bluuebunny/crossref_metadata_2025 huggingface dataset:
Reasoning with higher-order abstract syntax in a logical framework
Authors: McDowell Raymond C. , Miller Dale A.
Published: July 2002

Logical frameworks based on intuitionistic or linear logics with higher-type quantification have been successfully used to give high-level, modular, and formal specifications of many important judgments in the area of programming languages and inference systems. Given such specifications, it is natural to consider proving properties about the specified systems in the framework: for example, given the specification of evaluation for a functional programming language, prove that the language is deterministic or that evaluation preserves types. One challenge in developing a framework for such reasoning is that
higher-order abstract syntax
(HOAS), an elegant and declarative treatment of object-level abstraction and substitution, is difficult to treat in proofs involving induction. In this article, we present a meta-logic that can be used to reason about judgments coded using HOAS; this meta-logic is an extension of a simple intuitionistic logic that admits higher-order quantification over simply typed λ-terms (key ingredients for HOAS) as well as induction and a notion of
definition
. The latter concept of definition is a proof-theoretic device that allows certain theories to be treated as "closed" or as defining fixed points. We explore the difficulties of formal meta-theoretic analysis of HOAS encodings by considering encodings of intuitionistic and linear logics, and formally derive the admissibility of cut for important subsets of these logics. We then propose an approach to avoid the apparent trade-off between the benefits of higher-order abstract syntax and the ability to analyze the resulting encodings. We illustrate this approach through examples involving the simple functional and imperative programming languages PCF and PCF
:=
. We formally derive such properties as unicity of typing, subject reduction, determinacy of evaluation, and the equivalence of transition semantics and natural semantics presentations of evaluation.
Machine learning in automated text categorization
Authors: Sebastiani Fabrizio
Published: July 2002

The automated categorization (or classification) of texts into predefined categories has witnessed a booming interest in the last 10 years, due to the increased availability of documents in digital form and the ensuing need to organize them. In the research community the dominant approach to this problem is based on machine learning techniques: a general inductive process automatically builds a classifier by learning, from a set of preclassified documents, the characteristics of the categories. The advantages of this approach over the knowledge engineering approach (consisting in the manual definition of a classifier by domain experts) are a very good effectiveness, considerable savings in terms of expert labor power, and straightforward portability to different domains. This survey discusses the main approaches to text categorization that fall within the machine learning paradigm. We will discuss in detail issues pertaining to three different problems, namely, document representation, classifier construction, and classifier evaluation.
Expert systems for configuration at Digital: XCON and beyond
Authors: Barker Virginia E. , O'Connor Dennis E. , Bachant Judith , Soloway Elliot
Published: July 2002

Members of Digital Equipment Corporation's team of expert system experts reflect and recount a decade's worth of lessons learned in designing, and building a core of configuration systems
Efficient algorithms for finding maximum matching in graphs
Authors: Galil Zvi
Published: July 2002

This paper surveys the techniques used for designing the most efficient algorithms for finding a maximum cardinality or weighted matching in (general or bipartite) graphs. It also lists some open problems concerning possible improvements in existing algorithms and the existence of fast parallel algorithms for these problems.
Learning to program = learning to construct mechanisms and explanations
Authors: Soloway E.
Published: July 2002

Teaching effective problem-solving skills in the context of teaching programming necessitates a revised curriculum for introductory computer programming courses.
Transaction management in the R* distributed database management system
Authors: Mohan C. , Lindsay B. , Obermarck R.
Published: July 2002

This paper deals with the transaction management aspects of the R* distributed database system. It concentrates primarily on the description of the R
*
commit protocols, Presumed Abort (PA) and Presumed Commit (PC). PA and PC are extensions of the well-known, two-phase (2P) commit protocol. PA is optimized for read-only transactions and a class of multisite update transactions, and PC is optimized for other classes of multisite update transactions. The optimizations result in reduced intersite message traffic and log writes, and, consequently, a better response time. The paper also discusses R
*
's approach toward distributed deadlock detection and resolution.
A compression technique to materialize transitive closure
Authors: Jagadish H. V.
Published: July 2002

An important feature of database support for expert systems is the ability of the database to answer queries regarding the existence of a path from one node to another in the directed graph underlying some database relation. Given just the database relation, answering such a query is time-consuming, but given the transitive closure of the database relation a table look-up suffices. We present an indexing scheme that permits the storage of the pre-computed transitive closure of a database relation in a compressed form. The existence of a specified tuple in the closure can be determined from this compressed store by a single look-up followed by an index comparision. We show how to add nodes and arcs to the compressed closure incrementally. We also suggest how this compression technique can be used to reduce the effort required to compute the transitive closure.
The Archaeology of Ancient Religion in the Eastern Woodlands
Authors: Brown James A.
Published: July 2002

Archaeology has begun to contribute to the history of spirituality in the Eastern Woodlands of North America to complement the perspectives offered by the comparative study of religions and by ethnological, folkloric, art historical, and astronomical research. Support can be found in the forms and types of ritual paraphernalia and in the associated iconography for the thesis that shamanism was a basic form of religious experience that extended back to the earliest material traces. Elaborations upon this foundation became most conspicuous during the Mississippian Period when social hierarchies developed upon an expanded, agriculturally supported population. Animal imagery changed, ancestor cults became elaborated, and cosmography took on increased importance in architecture, site layout, and mortuary rites. The canonical forms of the iconography of this period have become known as the Southeastern Ceremonial Complex. Since European contact, practices and beliefs associated with social hierarchies have disappeared or transformed.
Whither Primatology? The Place of Primates in Contemporary Anthropology
Authors: Rodman P. S.
Published: July 2002

▪ Abstract  Primatology in anthropology began with morphological comparisons of primates to reconstruct the evolution of humans. Naturalistic studies started in the mid-twentieth century and contributed to understanding the functions of morphological variations. Today, research in primatology employs the new paradigm of behavioral ecology and sociobiology for analysis and interpretation of variation in behavior and ecology. Grouping and group sizes of primates are explained with reference to effects of predation, defense of resources, and female defense against male infanticide. Primates avoid close consanguineous mating, usually by dispersal of males from the birthplace, though in bonobos and chimpanzees males are philopatric. In many primates, nepotistic relations among females are explained by kin selection operating on the philopatric sex. In chimpanzees, nepotism is clearest among the philopatric males. Sexual dimorphism, dominance hierarchies, intrasexual competition, and particularly infanticide by males are best explained by the action of sexual selection. Comparative studies of primates indicate that the large brains of the genus Homo (enlarged cerebral cortex) evolved after bipedalism and human dental characters and probably depended on high-quality diets. Broad comparative studies have supported the hypothesis that large brains may have evolved in response to complex social environments, but comparisons within the apes only may not support the hypothesis. Although dominant themes of current anthropology are not compatible with the epistemology, theory, or methodology of primate research and interpretation, primate studies fit easily within the future of anthropology as a four-field evolutionary study of the origins of humans and human nature.
The Commodification of the Body and its Parts
Authors: Sharp Lesley A.
Published: July 2002

▪ Abstract  The human body—and its parts—has long been a target for commodification within myriad cultural settings. A discussion of commodification requires that one consider, first, the significance of the body within anthropology and, second, what defines a body “part.” After exploring these initial questions, this article outlines dominant theoretical approaches to commodification within anthropology, with Mauss and Marx figuring prominently. The discussion then turns to historically well-documented forms of body commodification: These include slavery and other oppressive labor practices; female reproduction; and the realms of sorcery and endocannibalism. An analysis here uncovers dominant established approaches that continue to drive current studies. The remainder of this article concerns emergent biotechnologies, whose application in clinical and other related scientific arenas marks a paradigmatic shift in anthropological understandings of the commodified, fragmented body. The following contexts are explored with care: reproductive technologies; organ transplantation; cosmetic and transsexual surgeries; genetics and immunology; and, finally, the category of the cyborg. The article concludes with suggestions for an integrated theoretical vision, advocating greater cross-fertilization of analytical approaches and the inclusion of an ethics of body commodification within anthropology.
PHYSIOLOGY OF ION TRANSPORT ACROSS THE TONOPLAST OF HIGHER PLANTS
Authors: Barkla Bronwyn J. , Pantoja Omar
Published: July 2002

▪ Abstract  The vacuole of plant cells plays an important role in the homeostasis of the cell. It is involved in the regulation of cytoplasmic pH, sequestration of toxic ions and xenobiotics, regulation of cell turgor, storage of amino acids, sugars and CO2 in the form of malate, and possibly as a source for elevating cytoplasmic calcium. All these activities are driven by two primary active transport mechanisms present in the vacuolar membrane (tonoplast). These two mechanisms employ high-energy metabolites to pump protons into the vacuole, establishing a proton electrochemical potential that mediates the transport of a diverse range of solutes. Within the past few years, great advances at the molecular and functional levels have been made on the characterization and identification of these mechanisms. The aim of this review is to summarize these studies in the context of the physiology of the plant cell.
THE MOLECULAR BASIS OF DEHYDRATION TOLERANCE IN PLANTS
Authors: Ingram J. , Bartels D.
Published: July 2002

▪ Abstract  Molecular studies of drought stress in plants use a variety of strategies and include different species subjected to a wide range of water deficits. Initial research has by necessity been largely descriptive, and relevant genes have been identified either by reference to physiological evidence or by differential screening. A large number of genes with a potential role in drought tolerance have been described, and major themes in the molecular response have been established. Particular areas of importance are sugar metabolism and late-embryogenesis-abundant (LEA) proteins. Studies have begun to examine mechanisms that control the gene expression, and putative regulatory pathways have been established. Recent attempts to understand gene function have utilized transgenic plants. These efforts are of clear agronomic importance.
CARBOHYDRATE-MODULATED GENE EXPRESSION IN PLANTS
Authors: Koch K. E.
Published: July 2002

▪ Abstract  Plant gene responses to changing carbohydrate status can vary markedly. Some genes are induced, some are repressed, and others are minimally affected. As in microorganisms, sugar-sensitive plant genes are part of an ancient system of cellular adjustment to critical nutrient availability. However, in multicellular plants, sugar-regulated expression also provides a mechanism for control of resource distribution among tissues and organs. Carbohydrate depletion upregulates genes for photosynthesis, remobilization, and export, while decreasing mRNAs for storage and utilization. Abundant sugar levels exert opposite effects through a combination of gene repression and induction. Long-term changes in metabolic activity, resource partitioning, and plant form result. Sensitivity of carbohydrate-responsive gene expression to environmental and developmental signals further enhances its potential to aid acclimation. The review addresses the above from molecular to whole-plant levels and considers emerging models for sensing and transducing carbohydrate signals to responsive genes.
REGULATION OF FATTY ACID SYNTHESIS
Authors: Ohlrogge John B. , Jaworski Jan G.
Published: July 2002

▪ Abstract  All plant cells produce fatty acids from acetyl-CoA by a common pathway localized in plastids. Although the biochemistry of this pathway is now well understood, much less is known about how plants control the very different amounts and types of lipids produced in different tissues. Thus, a central challenge for plant lipid research is to provide a molecular understanding of how plants regulate the major differences in lipid metabolism found, for example, in mesophyll, epidermal, or developing seed cells. Acetyl-CoA carboxylase (ACCase) is one control point that regulates rates of fatty acid synthesis. However, the biochemical modulators that act on ACCase and the factors that in turn control these modulators are poorly understood. In addition, little is known about how the expression of genes involved in fatty acid synthesis is controlled. This review evaluates current knowledge of regulation of plant fatty metabolism and attempts to identify the major unanswered questions.
AQUAPORINS AND WATER PERMEABILITY OF PLANT MEMBRANES
Authors: Maurel Christophe
Published: July 2002

▪ Abstract  The mechanisms of plant membrane water permeability have remained elusive until the recent discovery in both vacuolar and plasma membranes of a class of water channel proteins named aquaporins. Similar to their animal counterparts, plant aquaporins have six membrane-spanning domains and belong to the MIP superfamily of transmembrane channel proteins. Their very high efficiency and selectivity in transporting water molecules have been mostly characterized using heterologous expression in Xenopus oocytes. However, techniques set up to measure the osmotic water permeability of plant membranes such as transcellular osmosis, pressure probe measurements, or stopped-flow spectrophotometry are now being used to analyze the function of plant aquaporins in their native membranes. Multiple mechanisms, at the transcriptional and posttranslational levels, control the expression and activity of the numerous aquaporin isoforms found in plants. These studies suggest a general role for aquaporins in regulating transmembrane water transport during the growth, development, and stress responses of plants. Future research will investigate the integrated function of aquaporins in long-distance water transport and cellular osmoregulation.
STRUCTURE AND MEMBRANE ORGANIZATION OF PHOTOSYSTEM II IN GREEN PLANTS
Authors: Hankamer Ben , Barber James , Boekema Egbert J.
Published: July 2002

▪ Abstract  Photosystem II (PSII) is the pigment protein complex embedded in the thylakoid membrane of higher plants, algae, and cyanobacteria that uses solar energy to drive the photosynthetic water-splitting reaction. This chapter reviews the primary, secondary, tertiary, and quaternary structures of PSII as well as the function of its constituent subunits. The understanding of in vivo organization of PSII is based in part on freeze-etched and freeze-fracture images of thylakoid membranes. These images show a resolution of about 40–50 Å and so provide information mainly on the localization, heterogeneity, dimensions, and shapes of membrane-embedded PSII complexes. Higher resolution of about 15–40 Å has been obtained from single particle images of isolated PSII complexes of defined and differing subunit composition and from electron crystallography of 2-D crystals. Observations are discussed in terms of the oligomeric state and subunit organization of PSII and its antenna components.
BRASSINOSTEROIDS: Essential Regulators of Plant Growth and Development
Authors: Clouse Steven D. , Sasse Jenneth M.
Published: July 2002

▪ Abstract  Brassinosteroids (BRs) are growth-promoting natural products found at low levels in pollen, seeds, and young vegetative tissues throughout the plant kingdom. Detailed studies of BR biosynthesis and metabolism, coupled with the recent identification of BR-insensitive and BR-deficient mutants, has greatly expanded our view of steroids as signals controlling plant growth and development. This review examines the microchemical and molecular genetic analyses that have provided convincing evidence for an essential role of BRs in diverse developmental programs, including cell expansion, vascular differentiation, etiolation, and reproductive development. Recent advances relevant to the molecular mechanisms of BR-regulated gene expression and BR signal transduction are also discussed.
NITRATE REDUCTASE STRUCTURE, FUNCTION AND REGULATION: Bridging the Gap between Biochemistry and Physiology
Authors: Campbell Wilbur H.
Published: July 2002

▪ Abstract  Nitrate reductase (NR; EC 1.6.6.1-3) catalyzes NAD(P)H reduction of nitrate to nitrite. NR serves plants, algae, and fungi as a central point for integration of metabolism by governing flux of reduced nitrogen by several regulatory mechanisms. The NR monomer is composed of a ∼100-kD polypeptide and one each of FAD, heme-iron, and molybdenum-molybdopterin (Mo-MPT). NR has eight sequence segments: (a) N-terminal “acidic” region; (b) Mo-MPT domain with nitrate-reducing active site; (c) interface domain; (d) Hinge 1 containing serine phosphorylated in reversible activity regulation with inhibition by 14-3-3 binding protein; (e) cytochrome b domain; (f) Hinge 2; (g) FAD domain; and (h) NAD(P)H domain. The cytochrome b reductase fragment contains the active site where NAD(P)H transfers electrons to FAD. A complete three-dimensional dimeric NR structure model was built from structures of sulfite oxidase and cytochrome b reductase. Key active site residues have been investigated. NR structure, function, and regulation are now becoming understood.
THE GREAT ESCAPE: Phloem Transport and Unloading of Macromolecules
Authors: Oparka Karl J. , Cruz Simon Santa
Published: July 2002

▪ Abstract  The phloem of higher plants translocates a diverse range of macromolecules including proteins, RNAs, and pathogens. This review considers the origin and destination of such macromolecules. A survey of the literature reveals that the majority of phloem-mobile macromolecules are synthesized within companion cells and enter the sieve elements through the branched plasmodesmata that connect these cells. Examples of systemic macromolecules that originate outside the companion cell are rare and are restricted to viral and subviral pathogens and putative RNA gene-silencing signals, all of which involve a relay system in which the macromolecule is amplified in each successive cell along the pathway to companion cells. Evidence is presented that xenobiotic macromolecules may enter the sieve element by a default pathway as they do not possess the necessary signals for retention in the sieve element–companion cell complex. Several sink tissues possess plasmodesmata with a high-molecular-size exclusion limit, potentially allowing the nonspecific escape of a wide range of small (<50-kDa) macromolecules from the phloem. Larger macromolecules and systemic mRNAs appear to require facilitated transport through sink plasmodesmata. The fate of phloem-mobile macromolecules is considered in relation to current models of long-distance signaling in plants.
MACRONUTRIENT UTILIZATION BY PHOTOSYNTHETIC EUKARYOTES AND THE FABRIC OF INTERACTIONS
Authors: Grossman Arthur , Takahashi Hideki
Published: July 2002

▪ Abstract  Organisms acclimate to a continually fluctuating nutrient environment. Acclimation involves responses specific for the limiting nutrient as well as responses that are more general and occur when an organism experiences different stress conditions. Specific responses enable organisms to efficiently scavenge the limiting nutrient and may involve the induction of high-affinity transport systems and the synthesis of hydrolytic enzymes that facilitate the release of the nutrient from extracellular organic molecules or from internal reserves. General responses include changes in cell division rates and global alterations in metabolic activities. In photosynthetic organisms there must be precise regulation of photosynthetic activity since when severe nutrient limitation prevents continued cell growth, excitation of photosynthetic pigments could result in the formation of reactive oxygen species, which can severely damage structural and functional features of the cell. This review focuses on ways that photosynthetic eukaryotes assimilate the macronutrients nitrogen, sulfur, and phosphorus, and the mechanisms that govern assimilatory activities. Also discussed are molecular responses to macronutrient limitation and the elicitation of those responses through integration of environmental and cellular cues.
FUNCTION AND MECHANISM OF ORGANIC ANION EXUDATION FROM PLANT ROOTS
Authors: Ryan PR , Delhaize E , Jones DL
Published: July 2002

▪ Abstract  The rhizosphere is the zone of soil immediately surrounding plant roots that is modified by root activity. In this critical zone, plants perceive and respond to their environment. As a consequence of normal growth and development, a large range of organic and inorganic substances are exchanged between the root and soil, which inevitably leads to changes in the biochemical and physical properties of the rhizosphere. Plants also modify their rhizosphere in response to certain environmental signals and stresses. Organic anions are commonly detected in this region, and their exudation from plant roots has now been associated with nutrient deficiencies and inorganic ion stresses. This review summarizes recent developments in the understanding of the function, mechanism, and regulation of organic anion exudation from roots. The benefits that plants derive from the presence of organic anions in the rhizosphere are described and the potential for biotechnology to increase organic anion exudation is highlighted.
Theory of Low-Mass Stars and Substellar Objects
Authors: Chabrier Gilles , Baraffe Isabelle
Published: July 2002

▪ Abstract  Since the discovery of the first bona-fide brown dwarfs and extra-solar planets in 1995, the field of low-mass stars and substellar objects has progressed considerably, both from theoretical and observational viewpoints. Recent developments in the physics entering the modeling of these objects have led to significant improvements in the theory and to a better understanding of these objects' mechanical and thermal properties. This theory can now be confronted with observations directly in various observational diagrams (color-color, color-magnitude, mass-magnitude, mass-spectral type), a stringent and unavoidable constraint that became possible only recently with the generation of synthetic spectra. In this paper we present the current state-of-the-art general theory of low-mass stars and sub stellar objects, from one solar mass to one Jupiter mass, regarding primarily their interior structure and evolution. This review is a natural complement to the previous review by Allard et al (1997) on the atmosphere of low-mass stars and brown dwarfs. Special attention is devoted to the comparison of the theory with various available observations. The contribution of low-mass stellar and sub stellar objects to the Galactic mass budget is also analyzed.
Winds from Hot Stars
Authors: Kudritzki Rolf-Peter , Puls Joachim
Published: July 2002

▪ Abstract  This review deals with the winds from “normal” hot stars such as O-stars, B- and A-supergiants, and Central Stars of Planetary Nebulae with O-type spectra. The advanced diagnostic methods of stellar winds, including an assessment of the accuracy of the determinations of global stellar wind parameters (terminal velocities, mass-loss rates, wind momenta, and energies), are introduced and scaling relations as a function of stellar parameters are provided. Observational results are interpreted in the framework of the stationary, one-dimensional (1-D) theory of line-driven winds. Systematic effects caused by nonhomogeneous structures, time dependence, and deviations from spherical symmetry are discussed. The review finishes with a brief description of the role of stellar winds as extragalactic distance indicators and as tracers of the chemical composition of galaxies at high redshift.
Cellular and Molecular Biology of the Aquaporin Water Channels
Authors: Borgnia Mario , Nielsen Søren , Engel Andreas , Agre Peter
Published: July 2002

▪ Abstract  The high water permeability characteristic of mammalian red cell membranes is now known to be caused by the protein AQP1. This channel freely permits movement of water across the cell membrane, but it is not permeated by other small, uncharged molecules or charged solutes. AQP1 is a tetramer with each subunit containing an aqueous pore likened to an hourglass formed by obversely arranged tandem repeats. Cryoelectron microscopy of reconstituted AQP1 membrane crystals has revealed the three-dimensional structure at 3–6 Å. AQP1 is distributed in apical and basolateral membranes of renal proximal tubules and descending thin limbs as well as capillary endothelia. Ten mammalian aquaporins have been identified in water-permeable tissues and fall into two groupings. Orthodox aquaporins are water-selective and include AQP2, a vasopressin-regulated water channel in renal collecting duct, in addition to AQP0, AQP4, and AQP5. Multifunctional aquaglyceroporins AQP3, AQP7, and AQP9 are permeated by water, glycerol, and some other solutes. Aquaporins are being defined in numerous other species including amphibia, insects, plants, and microbials. Members of the aquaporin family are implicated in numerous physiological processes as well as the pathophysiology of a wide range of clinical disorders.
CREB: A Stimulus-Induced Transcription Factor Activated by A Diverse Array of Extracellular Signals
Authors: Shaywitz Adam J. , Greenberg Michael E.
Published: July 2002

▪ Abstract  Extracellular stimuli elicit changes in gene expression in target cells by activating intracellular protein kinase cascades that phosphorylate transcription factors within the nucleus. One of the best characterized stimulus-induced transcription factors, cyclic AMP response element (CRE) -binding protein (CREB), activates transcription of target genes in response to a diverse array of stimuli, including peptide hormones, growth factors, and neuronal activity, that activate a variety of protein kinases including protein kinase A (PKA), pp90 ribosomal S6 kinase (pp90RSK), and Ca2+/calmodulin-dependent protein kinases (CaMKs). These kinases all phosphorylate CREB at a particular residue, serine 133 (Ser133), and phosphorylation of Ser133 is required for CREB-mediated transcription. Despite this common feature, the mechanism by which CREB activates transcription varies depending on the stimulus. In some cases, signaling pathways target additional sites on CREB or proteins associated with CREB, permitting CREB to regulate distinct programs of gene expression under different conditions of stimulation. This review will discuss the molecular mechanisms by which Ser133--phosphorylated CREB activates transcription, intracellular signaling pathways that lead to phosphorylation of CREB at Ser133, and features of each signaling pathway that impart specificity at the level of CREB activation.
Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin
Authors: Skehel John J. , Wiley Don C.
Published: July 2002

▪ Abstract  Hemagglutinin (HA) is the receptor-binding and membrane fusion glycoprotein of influenza virus and the target for infectivity-neutralizing antibodies. The structures of three conformations of the ectodomain of the 1968 Hong Kong influenza virus HA have been determined by X-ray crystallography: the single-chain precursor, HA0; the metastable neutral-pH conformation found on virus, and the fusion pH-induced conformation. These structures provide a framework for designing and interpreting the results of experiments on the activity of HA in receptor binding, the generation of emerging and reemerging epidemics, and membrane fusion during viral entry. Structures of HA in complex with sialic acid receptor analogs, together with binding experiments, provide details of these low-affinity interactions in terms of the sialic acid substituents recognized and the HA residues involved in recognition. Neutralizing antibody-binding sites surround the receptor-binding pocket on the membrane-distal surface of HA, and the structures of the complexes between neutralizing monoclonal Fabs and HA indicate possible neutralization mechanisms. Cleavage of the biosynthetic precursor HA0 at a prominent loop in its structure primes HA for subsequent activation of membrane fusion at endosomal pH ( Figure 1 ). Priming involves insertion of the fusion peptide into a charged pocket in the precursor; activation requires its extrusion towards the fusion target membrane, as the N terminus of a newly formed trimeric coiled coil, and repositioning of the C-terminal membrane anchor near the fusion peptide at the same end of a rod-shaped molecule. Comparison of this new HA conformation, which has been formed for membrane fusion, with the structures determined for other virus fusion glycoproteins suggests that these molecules are all in the fusion-activated conformation and that the juxtaposition of the membrane anchor and fusion peptide, a recurring feature, is involved in the fusion mechanism. Extension of these comparisons to the soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) protein complex of vesicle fusion allows a similar conclusion.

[Figure: see text]
Replisome-Mediated DNA Replication
Authors: Benkovic Stephen J. , Valentine Ann M. , Salinas Frank
Published: July 2002

▪ Abstract  The elaborate process of genomic replication requires a large collection of proteins properly assembled at a DNA replication fork. Several decades of research on the bacterium Escherichia coli and its bacteriophages T4 and T7 have defined the roles of many proteins central to DNA replication. These three different prokaryotic replication systems use the same fundamental components for synthesis at a moving DNA replication fork even though the number and nature of some individual proteins are different and many lack extensive sequence homology. The components of the replication complex can be grouped into functional categories as follows: DNA polymerase, helix destabilizing protein, polymerase accessory factors, and primosome (DNA helicase and DNA primase activities). The replication of DNA derives from a multistep enzymatic pathway that features the assembly of accessory factors and polymerases into a functional holoenzyme; the separation of the double-stranded template DNA by helicase activity and its coupling to the primase synthesis of RNA primers to initiate Okazaki fragment synthesis; and the continuous and discontinuous synthesis of the leading and lagging daughter strands by the polymerases. This review summarizes and compares and contrasts for these three systems the types, timing, and mechanism of reactions and of protein-protein interactions required to initiate, control, and coordinate the synthesis of the leading and lagging strands at a DNA replication fork and comments on their generality.
Divergent Evolution of Enzymatic Function: Mechanistically Diverse Superfamilies and Functionally Distinct Suprafamilies
Authors: Gerlt John A. , Babbitt Patricia C.
Published: July 2002

▪ Abstract  The protein sequence and structure databases are now sufficiently representative that strategies nature uses to evolve new catalytic functions can be identified. Groups of divergently related enzymes whose members catalyze different reactions but share a common partial reaction, intermediate, or transition state (mechanistically diverse superfamilies) have been discovered, including the enolase, amidohydrolase, thiyl radical, crotonase, vicinal-oxygen-chelate, and Fe-dependent oxidase superfamilies. Other groups of divergently related enzymes whose members catalyze different overall reactions that do not share a common mechanistic strategy (functionally distinct suprafamilies) have also been identified: (a) functionally distinct suprafamilies whose members catalyze successive transformations in the tryptophan and histidine biosynthetic pathways and (b) functionally distinct suprafamilies whose members catalyze different reactions in different metabolic pathways. An understanding of the structural bases for the catalytic diversity observed in super- and suprafamilies may provide the basis for discovering the functions of proteins and enzymes in new genomes as well as provide guidance for in vitro evolution/engineering of new enzymes.
Engineering and Material Considerations in Islet Cell Transplantation
Authors: Chaikof Elliot L.
Published: July 2002

▪ Abstract  The successful application and optimization of cell transplantation will require quantitative engineering design and analysis of cells and materials in which relevant biological processes remain complex and incompletely defined. This report primarily reviews the engineering and material considerations in islet cell transplantation, including established biological constraints and biohybrid devices for cell delivery, as well as available barrier materials and the associated processing strategies directed at the control of solute transport, barrier permeability, and host responses at the biological–material interface. Also described are current areas of investigation with particular promise as enabling technologies for accelerating the clinical effectiveness of islet cell transplantation.
HIERARCHY AND DYNAMICS OF RNA FOLDING
Authors: Brion Philippe , Westhof Eric
Published: July 2002

▪ Abstract  The evidence showing that the self-assembly of complex RNAs occurs in discrete transitions, each relating to the folding of sub-systems of increasing size and complexity starting from a state with most of the secondary structure, is reviewed. The reciprocal influence of the concentration of magnesium ions and nucleotide mutations on tertiary structure is analyzed. Several observations demonstrate that detrimental mutations can be rescued by high magnesium concentrations, while stabilizing mutations lead to a lesser dependence on magnesium ion concentration. Recent data point to the central controlling and monitoring roles of RNA-binding proteins that can bind to the different folding stages, either before full establishment of the secondary structure or at the molten globule state before the cooperative transition to the final three-dimensional structure.
ORGANIZING SPATIAL PATTERN IN LIMB DEVELOPMENT
Authors: Brook William J. , Diaz-Benjumea Fernando J. , Cohen Stephen M.
Published: July 2002

▪ Abstract  Recent studies on the development of the legs and wings of Drosophila have led to the conclusion that insect limb development is controlled by localized pattern organizing centers, analogous to those identified in vertebrate embryos. Genetic analysis has defined the events that lead to the formation of these organizing centers and has led to the identification of gene products that mediate organizer function. The possibility of homology between vertebrate and insect limbs is considered in light of recently reported similarities in patterns of gene expression and function.
THE DESIGN PLAN OF KINESIN MOTORS
Authors: Vale Ronald D. , Fletterick Robert J.
Published: July 2002

▪ Abstract  The kinesin superfamily comprises a large and structurally diverse group of microtubule-based motor proteins that produce a variety of force-generating activities within cells. This review addresses how the structures of kinesin proteins provide clues as to their biological functions and motile properties. We discuss structural features common to all kinesin motors, as well as specialized features that enable subfamilies of related motors to carry out specialized activities. We also discuss how the kinesin motor domain uses chemical energy from ATP hydrolysis to move along microtubules.
FUNCTIONS OF LIPID RAFTS IN BIOLOGICAL MEMBRANES
Authors: Brown D. A. , London E.
Published: July 2002

▪ Abstract  Recent studies showing that detergent-resistant membrane fragments can be isolated from cells suggest that biological membranes are not always in a liquid-crystalline phase. Instead, sphingolipid and cholesterol-rich membranes such as plasma membranes appear to exist, at least partially, in the liquid-ordered phase or a phase with similar properties. Sphingolipid and cholesterol-rich domains may exist as phase-separated “rafts” in the membrane. We discuss the relationship between detergent-resistant membranes, rafts, caveolae, and low-density plasma membrane fragments. We also discuss possible functions of lipid rafts in membranes. Signal transduction through the high-affinity receptor for IgE on basophils, and possibly through related receptors on other hematopoietic cells, appears to be enhanced by association with rafts. Raft association may also aid in signaling through proteins anchored by glycosylphosphatidylinositol, particularly in hematopoietic cells and neurons. Rafts may also function in sorting and trafficking through the secretory and endocytic pathways.
Proteins of the ADF/Cofilin Family: Essential Regulators of Actin Dynamics
Authors: Bamburg James R.
Published: July 2002

▪ Abstract  Ubiquitous among eukaryotes, the ADF/cofilins are essential proteins responsible for the high turnover rates of actin filaments in vivo. In vertebrates, ADF and cofilin are products of different genes. Both bind to F-actin cooperatively and induce a twist in the actin filament that results in the loss of the phalloidin-binding site. This conformational change may be responsible for the enhancement of the off rate of subunits at the minus end of ADF/cofilin-decorated filaments and for the weak filament-severing activity. Binding of ADF/cofilin is competitive with tropomyosin. Other regulatory mechanisms in animal cells include binding of phosphoinositides, phosphorylation by LIM kinases on a single serine, and changes in pH. Although vertebrate ADF/cofilins contain a nuclear localization sequence, they are usually concentrated in regions containing dynamic actin pools, such as the leading edge of migrating cells and neuronal growth cones. ADF/cofilins are essential for cytokinesis, phagocytosis, fluid phase endocytosis, and other cellular processes dependent upon actin dynamics.
Blue-Light Photoreceptors in Higher Plants
Authors: Briggs Winslow R. , Huala Eva
Published: July 2002

▪ Abstract  In the past few years great progress has been made in identifying and characterizing plant photoreceptors active in the blue/UV-A regions of the spectrum. These photoreceptors include cryptochrome 1 and cryptochrome 2, which are similar in structure and chromophore composition to the prokaryotic DNA photolyases. However, they have a C-terminal extension that is not present in photolyases and lack photolyase activity. They are involved in regulation of cell elongation and in many other processes, including interfacing with circadian rhythms and activating gene transcription. Animal cryptochromes that play a photoreceptor role in circadian rhythms have also been characterized. Phototropin, the protein product of the NPH1 gene in Arabidopsis, likely serves as the photoreceptor for phototropism and appears to have no other role. A plasma membrane protein, it serves as photoreceptor, kinase, and substrate for light-activated phosphorylation. The carotenoid zeaxanthin may serve as the chromophore for a photoreceptor involved in blue-light-activated stomatal opening. The properties of these photoreceptors and some of the downstream events they are known to activate are discussed.
Vertebrate Endoderm Development
Authors: Wells James M. , Melton Douglas A.
Published: July 2002

▪ Abstract  Endoderm, one of the three principal germ layers, contributes to all organs of the alimentary tract. For simplicity, this review divides formation of endodermal organs into four fundamental steps: (a) formation of endoderm during gastrulation, (b) morphogenesis of a gut tube from a sheet of cells, (c) budding of organ domains from the tube, and (d) differentiation of organ-specific cell types within the growing buds. We discuss possible mechanisms that regulate how undifferentiated endoderm becomes specified into a myriad of cell types that populate the respiratory and gastrointestinal tracts.
The Translocon: A Dynamic Gateway at the ER Membrane
Authors: Johnson Arthur E. , van Waes Michael A.
Published: July 2002

▪ Abstract  Cotranslational protein translocation across and integration into the membrane of the endoplasmic reticulum (ER) occur at sites termed translocons. Translocons are composed of several ER membrane proteins that associate to form an aqueous pore through which secretory proteins and lumenal domains of membrane proteins pass from the cytoplasm to the ER lumen. These sites are not passive holes in the bilayer, but instead are quite dynamic both structurally and functionally. Translocons cycle between ribosome-bound and ribosome-free states, and convert between translocation and integration modes of operation. These changes in functional state are accompanied by structural rearrangements that alter translocon conformation, composition, and interactions with ligands such as the ribosome and BiP. Recent studies have revealed that the translocon is a complex and sophisticated molecular machine that regulates the movement of polypeptides through the bilayer, apparently in both directions as well as laterally into the bilayer, all while maintaining the membrane permeability barrier.
Molecular Regulation of Adipogenesis
Authors: Rosen Evan D. , Spiegelman Bruce M.
Published: July 2002

▪ Abstract  Adipogenesis, or the development of fat cells from preadipocytes, has been one of the most intensely studied models of cellular differentiation. In part this has been because of the availability of in vitro models that faithfully recapitulate most of the critical aspects of fat cell formation in vivo. More recently, studies of adipogenesis have proceeded with the hope that manipulation of this process in humans might one day lead to a reduction in the burden of obesity and diabetes. This review explores some of the highlights of a large and burgeoning literature devoted to understanding adipogenesis at the molecular level. The hormonal and transcriptional control of adipogenesis is reviewed, as well as studies on a less well known type of fat cell, the brown adipocyte. Emphasis is placed, where possible, on in vivo studies with the hope that the results discussed may one day shed light on basic questions of cellular growth and differentiation in addition to possible benefits in human health.
Control of Early Seed Development
Authors: Chaudhury Abdul M. , Koltunow Anna , Payne Thomas , Luo Ming , Tucker Mathew R. , Dennis E.S. , Peacock W.J.
Published: July 2002

▪ Abstract  Seed development requires coordinated expression of embryo and endosperm and has contributions from both sporophytic and male and female gametophytic genes. Genetic and molecular analyses in recent years have started to illuminate how products of these multiple genes interact to initiate seed development. Imprinting or differential expression of paternal and maternal genes seems to be involved in controlling seed development, presumably by controlling gene expression in developing endosperm. Epigenetic processes such as chromatin remodeling and DNA methylation affect imprinting of key seed-specific genes; however, the identity of many of these genes remains unknown. The discovery of FIS genes has illuminated control of autonomous endosperm development, a component of apomixis, which is an important developmental and agronomic trait. FIS genes are targets of imprinting, and the genes they control in developing endosperm are also regulated by DNA methylation and chromatin remodeling genes. These results define some exciting future areas of research in seed development.
Peroxisome Biogenesis
Authors: Purdue P. Edward , Lazarow Paul B.
Published: July 2002

▪ Abstract  Fifteen years ago, we had a model of peroxisome biogenesis that involved growth and division of preexisting peroxisomes. Today, thanks to genetically tractable model organisms and Chinese hamster ovary cells, 23 PEX genes have been cloned that encode the machinery (“peroxins”) required to assemble the organelle. Membrane assembly and maintenance requires three of these (peroxins 3, 16, and 19) and may occur without the import of the matrix (lumen) enzymes. Matrix protein import follows a branched pathway of soluble recycling receptors, with one branch for each class of peroxisome targeting sequence (two are well characterized), and a common trunk for all. At least one of these receptors, Pex5p, enters and exits peroxisomes as it functions. Proliferation of the organelle is regulated by Pex11p. Peroxisome biogenesis is remarkably conserved among eukaryotes. A group of fatal, inherited neuropathologies are recognized as peroxisome biogenesis diseases; the responsible genes are orthologs of yeast or Chinese hamster ovary peroxins. Future studies must address the mechanism by which folded, oligomeric enzymes enter the organelle, how the peroxisome divides, and how it segregates at cell division. Most pex mutants contain largely empty membrane “ghosts” of peroxisomes; a few mutants apparently lacking peroxisomes entirely have led some to propose the de novo formation of the organelle. However, there is evidence for residual peroxisome membrane vesicles (“protoperoxisomes”) in some of these, and the preponderance of data supports the continuity of the peroxisome compartment in space and time and between generations of cells.
HYDROLOGICAL MODELING OF CONTINENTAL-SCALE BASINS
Authors: Wood Eric F. , Lettenmaier Dennis , Liang Xu , Nijssen Bart , Wetzel Suzanne W.
Published: July 2002

▪ Abstract  Recent increased interest in the role of the land surface in weather and climate, including impacts due to climate change, has resulted in land surface hydrologic models that incorporate processes which describe the exchange of water and energy at the Earth's surface. The development of a grid-based hydrological model with a full soil-vegetation-atmospheric-transfer (SVAT) land surface parameterization is summarized. The model is suitable both for simulating continental-scale river basins at high temporal and spatial resolutions and as the land surface parameterization in atmospheric general circulation models (AGCMs). Results for the Missouri River basin show the model can successfully simulate hydrological fluxes (e.g. streamflows and evaporation) for large catchments.