cell types and organisms. Some of the major physiological roles of organic solute channels include uptake of nutrients, excretion of metabolic waste products, volume-regulatory organic osmolyte transport, and control of mitochondrial metabolism. This article reviews the functions and characteristics of channels that participate in the transport and regulation of both charged and electroneutral organic solutes.
MECHANISMS OF HAIR CELL TUNING
Authors: Fettiplace R. , Fuchs P. A.
Published: July 2002

▪ Abstract  Mechanosensory hair cells of the vertebrate inner ear contribute to acoustic tuning through feedback processes involving voltage-gated channels in the basolateral membrane and mechanotransduction channels in the apical hair bundle. The specific number and kinetics of calcium-activated (BK) potassium channels determine the resonant frequency of electrically tuned hair cells. Kinetic variation among BK channels may arise through alternative splicing of slo gene mRNA and combination with modulatory β subunits. The number of transduction channels and their rate of adaptation rise with hair cell response frequency along the cochlea's tonotopic axis. Calcium-dependent feedback onto transduction channels may underlie active hair bundle mechanics. The relative contributions of electrical and mechanical feedback to active tuning of hair cells may vary as a function of sound frequency.
Control of Growth by the Somatropic Axis: Growth Hormone and the Insulin-Like Growth Factors Have Related and Independent Roles
Authors: Butler Andrew A. , Roith Derek Le
Published: July 2002

▪ Abstract  The traditionally accepted theory has been that most of the biological effects of growth hormone (GH) are mediated by circulating (endocrine) insulin-like growth factor-I (IGF-I). This dogma was modified when it was discovered that most tissues express IGF-I that can act via an autocrine/paracrine fashion. In addition, both GH and IGF-I had independent effects on various target tissues. Using tissue-specific gene deletion of IGF-I in the liver, it has been shown that circulating IGF-I is predominantly liver-derived but is not essential for normal postnatal growth. Therefore, it is proposed that non-hepatic tissue-derived IGF-I may be sufficient for growth and development. Thus the original somatomedin hypothesis has undergone further modifications.
Nephrogenic Diabetes Insipidus
Authors: Morello Jean-Pierre , Bichet Daniel G
Published: July 2002

▪ Abstract  Nephrogenic diabetes insipidus, which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone arginine vasopressin. Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital nephrogenic diabetes insipidus are males with the X-linked recessive form of the disease (OMIM 304800) who have mutations in the arginine vasopressin receptor 2 gene (AVPR2), which codes for the vasopressin V2 receptor. The gene is located in chromosomal region Xq28. In <10% of the families studied, congenital nephrogenic diabetes insipidus has an autosomal-recessive or autosomal-dominant (OMIM 222000 and 125800, respectively) mode of inheritance. Mutations have been identified in the aquaporin-2 gene (AQP2), which is located in chromosome region 12q13 and codes for the vasopressin-sensitive water channel. When studied in vitro, most AVPR2 mutations result in receptors that are trapped intracellularly and are unable to reach the plasma membrane. A few mutant receptors reach the cell surface but are unable to bind arginine vasopressin or to properly trigger an intracellular cyclic AMP signal. Similarly, aquaporin-2 mutant proteins are misrouted and cannot be expressed at the luminal membrane. Chemical or pharmacological chaperones have been found to reverse the intracellular retention of aquaporin-2 and arginine vasopressin receptor 2 mutant proteins. Because many hereditary diseases stem from the intracellular retention of otherwise functional proteins, this mechanism may offer a new therapeutic approach to the treatment of those diseases that result from errors in protein kinesis.
Mechanisms of Iron Accumulation in Hereditary Hemochromatosis
Authors: Fleming Robert E. , Sly William S.
Published: July 2002

▪ Abstract  Hereditary hemochromatosis (HH) is a common inborn error of iron metabolism characterized by excess dietary iron absorption and iron deposition in several tissues. Clinical consequences include hepatic failure, hepatocellular carcinoma, diabetes, cardiac failure, impotence, and arthritis. Despite the discovery of the mutation underlying most cases of HH, considerable uncertainty exists in the mechanism by which the normal gene product, HFE, regulates iron homeostasis. Knockout of the HFE gene clearly confers the HH phenotype on mice. However, studies on HFE expressed in cultured cells have not yet clarified the mechanism by which HFE mutations lead to increased dietary iron absorption. Recent discoveries suggest other genes, including a second transferrin receptor and the circulating peptide hepcidin, participate in a shared pathway with HFE in regulation of iron absorption. This review summarizes our current understanding of the relationship between iron stores and absorption and presents models to explain the dysregulated iron homeostasis in HH.
THEMULTIFUNCTIONALCAPSIDPROTEINS OFPLANTRNA VIRUSES
Authors: Callaway A. , Giesman-Cookmeyer D. , Gillock E. T. , Sit T. L. , Lommel S. A.
Published: July 2002

▪ Abstract  This article summarizes studies of viral coat (capsid) proteins (CPs) of RNA plant viruses. In addition, we discuss and seek to interpret the knowledge accumulated to date. CPs are named for their primary function; to encapsidate viral genomic nucleic acids. However, encapsidation is only one feature of an extremely diverse array of structural, functional, and ecological roles played during viral infection and spread. Herein, we consider the evolution of viral CPs and their multitude of interactions with factors encoded by the virus, host plant, or viral vector (biological transmission agent) that influence the infection and epidemiological facets of plant disease. In addition, applications of today's understanding of CPs in the protection of crops from viral infection and use in the manufacture of valuable compounds are considered.
UNEXPLAINED INCREASES IN CANCER INCIDENCE IN THE UNITED STATES FROM 1975 TO 1994: Possible Sentinel Health Indicators?
Authors: Dinse Gregg E. , Umbach David M. , Sasco Annie J. , Hoel David G. , Davis Devra L.
Published: July 2002

▪ Abstract  To search for unexplained patterns in cancer incidence, we analyzed data from 1975 to 1994 that represent ∼10% of the population of the United States. Our analysis focused on long-term time trends in incidence and on deviations from those trends attributable to birth cohorts or to calendar periods. On average, cancer incidence rose 0.8% annually in white women and 1.8% in white men. After removing several cancers related to smoking and increased screening, average annual increases fell to 0.1% in white women but persisted at 1.7% in white men. In particular, yearly increases in non-Hodgkin's lymphoma averaged 2.4% in white women and 4.7% in white men. Among men, incidence changes attributable to cohorts grew progressively larger from one cohort to the next. Cancer incidence patterns among black men and women were similar to those among whites despite smaller population sizes. Unexplained patterns of cancer incidence may signal changes in underlying risk factors and highlight the continuing need for research on cancer etiology and prevention.
The Case for a Medicare Drug Coverage Benefit: A Critical Review of the Empirical Evidence
Authors: Adams Alyce S , Soumerai Stephen B , Ross-Degnan Dennis
Published: July 2002

▪ Abstract  The lack of an outpatient prescription drug benefit under Medicare has become a conspicuous omission in the face of accelerated growth in prescription drug expenditures and increased availability of highly effective medications. This article provides a critical review of the empirical evidence on the effect of drug coverage on the use of prescription drugs, health care outcomes, and health care costs among Medicare beneficiaries. The existing literature provides considerable evidence that drug coverage is associated with greater use of all drugs and clinically essential medications and that not all forms of coverage provide the same protection. Longitudinal evidence from elderly and disabled persons in Medicaid indicates that restricting coverage has serious adverse health outcomes for sick and low-income beneficiaries that actually lead to increased health care costs.
Myosin Light Chain Phosphorylation in Neutrophil-Stimulated Coronary Microvascular Leakage
Authors: Yuan Sarah Y. , Wu Mack H. , Ustinova Elena E. , Guo Mingzhang , Tinsley John H. , de Lanerolle Primal , Xu Wenjuan
Published: July 2002

Neutrophil-induced coronary microvascular leakage represents an important pathophysiological consequence of ischemic and inflammatory heart diseases. The precise mechanism by which neutrophils regulate endothelial barrier function remains to be established. The aim of this study was to examine the microvascular endothelial response to neutrophil activation with a focus on myosin light chain kinase (MLCK)-mediated myosin light chain (MLC) phosphorylation, a regulatory process that controls cell contraction. The apparent permeability coefficient of albumin (Pa) was measured in intact isolated porcine coronary venules. Incubation of the vessels with C5a-activated neutrophils induced a time- and concentration-dependent increase in Pa. The hyperpermeability response was significantly attenuated during inhibition of endothelial MLC phosphorylation with the selective MLCK inhibitor ML-7 and transfection of a specific MLCK-inhibiting peptide. In contrast, transfection of constitutively active MLCK elevated Pa, which was abolished by ML-7. In addition to the vessel study, albumin transendothelial flux was measured in cultured bovine coronary venular endothelial monolayers, which displayed a hyperpermeability response to neutrophils and MLCK in a pattern similar to that in venules. Importantly, neutrophil stimulation caused MLC phosphorylation in endothelial cells in a time course closely correlated with that of the hyperpermeability response. Consistently, the MLCK inhibitors abolished neutrophil-induced MLC phosphorylation. Furthermore, immunohistochemical observation of neutrophil-stimulated endothelial cells revealed an increased staining for phosphorylated MLC in association with contractile stress fiber formation and intercellular gap development. Taken together, the results suggest that endothelial MLCK activation and MLC phosphorylation play an important role in mediating endothelial barrier dysfunction during neutrophil activation.
Most-Favored-Nation Clauses and Clustered Negotiations
Authors: Pahre Robert
Published: July 2002

Though substantively important, centralized negotiations have received less theoretical attention than problems of centralized monitoring and enforcement. I address this gap by examining variation in a particular form of centralized negotiations that I call “clustering.” Clustering occurs when a state negotiates with several other states at the same time. Clustering enables states to avoid having to make concessions on the same issue to one state after another, and therefore has important distributional advantages. Clustering also centralizes bargaining within a regime, especially when several states cluster simultaneously in a “macro-cluster.”

I propose several hypotheses about clustering. First, most-favored-nation (MFN) clauses are a necessary condition for clustering. They link the distributional conflicts among many pairs of countries and make centralized bargaining more likely. Second, increasing membership in the trade regime makes clustering more likely. This relationship between membership and centralization echoes Rational Design conjecture C3, centralization increases with number, though the causal mechanism differs significantly. Third, clustering provides distributional advantages to those who cluster. A state that clusters, such as France under the Méline tariff or Germany under Chancellors Leo von Caprivi and Bernard von Bülow, will make fewer concessions than one that does not.
The Pathway Between Art and Science: One Painter's Metaphorical Journey
Authors: Levrier Guy
Published: July 2002

The author describes his un-derstanding of the place and pur-pose of his art in the context of our late twentieth century: as an artist, he does not accept a place in the current “death of art” situa-tion. He agrees that abstract art is not self-explanatory although its meaning exists in the collective unconscious. To explain his effort, he has found metaphors in quan-tum physics that enable him to link his artistic process to the dy-namics of progress found in sci-ence rather than to those of re-gression found in the arts.
The Art of Creating Subjective Reality: An Analysis of Japanese Digital Pets
Authors: Kusahara Machiko
Published: July 2002

A variety of digital pets can be found in Japan, from virtual pets on palm-top game screens to physical entertainment robots. They are successful because they succeed in promoting a sense of reality in users' minds. While visual reality is a familiar element of realism, a subjective sense of reality can also prove effective. By designing interaction in a mode that takes users' psychology into account, such a sense of reality can be enhanced, especially when a user perceives an independent personality in his/her digital pet. Japanese traditional culture, which allows treating animals on an equal basis with human beings, is behind this psychology.
From the Back of the Eyelids: Public and Private Space in an Interactive Installation
Authors: Conlon Juliet
Published: July 2002

The author describes how her recent installation work combines video, velvet, and interactivity into an opportunity for intimate navigation over the skin of a composite body. She discusses how the installation engages the senses using touchscreens, virtual projectors, and the human form to contrast private space with public space.
Order in Phrase Structure and Movement
Authors: Saito Mamoru , Fukui Naoki
Published: July 2002

This article proposes the following mechanism of Merge, modifying and incorporating the effect of the head parameter:

K = {γ, 〈α, β〉}, where γ ε {α, β} a. γ = α: head-initial, left-headed b. γ = β: head-final, right-headed

It is argued that under the parameterized version of Merge, traditional “adjunction” operations (scrambling and heavy NP shift) are characterized as substitution in the sense that they always accompany the projection of the target, whereas traditional “substitution” operations (wh-movement and NP-movement) are analyzed as genuine adjunction. It is then shown that numerous empirical consequences follow from this theory of phrase structure and movement, including (a) the nature and distribution of optional movements, (b) an elegant account of some peculiar properties of specifiers, and (c) a new unification of adjunct and subject condition effects, with a natural explanation of the parametric variation associated with the latter effect.
Neuromagnetic Correlates of Sensorimotor Synchronization
Authors: Müller Katharina , Schmitz Frank , Schnitzler Alfons , Freund Hans-Joachim , Aschersleben Gisa , Prinz Wolfgang
Published: July 2002

Sensorimotor synchronization tasks, in which subjects have to tap their finger in synchrony with an isochronous auditory click, typically reveal a synchronization error with the tap preceding the click by about 20 to 50 msec. Although extensive behavioral studies and a number of different explanatory accounts have located the cause of this so-called “negative asynchrony” on different levels of processing, the underlying mechanisms are still not completely understood. Almost nothing is known about the central processes, in particular, which sensory or motor events are synchronized by subjects. The present study examined central-level processing in synchronization tasks with magnetoencephalography (MEG). Eight subjects synchronized taps with their right index finger to an isochronous binaural pacing signal presented at an interstimulus interval of 800 msec. To gain information on central temporal coupling between “tap” and “click”, evoked responses were averaged time-locked to the auditory signal and the tap onset. Tap-related responses could be explained with a three dipole model: One source, peaking at approximately 77 msec before tap onset, was localized in contralateral primary motor cortex (MI); the two other sources, peaking approximately at tap onset and 75 msec after tap onset, in contralateral primary somatosensory cortex (SI). Temporal coupling of these sources was compared in relation to different trigger points. The second SI source was equally well time-locked to the tap and to the auditory click. Furthermore, analysis of the time locking of this source activity as a function of the temporal order of tap and click showed that the second event—irrespective whether tap or click—was decisive in triggering the second SI source. This suggests that subjects use mainly sensory feedback in judging and evaluating whether they are “keeping time.”
Amnesia and the Declarative/Nondeclarative Distinction: A Recurrent Network Model of Classification, Recognition, and Repetition Priming
Authors: Kinder Annette , Shanks David R.
Published: July 2002

A key claim of current theoretical analyses of the memory impairments associated with amnesia is that certain distinct forms of learning and memory are spared. Supporting this claim, B. J. Knowlton and L R. Squire found that amnesic patients and controls were indistinguishable in their ability to learn about and classify strings of letters generated from a finite-state grammar, but that the amnesics were impaired at recognizing the training strings. We show, first, that this pattern of results is predicted by a single-system connectionist model of artificial grammar learning (AGL) in which amnesia is simulated by a reduced learning rate. We then show in two experiments that a counterintuitive assumption of this model, that classification and recognition are functionally identical in AGL, is correct. In three further simulation studies, we demonstrate that the model also reproduces another type of dissociation, namely between recognition memory and repetition priming. We conclude that the performance of amnesic patients in memory tasks is better understood in terms of a nonselective, rather than a selective, memory deficit.
Separating Storage from Retrieval Dysfunction of Temporal Memory in Parkinson's Disease
Authors: Malapani Chara , Deweer Bernard , Gibbon John
Published: July 2002

Dysfunction of the basal ganglia and the brain nuclei interconnected with them leads to disturbances of movement and cognition exemplified in Parkinson's disease (PD) and Huntington's disease, including disordered timing of movements and impaired time estimation. Previous research has shown that whereas striatal damage in animals can result in the loss of temporal control over behavior, dopaminergic deregulation in the human striatum associated with PD distorts the memory for time. Here we show a dissociation between deficits in storage (writing to) and retrieval (reading from) temporal memory processes. Both are dysfunctional in PD and sensitive to treatment with dopaminergic agents, but produce dissimilar distortions. When time intervals are stored in memory while the subjects are dopamine depleted, the process is slowed, leading to overestimation of two different time intervals. Conversely, when retrieval occurs in a dopamine-depleted state, interference or coupling occurs between two remembered time intervals, producing overestimation of the shorter and underestimation of the longer one. Whether those two separable patterns of dysfunction in storing and retrieving temporal memories rely on distinct neural networks within the basal ganglia and/or their cortical targets remains to be answered by future research.