bluuebunny/crossref_metadata_2025 huggingface dataset:
Algorithm 673
Authors: Vitter Jeffrey Scott
Published: July 2002

We present a Pascal implementation of the one-pass algorithm for constructing dynamic Huffman codes that is described and analyzed in a companion paper. The program runs in real time; that is, the processing time for each letter of the message is proportional to the length of its codeword. The number of bits used to encode a message of
t
letters is less than
t
bits more than that used by the well-known two-pass algorithm. This is best possible for any one-pass Huffman scheme. In practice, it uses fewer bits than all other Huffman schemes. The algorithm has applications in file compression and network transmission.
SOME RECENT TRENDS IN GRAMMATICALIZATION
Authors: Hopper Paul J.
Published: July 2002

▪ Abstract  Grammaticalization—the transformation of lexical items and phrases into grammatical forms—has been the focus of considerable study. Two chief directions can be identified. The first involves etymology and the taxonomy of possible changes in language, in which semantic and cognitive accounts of words and categories of words are considered to explain the changes. The second involves the discourse contexts within which grammaticalization occurs. Some researchers have questioned the standard idea of a stable synchronic a priori grammar in which linguistic structure is distinct from discourse, and have sought to replace this with the idea of “emergent grammar” in which repetitions of various kinds in discourse lead to perpetual structuration.
Antievolution and Creationism in the United States
Authors: Scott Eugenie C.
Published: July 2002

Evolution is considered controversial by a substantial minority of Americans. Religious opposition explains this, but this opposition is comprised of a broad continuum of religious views. It runs from “young earth creationism” through “old earth creationism” (including “day-age,” “gap,” and “progressive creationism”) to “theistic evolutionism.” Historically, antievolutionists have attempted to ban evolution and to present it on an equal footing with “creation science.” Scholars largely ignored antievolutionism until efforts to pass “equal time for creation and evolution” laws stimulated both political and scholarly activism. Lately, there are efforts to discourage the teaching of evolution by requiring teachers to read disclaimers before teaching it, to teach it as “theory, not fact,” or to present fancied “evidence against evolution.” Recently, “intelligent design theory,” a restatement of William Paley's Argument from Design, has surfaced. Although rejected by scientists, intelligent design arguments and publications are appearing at the college level (in nonscience courses) as accurate representations of scientific scholarship.
The Biology and Evolution of HIV
Authors: Hutchinson Janis Faye
Published: July 2002

▪ Abstract  This review examines the current state of knowledge about HIV/AIDS in terms of its origins, pathogenesis, genetic variation, and evolutionary biology. The HIV virus damages the host's immune system, resulting in AIDS, which is characterized by immunodeficiency, opportunistic infections, neoplasms, and neurological problems. HIV is a complex retrovirus with a high mutation rate. This mutation rate allows the virus to evade host immune responses, and evidence indicates that selection favors more virulent strains with rapid replication. While a number of controversial theories attempt to explain the origin of HIV/AIDS, phylogenetic evidence suggests a zoonotic transmission of HIV to humans and implicates the chimpanzee (Pan troglodytes troglodytes) as the source of HIV-1 infection and the sooty mangabey as the source of HIV-2 infection in human populations. New therapies provide hope for increased longevity among people living with AIDS, but the biology of HIV presents significant obstacles to finding a cure and/or vaccine. HIV continues to be a threat to the global population because of its fast mutation rate, recombinogenic effect, and its use of human defenses to replicate itself.
ENDOSPERM DEVELOPMENT: Cellularization and Cell Fate Specification
Authors: Olsen Odd-Arne
Published: July 2002

▪ Abstract  The endosperm develops from the central cell of the megagametophyte after introduction of the second male gamete into the diploid central cell. Of the three forms of endosperm in angiosperms, the nuclear type is prevalent in economically important species, including the cereals. Landmarks in nuclear endosperm development are the coenocytic, cellularization, differentiation, and maturation stages. The differentiated endosperm contains four major cell types: starchy endosperm, aleurone, transfer cells, and the cells of the embryo surrounding region. Recent research has demonstrated that the first two phases of endosperm occur via mechanisms that are conserved among all groups of angiosperms, involving directed nuclear migration during the coenocytic stage and anticlinal cell wall deposition by cytoplasmic phragmoplasts formed in interzones between radial microtubular systems emanating from nuclear membranes. Complete cellularization of the endosperm coenocyte is achieved through centripetal growth of cell files, extending to the center of the endosperm cavity. Key points in cell cycle control and control of the MT (microtubular) cytoskeletal apparatus central to endosperm development are discussed. Specification of cell fates in the cereal endosperm appears to occur via positional signaling; cells in peripheral positions, except over the main vascular tissues, assume aleurone cell fate. Cells over the main vascular tissue become transfer cells and all interior cells become starchy endosperm cells. Studies in maize have implicated Crinkly4, a protein receptor kinase-like molecule, in aleurone cell fate specification.
MECHANISTICFEATURES OF THEMO-CONTAININGNITROGENASE
Authors: Christiansen Jason , Dean Dennis R , Seefeldt Lance C
Published: July 2002

▪ Abstract  Nitrogenase is the complex metalloenzyme responsible for biological dinitrogen reduction. This reaction represents the single largest contributor to the reductive portion of the global nitrogen cycle. Recent developments in understanding the mechanism of the Mo-based nitrogenase are reviewed. Topics include how nucleotide binding and hydrolysis are coupled to electron transfer and substrate reduction, how electrons are accumulated and transferred within the MoFe-protein, and how substrates bind and are reduced at the active site metal cluster.
DENSE PHOTODISSOCIATION REGIONS (PDRs)
Authors: Hollenbach D. J. , Tielens A. G. G. M.
Published: July 2002

▪ Abstract  All neutral atomic hydrogen gas and a large fraction of the molecular gas in the Milky Way Galaxy and external galaxies lie in PDRs, and PDRs are the origin of most of the nonstellar infrared (IR) and the millimeter CO emission from a galaxy. On the surfaces (Av< 1−3) of interstellar clouds, the absorption of far ultraviolet (FUV) photons (hν < 13.6 eV) by gas and dust grains leads to intense emission of [C II] 158 μm, [O I] 63, 146 μm, and H2rovibrational transitions, as well as IR dust continuum and polycyclic aromatic hydrocarbon (PAH) emission features. Deeper in PDRs, CO rotational and [C I] 370, 609 μm lines originate. The transition of H to H2and C+to CO occurs within PDRs. Theoretical models compared with observations diagnose such physical parameters as the density and temperature structure, the elemental abundances, and the FUV radiation field in PDRs. Applications include clouds next to H II regions, reflection nebulae, planetary nebulae, red giant outflows, circumstellar gas around young stars, diffuse clouds, the warm neutral medium (WNM), and molecular clouds in the interstellar radiation field: in summary, much of the interstellar medium in galaxies. This review focuses on dense PDRs in the Milky Way Galaxy. Theoretical PDR models help explain the observed correlation of the CO J = 1–0 luminosity with the molecular mass and also suggest FUV-induced feedback mechanisms that may regulate star formation rates and the column density through giant molecular clouds.
THE LYMAN ALPHA FOREST IN THE SPECTRA OF QUASISTELLAR OBJECTS
Authors: Rauch Michael
Published: July 2002

▪ Abstract  Observations of redshifted Lyman α (Lyα) forest absorption in the spectra of quasistellar objects (QSOs) provide a highly sensitive probe of the distribution of gaseous matter in the universe. Over the past two decades, optical spectroscopy with large ground-based telescopes, and more recently ultraviolet (UV) spectroscopy from space, have yielded a wealth of information on what appears to be a gaseous, photoionized intergalactic medium (IGM), partly enriched by the products of stellar nucleosynthesis, residing in coherent structures over many hundreds of kiloparsecs.

Recent progress with cosmological hydro-simulations based on hierarchical structure formation models has led to important insights into the physical structures giving rise to the forest. If these ideas are correct, a truly inter- and protogalactic medium [at high redshift (z ∼ 3), the main repository of baryons] collapses under the influence of dark matter gravity into flattened or filamentary structures, which are seen in absorption against background QSOs. With decreasing redshift, galaxies forming in the denser regions may contribute an increasing part of the Lyα absorption cross section. Comparisons between large data samples from the new generation of telescopes and artificial Lyα forest spectra from cosmological simulations promise to become a useful cosmological tool.
X-Ray Properties of Groups of Galaxies
Authors: Mulchaey John S.
Published: July 2002

▪ Abstract  ROSAT observations indicate that approximately half of all nearby groups of galaxies contain spatially extended X-ray emission. The radial extent of the X-ray emission is typically 50–500 h−1100 kpc or approximately 10–50% of the virial radius of the group. Diffuse X-ray emission is generally restricted to groups that contain at least one early-type galaxy. X-ray spectroscopy suggests the emission mechanism is most likely a combination of thermal bremsstrahlung and line emission. This interpretation requires that the entire volume of groups be filled with a hot, low-density gas known as the intragroup medium. ROSAT and ASCA observations indicate that the temperature of the diffuse gas in groups ranges from approximately 0.3 keV to 2 keV. Higher temperature groups tend to follow the correlations found for rich clusters between X-ray luminosity, temperature, and velocity dispersion. However, groups with temperatures below approximately 1 keV appear to fall off the cluster LX-T relationship (and possibly the LX-σ and σ-T cluster relationships, although evidence for these latter departures is at the present time not very strong). Deviations from the cluster LX-T relationship are consistent with preheating of the intragroup medium by an early generation of stars and supernovae.

There is now considerable evidence that most X-ray groups are real, physical systems and not chance superpositions or large-scale filaments viewed edge-on. Assuming the intragroup gas is in hydrostatic equilibrium, X-ray observations can be used to estimate the masses of individual systems. ROSAT observations indicate that the typical mass of an X-ray group is ∼1013 h−1100 M[Formula: see text] out to the radius to which X-ray emission is currently detected. The observed baryonic masses of groups are a small fraction of the X-ray determined masses, which implies that groups are dominated by dark matter. On scales of the virial radius, the dominant baryonic component in groups is likely the intragroup medium.
Phenomenology of Broad Emission Lines in Active Galactic Nuclei
Authors: Sulentic J. W. , Marziani P. , Dultzin-Hacyan D.
Published: July 2002

▪ Abstract  Broad emission lines hold fundamental clues about the kinematics and structure of the central regions in AGN. In this article we review the most robust line profile properties and correlations emerging from the best data available. We identify fundamental differences between the profiles of radio-quiet and radio-loud sources as well as differences between the high- and low-ionization lines, especially in the radio-quiet majority of AGN. An Eigenvector 1 correlation space involving FWHM Hβ, W(FeIIopt)/W(Hβ), and the soft X-ray spectral index provides optimal discrimination between all principal AGN types (from narrow-line Seyfert 1 to radio galaxies). Both optical and radio continuum luminosities appear to be uncorrelated with the E1 parameters. We identify two populations of radio-quiet AGN: Population A sources (with FWHM(Hβ) [Formula: see text] 4000 km s−1, generally strong FeII emission and a soft X-ray excess) show almost no parameter space overlap with radio-loud sources. Population B shows optical properties largely indistinguishable from radio-loud sources, including usually weak FeII emission, FWHM(Hβ) [Formula: see text] 4000 km s−1and lack of a soft X-ray excess. There is growing evidence that a fundamental parameter underlying Eigenvector 1 may be the luminosity-to-mass ratio of the active nucleus (L/M), with source orientation playing a concomitant role.
The Orion Nebula and Its Associated Population
Authors: O'Dell C. R.
Published: July 2002

▪ Abstract  The Orion Nebula (M 42) is one of the best studied objects in the sky. The advent of multi-wavelength investigations and quantitative high resolution imaging has produced a rapid improvement in our knowledge of what is widely considered the prototype H II region and young galactic cluster. Perhaps uniquely among this class of object, we have a good three dimensional picture of the nebula, which is a thin blister of ionized gas on the front of a giant molecular cloud, and the extremely dense associated cluster. The same processes that produce the nebula also render visible the circumstellar material surrounding many of the pre–main sequence low mass stars, while other circumstellar clouds are seen in silhouette against the nebula. The process of photoevaporation of ionized gas not only determines the structure of the nebula that we see, but is also destroying the circumstellar clouds, presenting a fundamental conundrum about why these clouds still exist.
GENETICS OF TRANSCRIPTIONAL REGULATION IN YEAST: Connections to the RNA Polymerase II CTD
Authors: Carlson Marian
Published: July 2002

▪ Abstract  Transcriptional regulation is important in all eukaryotic organisms for cell growth, development, and responses to environmental change. Saccharomyces cerevisiae, or bakers' yeast, has provided a powerful system for genetic analysis of transcriptional regulation, and findings from the study of this model system have proven broadly applicable to higher organisms. Transcriptional regulation requires the interactions of regulatory proteins with various components of the transcription machinery. Recently, genetic analysis of a diverse set of transcriptional regulatory responses has converged with studies of the function of the RNA polymerase II carboxy-terminal domain (CTD) to reveal regulatory roles for proteins associated with the CTD. These proteins, designated Srb/mediator proteins, are broadly involved in both positive and negative regulatory responses in vivo. This review focuses on the connections between genetic analysis of transcriptional regulation and the functions of the Srb/mediator proteins associated with the RNA polymerase II CTD.
DETERMINATION OF THE COMPOSITION AND STATE OF ICY SURFACES IN THE OUTER SOLAR SYSTEM
Authors: Brown Robert H. , Cruikshank Dale P.
Published: July 2002

▪ Abstract  Telescopic data combined with data gathered by spacecraft has brought worlds as distant as Pluto and the Kuiper belt objects under increasingly close scrutiny. Of particular interest here is the progress that has been made in our understanding of the properties of the satellites of the giant planets. As such, the purpose of this chapter is to review the present understanding of the nature of icy surfaces in the outer solar system, the ongoing processes that affect the composition, distribution, and physical state of volatiles on icy surfaces, and new techniques for probing the mysteries of the origin and evolution of icy bodies in the Solar System.
MARS 2000
Authors: Albee Arden L.
Published: July 2002

Twenty years after the Viking Mission, Mars is again being scrutinized in the light of a flood of information from spacecraft missions to Mars, the Hubble Space Telescope, and the SNC meteorites. This review provides an overview of the current understanding of Mars, especially in light of the data being returned from the Mars Global Surveyor Mission. Mars does not now have a global magnetic field, but the presence of crustal anomalies indicates that a global field existed early in Martian history. The topography, geodetic figure, and gravitational field are known to high precision. The northern hemisphere is lower and has a thinner and stronger crust than the southern hemisphere.

The global weather and the thermal structure of the atmosphere have been monitored for more than a year. Surface-atmosphere interaction has been investigated by observations of surface features, polar caps, atmospheric dust, and condensate clouds. The surface has been imaged at very high resolution and spectral measures have been obtained to quantify surface characteristics and geologic processes. Many questions remain unanswered, especially about the earliest period of Mars’ history.
Scaling, Universality, and Geomorphology
Authors: Dodds Peter Sheridan , Rothman Daniel H.
Published: July 2002

Theories of scaling apply wherever similarity exists across many scales. This similarity may be found in geometry and in dynamical processes. Universality arises when the qualitative character of a system is sufficient to quantitatively predict its essential features, such as the exponents that characterize scaling laws. Within geomorphology, two areas where the concepts of scaling and universality have found application are the geometry of river networks and the statistical structure of topography. We begin this review with a pedagogical presentation of scaling and universality. We then describe recent progress made in applying these ideas to networks and topography. This overview leads to a synthesis that attempts a classification of surface and network properties based on generic mechanisms and geometric constraints. We also briefly review how scaling and universality have been applied to related problems in sedimentology—specifically, the origin of stromatolites and the relation of the statistical properties of submarine-canyon topography to the size distribution of turbidite deposits. Throughout the review, our intention is to elucidate not only the problems that can be solved using these concepts, but also those that cannot.
Volcanoes, Fluids, and Life at Mid-Ocean Ridge Spreading Centers
Authors: Kelley Deborah S. , Baross John A. , Delaney John R.
Published: July 2002

▪ Abstract  The recent recognition of a potentially vast, unexplored hot microbial biosphere associated with active volcanism along the global mid-ocean ridge network has fundamentally shifted concepts of how planets and life coevolve. Many processes intrinsic to the dynamics of the spreading center volcanic system provide partial or complete nutritional fluxes that support diverse microbial communities that thrive under extreme conditions on and beneath the seafloor. Mantle melting, volcanism, and fluid-rock reactions transport volatiles from the asthenosphere to the hydrosphere. Volcanic heat and exothermic reactions drive circulation of nutrient-rich fluids from which chemosynthetic organisms gain metabolic energy. In turn, many of these organisms symbiotically support macrofaunal communities that populate the vents. Long-term seafloor observatories will allow exploration of linkages between volcanism and this newly discovered biosphere. Such approaches may provide essential new information about our own planet while providing critically needed insights into how we can explore other planets for life.
TROPICAL DEFORESTATION AND THE GLOBAL CARBON BUDGET
Authors: Melillo J. M. , Houghton R. A. , Kicklighter D. W. , McGuire A. D.
Published: July 2002

▪ Abstract  The CO2concentration of the atmosphere has increased by almost 30% since 1800. This increase is due largely to two factors: the combustion of fossil fuel and deforestation to create croplands and pastures. Deforestation results in a net flux of carbon to the atmosphere because forests contain 20–50 times more carbon per unit area than agricultural lands. In recent decades, the tropics have been the primary region of deforestation. The annual rate of CO2released due to tropical deforestation during the early 1990s has been estimated at between 1.2 and 2.3 gigatons C. The range represents uncertainties about both the rates of deforestation and the amounts of carbon stored in different types of tropical forests at the time of cutting. An evaluation of the role of tropical regions in the global carbon budget must include both the carbon flux to the atmosphere due to deforestation and carbon accumulation, if any, in intact forests. In the early 1990s, the release of CO2from tropical deforestation appears to have been mostly offset by CO2uptake occurring elsewhere in the tropics, according to an analysis of recent trends in the atmospheric concentrations of O2and N2. Interannual variations in climate and/or CO2fertilization may have been responsible for the CO2uptake in intact forests. These mechanisms are consistent with site-specific measurements of net carbon fluxes between tropical forests and the atmosphere, and with regional and global simulations using process-based biogeochemistry models.
RESISTANCE OF DROSOPHILA TO TOXINS
Authors: Wilson Thomas G.
Published: July 2002

▪ Abstract  Insects, including Drosophila, readily respond to toxins such as phytotoxins, metal ions, and insecticides in their environment by evolving resistance. Although Drosophila are seldom targets for insecticides, nevertheless populations worldwide have evolved resistance to a variety of insecticides, and these resistance alleles persist in high frequency. In many cases, Drosophila use the same genetic and biochemical mechanisms that underlie resistance in pest insects, including single-site changes in target molecules resulting from point mutations and upregulation of degradative enzymes, particularly cytochrome P450 enzymes and glutathione S-transferases. However, several types of resistance found in pest insects, such as gene amplification and knock-down resistance, have not been reported in Drosophila field populations. Excellent Drosophila-plant models are being studied to understand the adaptation to phytotoxins; P450 enzymes are clearly involved in phytotoxin resistance in one of these models. The genetic advantages of D. melanogaster, including availability of the sequenced genome, should allow further study of these genes and identification of new ones, particularly regulatory genes, responsible for resistance.
FLUID DYNAMICS OF El NIÑO VARIABILITY
Authors: Dijkstra Henk A. , Burgers Gerrit
Published: July 2002

▪ Abstract  The El Niño variability in the equatorial Tropical Pacific is characterized by sea-surface temperature anomalies and associated changes in the atmospheric circulation. Through an enormous monitoring effort over the last decades, the relevant time scales and spatial patterns are fairly well documented. In the meantime, a hierarchy of models has been developed to understand the physics of this phenomenon and to make predictions of future variability. In this review, the robust and relevant details of the observations, the fluid mechanical “building blocks,” the theory of the deterministic part of the variability, and the impact of small-scale (“noise”) and remote (“external”) processes are evaluated.
GENETICS OF PRIONS
Authors: Prusiner Stanley B. , Scott Michael R.
Published: July 2002

▪ Abstract  Prions are unprecedented infectious pathogens that cause a group of invariably fatal, neurodegenerative diseases by an entirely novel mechanism. Prion diseases may present as genetic, infectious, or sporadic disorders, all of which involve modification of the prion protein (PrP). The human prion disease Creutzfeldt-Jakob disease (CJD) generally presents as a progressive dementia, whereas scrapie of sheep and bovine spongiform encephalopathy (BSE) are manifest as ataxic illnesses. Prions are devoid of nucleic acid and seem to be composed exclusively of a modified isoform of PrP designated PrPSc. The normal, cellular PrP designated PrPCis converted into PrPScthrough a process whereby some of its α-helical structure is converted into β-sheet. The species of a particular prion is encoded by the sequence of the chromosomal PrP gene of the mammals in which it last replicated. In contrast to pathogens with a nucleic acid genome, prions encipher strain-specific properties in the tertiary structure of PrPSc. Transgenetic studies argue that PrPScacts as a template upon which PrPCis refolded into a nascent PrPScmolecule through a process facilitated by another protein.
EUREKA! AND OTHER PLEASURES
Authors: Metzger H.
Published: July 2002

At first one is very pleased at being invited to write a Prefatory Chapter, but as the delivery deadline draws closer one begins to think, “Oh my God! What on earth can I say that all but family members and few close friends will not find a great bore?” One solution is to write a scientific essay, but I concluded that that was a cop-out. I decided that perhaps the best tack to follow was to try to convey to the reader the personal characteristics I bring to my science and to other aspects of my professional career. The writing of this chapter has certainly convinced me that my particular background influenced what problems I chose to work on and how I approached their solution, but I hope that my results have a more ecumenical significance. There's been much written recently about how one's cultural background affects one's science, but I think that thesis can also be exaggerated. Science is a method of inquiry that by using certain guidelines permits rational individuals to observe Nature in a way that their findings will agree and have permanence. We shouldn't be diffident about defending that claim of objectivity.
Population Biology of Lymphocytes: The Flight for Survival
Authors: Freitas Antonio A. , Rocha Benedita
Published: July 2002

In this essay we suggest that the primary goal of the cells of the immune system is to ensure their own growth and survival. In adults, in steady-state conditions, the number and distribution of lymphocyte populations is under homeostatic control. New lymphocytes that are continuously produced in primary and secondary lymphoid organs must compete with resident cells for survival. We discuss recent findings supporting lymphocyte survival as a continuous active process and implicating cognate receptor engagement as fundamental survival signals for both T and B lymphocytes. The conflict of survival interests between different cell types gives rise to a pattern of interactions that mimics the behavior of complex ecological systems. In their flight for survival and in response to competition, lymphocytes use different survival signals within different ecological niches during cell differentiation. This is the case for T and B lymphocytes and also for naive and memory/activated T and B cells. We discuss how niche differentiation allows the co-existence of different cell types and guarantees both repertoire diversity and efficient immune responses.
Immunology of Tuberculosis
Authors: Flynn JoAnne L. , Chan John
Published: July 2002

The resurgence of tuberculosis worldwide has intensified research efforts directed at examining the host defense and pathogenic mechanisms operative in Mycobacterium tuberculosis infection. This review summarizes our current understanding of the host immune response, with emphasis on the roles of macrophages, T cells, and the cytokine/chemokine network in engendering protective immunity. Specifically, we summarize studies addressing the ability of the organism to survive within macrophages by controlling phagolysosome fusion. The recent studies on Toll-like receptors and the impact on the innate response to M. tuberculosis are discussed. We also focus on the induction, specificity, and effector functions of CD4+and CD8+T cells, and the roles of cytokines and chemokines in the induction and effector functions of the immune response. Presentation of mycobacterial antigens by MHC class I, class II, and CD1 as well as the implications of these molecules sampling various compartments of the cell for presentation to T cells are discussed. Increased attention to this disease and the integration of animal models and human studies have afforded us a greater understanding of tuberculosis and the steps necessary to combat this infection. The pace of this research must be maintained if we are to realize an effective vaccine in the next decades.
Molecular Genetics of Human Thyroid Neoplasms
Authors: Fagin James A.
Published: July 2002

Cancers are thought to develop as a result of sequential mutations of genes important in the control of cellular growth. Recently investigators identified a number of genetic defects that affect oncogenes and tumor-suppressor genes and that provide insight into the biology of benign and malignant thyroid neoplasms. Future implications for thyroid tumor diagnosis and prognosis are considered in this chapter.
ADVANCED PROTEIN GLYCOSYLATION IN DIABETES AND AGING
Authors: Brownlee, M.D Michael
Published: July 2002

▪ Abstract  Products of advanced protein glycosylation (advanced glycation end products, or AGEs) accumulate in tissues as a function of time and sugar concentration. AGEs induce permanent abnormalities in extracellular matrix component function, stimulate cytokine and reactive oxygen species production through AGE-specific receptors, and modify intracellular proteins. Pharmacologic inhibition of AGE formation in long-term diabetic animals prevents diabetic retinopathy, nephropathy, neuropathy, and arterial abnormalities in animal models. Clinical trials in humans are currently in progress.
Angiogenesis and Tumor Metastasis
Authors: Zetter Bruce R.
Published: July 2002

Angiogenesis, the recruitment of new blood vessels, is an essential component of the metastatic pathway. These vessels provide the principal route by which tumor cells exit the primary tumor site and enter the circulation. For many tumors, the vascular density can provide a prognostic indicator of metastatic potential, with the highly vascular primary tumors having a higher incidence of metastasis than poorly vascular tumors. Tumor angiogenesis is regulated by the production of angiogenic stimulators including members of the fibroblast growth factor and vascular endothelial growth factor families. In addition, tumors may activate angiogenic inhibitors such as angiostatin and endostatin that can modulate angiogenesis both at the primary site and at downstream sites of metastasis. The potential use of these and other natural and synthetic angiogenic inhibitors as anticancer drugs is currently under intense investigation. Such agents may have reduced toxicity and be less likely to generate drug resistance than conventional cytotoxic drugs. Clinical trials are now underway to develop optimum treatment strategies for antiangiogenic agents.
Dyspepsia: Current Understanding and Management
Authors: Agréus L. , Talley N. J.
Published: July 2002

Dyspepsia, defined as “pain or discomfort centered in the upper abdomen” is reported by one in four adults in Western societies. The most important causes are non-ulcer (functional) dyspepsia, peptic ulcer, gastroesophageal reflux, and, rarely, gastric cancer. Persons with heartburn alone are not considered to have dyspepsia. The division of dyspepsia into symptom-based subgroups (ulcer-like, dysmotility-like, reflux-like, and unnspecified dyspepsia) has proven to be of doubtful value for the clinician, as it has a low predictive value for identifying the causes of dyspepsia. Upper endoscopy remains the “gold standard” test; ultrasound and blood tests have a low yield. The role of Helicobacter pylori in peptic ulcer disease is well known, but the clinical role of the infection in non-ulcer dyspepsia remains very controversial. In uninvestigated dyspeptic patients who are H. pylori infected based on a non-invasive test, empiric anti–H. pylori therapy is a reasonable and probably cost-effective option. In documented non-ulcer dyspepsia, prokinetics are superior to placebo while antisecretory therapy is of less certain efficacy.
Mixed Chimerism and Transplantation Tolerance
Authors: Wekerle Thomas , Sykes Megan
Published: July 2002

▪ Abstract  Achieving transplanatation tolerance is an important goal in the effort to reduce long-term morbidity and mortality in organ transplant recipients. Robust, lifelong, donor-specific tolerance can be reliably achieved by induction of mixed chimerism in various animal models. To date, the clinical application of these proto-cols has been impeded partly by the potential toxicity of the required host conditioning regimens and the lack of successful studies in large animals. This article reviews the progress achieved in recent years in developing considerably milder conditioning protocols in rodents, and in extending some of these models to achieve permanent mixed chimerism and tolerance in large animals. Advances in the induction of xenogeneic tolerance through mixed chimerism are also discussed.
SURFACE RECEPTORS AND TRANSPORTERS OF TRYPANOSOMA BRUCEI
Authors: Borst P. , Fairlamb A. H.
Published: July 2002

▪ Abstract  African trypanosomes combine antigenic variation of their surface coat with the ability to take up nutrients from their mammalian hosts. Uptake of small molecules such as glucose or nucleosides is mediated by translocators hidden from host antibodies by the surface coat. The multiple glucose transporters and transporters for nucleobases and nucleosides have been characterized. Receptors for host macromolecules such as transferrin and lipoproteins are visible to antibodies but hidden from the cellular arm of the host immune system in an invagination of the trypanosome surface, the flagellar pocket. The trypanosomal transferrin receptor is a heterodimer that resembles the major component of the surface coat of Trypanosoma brucei. The ability to make several versions of this receptor allows T. brucei to bind transferrins from a range of mammals with high affinity. The proteins required for uptake of nutrients by trypanosomes provide a target for chemotherapy that remains to be fully exploited.
RESULTS FROM SHELL-MODEL MONTE CARLO STUDIES
Authors: Koonin S. E. , Dean D. J. , Langanke K.
Published: July 2002

▪ Abstract  We review results obtained using Shell-Model Monte Carlo (SMMC) techniques. These methods reduce the imaginary-time many-body evolution operator to a coherent superposition of one-body evolutions in fluctuating one-body fields; the resultant path integral is evaluated stochastically. After a brief review of the methods, we discuss a variety of nuclear-physics applications. These include studies of the ground-state properties of pf-shell nuclei, Gamow-Teller strength distributions, thermal and rotational pairing properties of nuclei near N = Z, γ-soft nuclei, and ββ-decay in76Ge. Several other illustrative calculations are also reviewed. Finally, we discuss prospects for further progress in SMMC and related calculations.
NEWLY DISCOVERED REDOX COFACTORS: Possible Nutritional, Medical, and Pharmacological Relevance to Higher Animals
Authors: McIntire William S.
Published: July 2002

▪ Abstract  Research spurred by the discovery of pyrroloquinoline quinone (PPQ) in 1979 led to the discovery of four additional oxidation-reduction (redox) cofactors, all of which result from transmogrification of amino acyl side chains in respective enzymes. These cofactors are (a) topa quinone in copper-containing amine oxidases, enzymes found in nearly all forms of life, including human; (b) lysyl topa quinone of the copper protein lysyl oxidase, an enzyme required for proper cross-linking of collagen and elastin; (c) tryptophan tryptophylquinone of alkylamine dehydrogenases from gram-negative soil bacteria; and (d) the copper-complexed cysteinyl-tyrosyl radical of fungal galactose oxidase. Originally, PQQ was thought to be a covalently bound cofactor in numerous enzymes from eukaryotes and prokaryotes. Today, PQQ is only found as a noncovalent cofactor in bacterial enzymes. The ubiquity of PQQ in the environment and its ready accessibility in the human diet has raised questions concerning its role as a vitamin, or an essential or helpful nutrient. The relevance to nutrition, medicine, and pharmacology of PQQ, topa quinone, lysyl topa quinone, tryptophan trytophylquinone, the galactose oxidase cofactor, and the enzymes harboring these cofactors are discussed in this review.
REGULATION OF FATTY ACID OXIDATION IN SKELETAL MUSCLE
Authors: Rasmussen Blake B. , Wolfe Robert R.
Published: July 2002

▪ Abstract  Researchers using animals are beginning to elucidate the control of fatty acid metabolism in muscle at the molecular and enzymatic level. This review examines the physiological data that has been collected from human subjects in the context of the proposed control mechanisms. A number of factors, including the availability of free fatty acids and the abundance of fatty acid transporters, may influence the rate of muscle fatty acid oxidation. However, the predominant point of control appears to be the rate at which fatty acyl–coenzyme A is transported into the mitochondria by the carnitine palmitoyl transferase system. In turn, evidence suggests that the intracellular concentration of malonyl–coenzyme A in muscle is an important regulator of carnitine palmitoyl transferase–I activity. Malonyl–coenzyme A is increased by glucose, which is likely the mechanism whereby glucose intake suppresses the transfer of fatty acids into the mitochondria for subsequent oxidation. In contrast, malonyl–coenzyme A levels decrease during exercise, which enables increased fatty acid oxidation. However, for any given carnitine palmitoyl transferase–I activity, there may be an effect of free fatty acid availability on fatty acid oxidation, particularly at low levels of free fatty acids. Nonetheless, the rate of glucose or glycogen metabolism is probably the primary regulator of the balance between glucose and fatty acid oxidation in muscle.
Intestinal Transport During Fasting and Malnutrition
Authors: Ferraris Ronaldo P. , Carey Hannah V.
Published: July 2002

Fasting or malnutrition (FM) has dramatic effects on small intestinal mucosal structure and transport function. Intestinal secretion of ions and fluid is increased by FM both under basal conditions and in response to secretory agonists. Intestinal permeability to ions and macromolecules may also be elevated by FM, which increases the potential for fluid and electrolyte losses and for anaphylactic responses to luminal antigens. Mucosal atrophy induced by FM reduces total intestinal absorption of nutrients, but nutrient absorption normalized to mucosal mass may actually be enhanced by a variety of mechanisms, including increased transporter gene expression, electrochemical gradients, and ratio of mature to immature cells. These observations underscore the value of enteral feeding during health and disease.
NUTRITIONALIMPACT OFPRE- ANDPROBIOTICS ASPROTECTIVEGASTROINTESTINALORGANISMS
Authors: Teitelbaum Jonathan E. , Walker W. Allan
Published: July 2002

▪ Abstract  The health benefits of pre- and probiotics have been the subject of increased research interests. These food supplements have been demonstrated to alter the pre-existing intestinal flora so as to provide an advantage to the host. This review focuses on the scientific evidence both for and against their role in promoting health and treating disease. Specific attention is turned to their effects on immunomodulation, lipid metabolism, cancer prevention, diarrhea, Helicobacter pylori, necrotizing enterocolitis, allergy, and inflammatory bowel disease.
G PROTEIN βγ SUBUNITS
Authors: Clapham David E. , Neer Eva J.
Published: July 2002

▪ Abstract  Guanine nucleotide binding (G) proteins relay extracellular signals encoded in light, small molecules, peptides, and proteins to activate or inhibit intracellular enzymes and ion channels. The larger G proteins, made up of Gαβγ heterotrimers, dissociate into Gα and Gβγ subunits that separately activate intracellular effector molecules. Only recently has the Gβγ subunit been recognized as a signal transduction molecule in its own right; Gβγ is now known to directly regulate as many different protein targets as the Gα subunit. Recent X-ray crystallography of Gα, Gβγ, and Gαβγ subunits will guide the investigation of structure-function relationships.
Lysophospholipid Receptors
Authors: Fukushima Nobuyuki , Ishii Isao , Contos James JA , Weiner Joshua A , Chun Jerold
Published: July 2002

Lysophospholipids (LPs), including lysophosphatidic acid and sphingosine 1-phosphate, produce many cellular effects. However, the prolonged absence of any cloned and identified LP receptor has left open the question of how these lipids actually bring about these effects. The cloning and functional identification of the first LP receptor, lpA1/vzg-1, has led rapidly to the identification and classification of multiple orphan receptors/expression sequence tags known by many names (e.g. edg, mrec1.3, gpcr26, H218, AGR16, nrg-1) as members of a common cognate G protein-coupled receptor family. We review features of the LP receptor family, including molecular characteristics, genomics, signaling properties, and gene expression. A major question for which only partial answers are available concerns the biological significance of receptor-mediated LP signaling. Recent studies that demonstrate the role of receptor-mediated LP signaling in the nervous system, cardiovascular system, and other organ systems indicate the importance of this signaling in development, function, and pathophysiology and portend an exciting time ahead for this growing field.
Nonlinear Kinetics and New Approaches to Complex Reaction Mechanisms
Authors: Ross John , Vlad Marcel O.
Published: July 2002

▪ Abstract  This paper reviews recent developments in the field of nonlinear chemical kinetics. Five topics are dealt with: (a) new approaches to complex reaction mechanisms, stoichiometric network analysis, classification of chemical oscillators and formulation of their mechanisms by deduction from experiments, and correlation metric construction of reaction pathways from measurements; (b) thermodynamic and stochastic theory of nonequilibrium processes, the eikonal approximation, the evaluation of stochastic potentials, experimental tests of the thermodynamic and stochastic theory of relative stability, and fluctuation-dissipation relations in nonequilibrium chemical systems; (c) chemical kinetics and cellular automata and lattice gas automata; (d) theoretical approaches and experimental studies of stochastic resonance in chemical kinetics; and (e) rate processes in disordered systems, stochastic Liouville equations, stretched exponential relaxation in disordered systems, and universality classes for rate processes in systems with static or dynamic disorder.
FUNCTION OF ROOT BORDER CELLS IN PLANT HEALTH: Pioneersin the Rhizosphere
Authors: Hawes M. C. , Brigham L. A. , Wen F. , Woo H. H. , Zhu Y.
Published: July 2002

▪ Abstract  Plants dedicate a large amount of energy to the regulated production of living cells programmed to separate from roots into the external environment. This unusual process may be worth the cost because it enables the plant to dictate which species will share its ecological niche. For example, border cells can rapidly attract and stimulate growth in some microorganisms and repel and inhibit the growth of others. Such specificity may provide a way to control the dynamics of adjacent microbial populations in the soil to foster beneficial associations and inhibit pathogenic invasion. Plant genes controlling the delivery of border cells and the expression of their unique properties provide tools to genetically engineer plants with altered border cell quality and quantity. Such variants are being used to test the hypothesis that the function of border cells is to protect plant health by controlling the ecology of the root system.
ISAIAH BERLIN: Political Theory and Liberal Culture
Authors: Ryan Alan
Published: July 2002

▪ Abstract  The essay provides a short outline of Berlin's career and an assessment of his contribution to pluralist and liberal thought. He was a British academic with a Russian cast of mind, and an inhabitant of the ivory tower who was very much at home in the diplomatic and political world. Similarly, he was neither a historian of ideas nor a political philosopher in the narrow sense usually understood in the modern academy. Rather, he engaged in a trans-historical conversation about the human condition with such figures as Machiavelli, Herzen, Vico, and Herder. The Russian liberal understanding of the historical and cultural setting was, in his view, much superior to that of familiar figures such as John Stuart Mill, just as the nonliberal Machiavelli cast a particularly vivid light on the problems of a pluralist world view.
Electoral Realignments
Authors: Mayhew David R.
Published: July 2002

American electoral realignment theory, as constructed in its classic form chiefly by Key, Schattschneider, Sundquist, and Burnham, can be sorted into 11 distinct empirical claims. These pertain to dichotomization of election types, periodicity, a cyclical dynamic, high voter turnout, durable new issue cleavages, ideologized elections, nationalization of issues, major changes in government policy, redistributive policy, effective and consequential voter voice, and the “system of 1896.” These claims are assessed for their empirical validity and illuminative power.
Evaluating the State Children's Health Insurance Program: Critical Considerations
Authors: Starfield Barbara
Published: July 2002

▪ Abstract  The Balanced Budget Act of August 1997 was intended to improve the insurance coverage of low-income children. Although no specific mandates for evaluation accompanied the legislation, states are expected to assess its impact. Insurance improves access to and use of health services. The extent to which this is associated with better health depends on the kinds of services received. Access to a regular source of care is a critical characteristic. If this source of care provides good primary care, a variety of benefits would be expected to accrue. Thus, evaluation of the benefits of the State Children's Health Insurance Program should address not only improved coverage by health insurance for eligible children, but also the extent to which children receive high-quality primary care, including appropriate referrals when needed. Maternal access to and use of services is also a critical factor. Targets for evaluation include state activities to (a) enroll through outreach, inform through education, and develop information systems for tracking; (b) assess the degree of penetration of insurance among low-income children and their mothers, the availability of health care personnel, and the adequacy of benefits conferred by the insurance, primary-care services, and back-up specialty services; and (c) obtain evidence of improved health status. This article details approaches that can appropriately be used to address each of these aspects of concern.