bluuebunny/crossref_metadata_2025 huggingface dataset:
SALSA
Authors: Lempel R. , Moran S.
Published: July 2002

Today, when searching for information on the WWW, one usually performs a query through a term-based search engine. These engines return, as the query's result, a list of Web pages whose contents matches the query. For broad-topic queries, such searches often result in a huge set of retrieved documents, many of which are irrelevant to the user. However, much information is contained in the link-structure of the WWW. Information such as which pages are linked to others can be used to augment search algorithms. In this context, Jon Kleinberg introduced the notion of two distinct types of Web pages:
hubs
and
authorities
. Kleinberg argued that hubs and authorities exhibit a
mutually reinforcing relationship
: a good hub will point to many authorities, and a good authority will be pointed at by many hubs. In light of this, he dervised an algoirthm aimed at finding authoritative pages. We present SALSA, a new stochastic approach for link-structure analysis, which examines random walks on graphs derived from the link-structure. We show that both SALSA and Kleinberg's Mutual Reinforcement approach employ the same metaalgorithm. We then prove that SALSA is quivalent to a weighted in degree analysis of the link-sturcutre of WWW subgraphs, making it computationally more efficient than the Mutual reinforcement approach. We compare that results of applying SALSA to the results derived through Kleinberg's approach. These comparisions reveal a topological Phenomenon called the TKC
effect
which, in certain cases, prevents the Mutual reinforcement approach from identifying meaningful authorities.
On the power of one-way communication
Authors: Chang Jik H. , Ibarra Oscar H. , Vergis Anastasios
Published: July 2002

In this paper, a very simple model of parallel computation is considered, and the question of how restricting the flow of data to be one way compares with two-way flow is studied. It is shown that the one-way version is surprisingly very powerful in that it can solve problems that seemingly require two-way communication. Whether or not one-way communication is strictly weaker than two-way is an open problem, although the conjecture in this paper is in the positive. It is shown, however, that proving this conjecture is at least as hard as some well-known open problems in complexity theory.
Shared Vision
Authors: Smith Randall C.
Published: July 2002

General Motors proved fertile ground for implementing collaborative technologies for designing cars.
SchemaSQL
Authors: Lakshmanan Laks V. S. , Sadri Fereidoon , Subramanian Subbu N.
Published: July 2002

We provide a principled extension of SQL, called
SchemaSQL
, that offers the capability of uniform manipulation of data and schema in relational multidatabase systems. We develop a precise syntax and semantics of
SchemaSQL
in a manner that extends traditional SQL syntax and semantics, and demonstrate the following. (1)
SchemaSQL
retains the flavor of SQL while supporting querying of both data and schema. (2) It can be used to transform data in a database in a structure substantially different from original database, in which data and schema may be interchanged. (3) It also permits the creation of views whose schema is dynamically dependent on the contents of the input instance. (4) While aggregation in SQL is restricted to values occurring in one column at a time,
SchemaSQL
permits "horizontal" aggregation and even aggregation over more general "blocks" of information. (5)
SchemaSQL
provides a useful facility for interoperability and data/schema manipulation in relational multidatabase systems. We provide many examples to illustrate our claims. We clearly spell out the formal semantics of
SchemaSQL
that accounts for all these features. We describe an architecture for the implementation of
SchemaSQL
and develop implementation algorithms based on available database technology that allows for powerful integration of SQL based relational DBMS. We also discuss the applicability of
SchemaSQL
for handling semantic heterogeneity arising in a multidatabase system.
Dealing with mobility
Authors: Perry Mark , O'hara Kenton , Sellen Abigail , Brown Barry , Harper Richard
Published: July 2002

The rapid and accelerating move towards use of mobile technologies has increasingly provided people and organizations with the ability to work away from the office and on the move. The new ways of working afforded by these technologies are often characterized in terms of access to information and people anytime, anywhere. This article presents a study of mobile workers that highlights different facets ofaccessto remote people and information, and different facets ofanytime, anywhere. Four key factors in mobile work are identified: the role of planning, working in "dead time," accessing remote technological and informational resources, and monitoring the activities of remote colleagues. By reflecting on these issues, we can better understand the role of technology and artifacts in mobile work and identify the opportunities for the development of appropriate technological solutions to support mobile workers.
A data model for flexible hypertext database systems
Authors: Tompa Frank WM.
Published: July 2002

Hypertext and other page-oriented databases cannot be schematized in the same manner as record-oriented databases. As a result, most hypertext databases implicitly employ a data model based on a simple, unrestricted graph. This paper presents a hypergraph model for maintaining page-oriented databases in such a way that some of the functionality traditionally provided by database schemes can be available to hypertext databases. In particular, the model formalizes identification of commonality in the structure, set-at-a-time database access, and definition of user-specific views. An efficient implementation of the model is also discussed.
Data parallel algorithms
Authors: Hillis W. Daniel , Steele Guy L.
Published: July 2002

Parallel computers with tens of thousands of processors are typically programmed in a data parallel style, as opposed to the control parallel style used in multiprocessing. The success of data parallel algorithms—even on problems that at first glance seem inherently serial—suggests that this style of programming has much wider applicability than was previously thought.
Knowledge and common knowledge in a distributed environment
Authors: Halpern Joseph Y. , Moses Yoram
Published: July 2002

Reasoning about knowledge seems to play a fundamental role in distributed systems. Indeed, such reasoning is a central part of the informal intuitive arguments used in the design of distributed protocols. Communication in a distributed system can be viewed as the act of transforming the system's state of knowledge. This paper presents a general framework for formalizing and reasoning about knowledge in distributed systems. It is shown that states of knowledge of groups of processors are useful concepts for the design and analysis of distributed protocols. In particular,
distributed knowledge
corresponds to knowledge that is “distributed” among the members of the group, while
common knowledge
corresponds to a fact being “publicly known.” The relationship between common knowledge and a variety of desirable actions in a distributed system is illustrated. Furthermore, it is shown that, formally speaking, in practical systems common knowledge cannot be attained. A number of weaker variants of common knowledge that are attainable in many cases of interest are introduced and investigated.
ITS: a tool for rapidly developing interactive applications
Authors: Wiecha Charles , Bennett William , Boies Stephen , Gould John , Greene Sharon
Published: July 2002

The ITS architecture separates applications into four layers. The action layer implements back-end application functions. The dialog layer defines the content of the user interface, independent of its style. Content specifies the objects included in each frame of the interface, the flow of control among frames, and what actions are associated with each object. The style rule layer defines the presentation and behavior of a family of interaction techniques. Finally, the style program layer implements primitive toolkit objects that are composed by the rule layer into complete interaction techniques. This paper describes the architecture in detail, compares it with previous User Interface Management systems and toolkits, and describes how ITS is being used to implement the visitor information system for EXPO '92.
Interactive specification of flexible user interface displays
Authors: Hudson Scott E. , Mohamed Shamim P.
Published: July 2002

One of the problems with conventional UIMSs is that very often there is no graphical way to specify interfaces. This paper describesOPUS, the user interface editor of thePenguimsUIMS. This system allows the presentation component of graphical user interfaces to be specified interactively in a graphical notation without explicit programming. The Penguims UIMS supports an underlying model of computation based loosely on spreadsheets. In particular, it supports incremental computations based on a system of equations (one-way constraints) over a set of named values (spreadsheet cells). These equations are used to provide immediate feedback at all levels of the interface. They are used to incrementally determine the position and dynamic appearance of the individual interactor objects that make up the interface. They are also used to connect the presentation directly to underlying application data thereby supporting semantic feedback. The OPUS user interface editor employs a special graphical notation for specifying the presentation component of a user interface. This notation allows the power of the underlying computational model to be expressed simply and quickly. The resulting presentations are very flexible in nature. They can automatically respond to changes in the size and position of display objects and can directly support derivation of their appearance from application data objects.
LEGAL, ETHICAL, AND SOCIAL ISSUES IN HUMAN GENOME RESEARCH
Authors: Greely Henry T.
Published: July 2002

▪ Abstract  In the past several decades, biological sciences have been revolutionized by their increased understanding of how life works at the molecular level. In what ways, and to what extent, will this scientific revolution affect the human societies within which the science is situated? The legal, ethical, and social implications of research in human genetics have been discussed in depth, particularly in the context of the Human Genome Project and, to a lesser extent, the proposed Human Genome Diversity Project. Both projects could have significant effects on society, the former largely at the level of individuals or families and the latter primarily at the level of ethnic groups or nations. These effects can be grouped in six broad categories: identity, prediction, history, manipulation, ownership and control, and destiny.
Islamic Settlement in North Africa and the Iberian Peninsula
Authors: Boone James L. , Benco Nancy L.
Published: July 2002

▪ Abstract  This article reviews some of the major archeological research and resulting current debates that center around the nature of the formation of Islamic society in the Maghreb and the Iberian Peninsula from the seventh century AD through the later Middle Ages. Over the last two decades, archeology has played an increasingly important role in working out the details of how this great cultural transformation occurred and has led to considerable revision of historical interpretations of the medieval period in the western Mediterranean region. On a more general anthropological level, research in both regions presents a remarkable potential to contribute to the literature on the archeology of ethnicity, and to research into the impact of changing religion and ideology on such diverse areas of human activity as household organization, gender relations, settlement location and spatial organization, and ceramic production and distribution.
THE TIGHT JUNCTION: Morphology to Molecules
Authors: Stevenson Bruce R. , Keon Brigitte H.
Published: July 2002

▪ Abstract  The tight junction forms a regulated barrier in the paracellular pathway between epithelial and endothelial cells. This intercellular junction also demarcates the compositionally distinct apical and basolateral membranes. While the existence of a paracellular barrier in epithelia was hypothesized by physiologists over a century ago, the molecular characterization of the tight junction is a relatively new and rapidly expanding area of research. It is now recognized that the tight junction is comprised of at least nine peripheral and one integral membrane proteins. This complex includes members of a protein family related to tumor suppression and signal transduction, a rab protein, and a Ras target protein. The characteristics of, interactions between, and potential physiological roles of these proteins at the tight junction are discussed.
Interactions of Pathogenic Neisseriae with Epithelial Cell Membranes
Authors: Merz Alexey J. , So Magdalene
Published: July 2002

▪ Abstract  The closely related bacterial pathogens Neisseria gonorrhoeae (gonococci, GC) and N. meningitidis (meningococci, MC) initiate infection at human mucosal epithelia. Colonization begins at apical epithelial surfaces with a multistep adhesion cascade, followed by invasion of the host cell, intracellular persistence, transcytosis, and exit. These activities are modulated by the interaction of a panoply of virulence factors with their cognate host cell receptors, and signals are sent from pathogen to host and host to pathogen at multiple stages of the adhesion cascade. Recent advances place us on the verge of understanding the colonization process at a molecular level of detail. In this review we describe the Neisseria virulence factors in the context of epithelial cell biology, placing special emphasis on the signaling functions of type IV pili, pilus-based twitching motility, and the Opa and Opc outermembrane adhesin/invasin proteins. We also summarize what is known about bacterial intracellular trafficking and growth. With the accelerated integration of tools from cell biology, biochemistry, biophysics, and genomics, experimentation in the next few years should bring unprecedented insights into the interactions of Neisseriae with their host.
Structure and Regulation of Voltage-Gated Ca2+ Channels
Authors: Catterall William A.
Published: July 2002

▪ Abstract  Voltage-gated Ca2+ channels mediate Ca2+ entry into cells in response to membrane depolarization. Electrophysiological studies reveal different Ca2+ currents designated L-, N-, P-, Q-, R-, and T-type. The high-voltage-activated Ca2+ channels that have been characterized biochemically are complexes of a pore-forming α1 subunit of ∼190–250 kDa; a transmembrane, disulfide-linked complex of α2 and δ subunits; an intracellular β subunit; and in some cases a transmembrane γ subunit. Ten α1 subunits, four α2δ complexes, four β subunits, and two γ subunits are known. The Cav1 family of α1 subunits conduct L-type Ca2+ currents, which initiate muscle contraction, endocrine secretion, and gene transcription, and are regulated primarily by second messenger-activated protein phosphorylation pathways. The Cav2 family of α1 subunits conduct N-type, P/Q-type, and R-type Ca2+ currents, which initiate rapid synaptic transmission and are regulated primarily by direct interaction with G proteins and SNARE proteins and secondarily by protein phosphorylation. The Cav3 family of α1 subunits conduct T-type Ca2+ currents, which are activated and inactivated more rapidly and at more negative membrane potentials than other Ca2+ current types. The distinct structures and patterns of regulation of these three families of Ca2+ channels provide a flexible array of Ca2+ entry pathways in response to changes in membrane potential and a range of possibilities for regulation of Ca2+ entry by second messenger pathways and interacting proteins.
Early Eye Development in Vertebrates
Authors: Chow Robert L. , Lang Richard A.
Published: July 2002

▪ Abstract  This review provides a synthesis that combines data from classical experimentation and recent advances in our understanding of early eye development. Emphasis is placed on the events that underlie and direct neural retina formation and lens induction. Understanding these events represents a longstanding problem in developmental biology. Early interest can be attributed to the curiosity generated by the relatively frequent occurrence of disorders such as cyclopia and anophthalmia, in which dramatic changes in eye development are readily observed. However, it was the advent of experimental embryology at the turn of the century that transformed curiosity into active investigation. Pioneered by investigators such as Spemann and Adelmann, these embryological manipulations have left a profound legacy. Questions about early eye development first addressed using tissue manipulations remain topical as we try to understand the molecular basis of this process.
Scaling of Soil Moisture: A Hydrologic Perspective
Authors: Western Andrew W. , Grayson Rodger B. , Blöschl Günter
Published: July 2002

▪ Abstract  Soil moisture is spatially and temporally highly variable, and it influences a range of environmental processes in a nonlinear manner. This leads to scale effects that need to be understood for improved prediction of moisture dependent processes. We provide some introductory material on soil moisture, and then review results from the literature relevant to a variety of scaling techniques applicable to soil moisture. This review concentrates on spatial scaling with brief reference to results on temporal scaling. Scaling techniques are divided into behavioral techniques and process-based techniques. We discuss the statistical distribution of soil moisture, spatial correlation of soil moisture at scales from tens of meters to thousands of kilometers and related interpolation and regularization techniques, and the use of auxiliary variables such as terrain indices. Issues related to spatially distributed deterministic modeling of soil moisture are also briefly reviewed.
MOLECULAR TRANS-SPECIES POLYMORPHISM
Authors: Klein Jan , Sato Akie , Nagl Sandra , O'hUigín Colm
Published: July 2002

▪ Abstract  Trans-species polymorphism (TSP) is the occurrence of similar alleles in related species. Excluding instances in which the similarity arose by convergent evolution, TSP is generated by the passage of alleles from ancestral to descendant species. Closely related, recently diverged species, such as those of the Lake Victoria cichlid flock, may share neutral alleles, but long-lasting TSPs occur only in genetic systems evolving under balancing selection. Two such systems have been studied extensively, the major histocompatibility complex (Mhc) of jawed vertebrates and the self-incompatibility (SI) system of flowering plants. Allelic lineages that diverged many millions of years ago and passed through numerous speciation events have been described in both systems. The lineages may differ at up to 50% of their coding sites, both synonymous and nonsynonymous. The differences arise by the process of incorporation of mutations, which is different from the process of fixation. TSP, on the one hand, complicates phylogenetic analysis, but on the other, it is a useful tool for the study of speciation.
YEAST GENETICS TO DISSECT THE NUCLEAR PORE COMPLEX AND NUCLEOCYTOPLASMIC TRAFFICKING
Authors: Fabre Emmanuelle , Hurt Ed
Published: July 2002

▪ Abstract  Eukaryotic cells evolved when their genetic information was packed into the cell nucleus. DNA replication and RNA biogenesis occur inside the nucleus while protein synthesis takes place in the cytoplasm. Bi-directional trafficking between these two compartments is mediated by a single supramolecular assembly, the nuclear pore complex. Nucleocytoplasmic transport is signal mediated, energy dependent, and requires, besides nuclear pore proteins (nucleoporins), a number of soluble transport factors. We review here our current knowledge on the role of nucleoporins, and on the mechanism of nucleocytoplasmic transport, with emphasis on the yeast Saccharomyces cerevisiae.
ETHICAL ISSUES OF FERTILITY AND REPRODUCTION
Authors: Baird, M.D P. A.
Published: July 2002

▪ Abstract  How reproductive technologies are used has consequences not just for immediate users but for others as well. This article discusses issues that should be taken into consideration in coming to decisions about whether or not it is appropriate to use a particular reproductive technology, or whether to use a technology in a particular way.
DYSTROPHIN-ASSOCIATED PROTEINS AND THE MUSCULAR DYSTROPHIES
Authors: Brown Robert H.
Published: July 2002

▪ Abstract  Discovery of the gene encoding the protein dystrophin delineated not only the cause of Duchenne dystrophy but also an expanding family of at least eight different dystrophin-associated muscle proteins. These include two that span the membrane (the dystroglycans), at least five within the membrane (the sarcoglycans), and a submembrane protein (utrophin). In recent years, defects in the genes for several of these proteins have been identified in several different muscular dystrophies. The spectrum of clinical deficits associated with these genetic lesions is broad, but typically it encompasses both milder proximal myopathies characteristic of limb-girdle dystrophy and more severe disorders reminiscent of Duchenne dystrophy. These discoveries will provide the basis both for improved understanding of physiology of this complex of proteins at the muscle membrane and for new strategies in the treatment of muscular dystrophy.
Sleep and Its Disorders
Authors: Vgontzas, MD A. N. , Kales, MD A.
Published: July 2002

Sleep disorders are very prevalent in the general population and are associated with significant medical, psychological, and social disturbances. Insomnia is the most common. When chronic, it usually reflects psychological/behavioral disturbances. Most insomniacs can be evaluated in an office setting, and a multidimensional approach is recommended, including sleep hygiene measures, psychotherapy, and medication. The parasomnias, including sleepwalking, night terrors, and nightmares, have benign implications in childhood but often reflect psychopathology or significant stress in adolescents and adults and organicity in the elderly. Excessive daytime sleepiness is typically the most frequent complaint and often reflects organic dysfunction. Narcolepsy and idiopathic hypersomnia are chronic brain disorders with an onset at a young age, whereas sleep apnea is more common in middle age and is associated with obesity and cardiovascular problems. Therapeutic naps, medications, and supportive therapy are recommended for narcolepsy and hypersomnia; continuous positive airway pressure, weight loss, surgery, and oral devices are the common treatments for sleep apnea.
Antibody-Targeted Immunotherapy for Treatment of Malignancy
Authors: White Christine A. , Weaver Robin L. , Grillo-López Antonio J.
Published: July 2002

▪ Abstract  Despite testing since the mid-1900s, only in the past three years have some monoclonal antibodies provided sufficient efficacy and safety data to support regulatory approval as cancer therapy. Adjuvant-edrecolomab monoclonal antibody was approved in Germany after demonstration of a statistically significant 32% improvement over observation alone in the seven-year mortality rate for patients with colorectal cancer. Similarly, trastuzumab monoclonal antibody combined with chemotherapy prolonged the median time to the progression of breast cancer compared to chemotherapy alone. Unconjugated monoclonal antibodies investigated for the treatment of hematologic malignancies include anti-idiotype, CAMPATH-1, and rituximab. Rituximab was the first such therapy approved in the United States for relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma after demonstration of an overall response rate of 48% and a duration of response of 11.7 months. The radioisotope-conjugated monoclonal antibodies tested as therapy include anti-B1, LYM-1, LL2, anti-CD33, and ibritumomab tiuxetan. Clearly, the full potential of immunotherapy still lies ahead.
The Role of Inflammation and Infection in Coronary Artery Disease
Authors: Becker Anton E. , de Boer Onno J. , van der Wal Allard C.
Published: July 2002

▪ Abstract  New insights into atherosclerosis, the most common disease affecting coronary arteries, may change therapeutic strategies from largely symptomatic to causal. Atherosclerotic plaques contain a lipid-related, immune-mediated inflammation, with release of secretory products capable of changing plaque morphology. Plaques prone to complications contain large numbers of inflammatory cells; stable plaques contain little inflammation. Similarly, atherectomy specimens from patients with coronary syndromes revealed more inflammatory cells in unstable than in stable patients. These observations, and the fact that acute coronary syndromes are associated with increased blood levels of inflammatory markers, have renewed interest in the possible relationship between infection and atherogenesis. Of all potential candidate antigens, Chlamydia pneumoniae presently is considered the most likely because a substantial number of patients with unstable syndromes contain C. pneumoniae–reactive T cells, both in blood and within the atherosclerotic plaque, suggesting enhancement of intraplaque inflammation.
Bacteriophage Therapy
Authors: Summers William C.
Published: July 2002

▪ Abstract  In 1917, bacteriophages were recognized as epizootic infections of bacteria and were almost immediately deployed for antibacterial therapy and prophylaxis. The early trials of bacteriophage therapy for infectious diseases were confounded, however, because the biological nature of bacteriophage was poorly understood. The early literature reviewed here indicates that there are good reasons to believe that phage therapy can be effective in some circumstances. The advent of antibiotics, together with the “Soviet taint” acquired by phage therapy in the postwar period, resulted in the absence of rigorous evaluations of phage therapy until very recently. Recent laboratory and animal studies, exploiting current understandings of phage biology, suggest that phages may be useful as antibacterial agents in certain conditions.
Human Brain Malformations and Their Lessons for Neuronal Migration
Authors: Ross M Elizabeth , Walsh Christopher A
Published: July 2002

▪ Abstract  The developmental steps required to build a brain have been recognized as a distinctive sequence since the turn of the twentieth century. As marking tools for experimental embryology emerged, the cellular events of cortical histogenesis have been intensively scrutinized. On this rich backdrop, molecular genetics provides the opportunity to play out the molecular programs that orchestrate these cellular events. Genetic studies of human brain malformation have proven a surprising source for finding the molecules that regulate CNS neuronal migration. These studies also serve to relate the significance of genes first identified in murine species to the more complex human brain. The known genetic repertoire that is special to neuronal migration in brain has rapidly expanded over the past five years, making this an appropriate time to take stock of the emerging picture. We do this from the perspective of human brain malformation syndromes, noting both what is now known of their genetic bases and what remains to be discovered.
NUTRITIONAL AND HORMONAL REGULATION OF ENZYMES IN FAT SYNTHESIS: Studies of Fatty Acid Synthase and Mitochondrial Glycerol-3-Phosphate Acyltransferase Gene Transcription
Authors: Sul Hei Sook , Wang Dong
Published: July 2002

▪ Abstract  The activities of critical enzymes in fatty acid and triacylglycerol biosynthesis are tightly controlled by different nutritional, hormonal, and developmental conditions. Feeding previously fasted animals high-carbohydrate, low-fat diets causes a dramatic induction of enzymes—such as fatty acid synthase (FAS) and mitochondrial glycerol-3-phosphate acyltransferase (GPAT)—involved in fatty acid and triacylglycerol synthesis. During fasting and refeeding, transcription of these two enzymes is coordinately regulated by nutrients and hormones, such as glucose, insulin, glucagon, glucocorticoids, and thyroid hormone. Insulin stimulates transcription of the FAS and mitochondrial GPAT genes, and glucagon antagonizes the insulin effect through the cis-acting elements within the promoters and their bound trans-acting factors. This review discusses advances made in the understanding of the transcriptional regulation of FAS and mitochondrial GPAT genes, with emphasis on elucidation of the mechanisms by which multiple nutrients and hormones achieve their effects.
Oligosaccharides in Human Milk: Structural, Functional, and Metabolic Aspects
Authors: Kunz C. , Rudloff S. , Baier W. , Klein N. , Strobel S.
Published: July 2002

Research on human milk oligosaccharides (HMOs) has received much attention in recent years. However, it started about a century ago with the observation that oligosaccharides might be growth factors for a so-called bifidus flora in breast-fed infants and extends to the recent finding of cell adhesion molecules in human milk. The latter are involved in inflammatory events recognizing carbohydrate sequences that also can be found in human milk. The similarities between epithelial cell surface carbohydrates and oligosaccharides in human milk strengthen the idea that specific interactions of those oligosaccharides with pathogenic microorganisms do occur preventing the attachment of microbes to epithelial cells. HMOs may act as soluble receptors for different pathogens, thus increasing the resistance of breast-fed infants. However, we need to know more about the metabolism of oligosaccharides in the gastrointestinal tract. How far are oligosaccharides degraded by intestinal enzymes and does oligosaccharide processing (e.g. degradation, synthesis, and elongation of core structures) occur in intestinal epithelial cells? Further research on HMOs is certainly needed to increase our knowledge of infant nutrition as it is affected by complex oligosaccharides.
STRUCTURE-FUNCTION ASPECTS IN THE NITRIC OXIDE SYNTHASES
Authors: Stuehr Dennis J.
Published: July 2002

▪ Abstract  Research on the biological roles of nitric oxide has revealed that it functions as an important signal and effector molecule in a variety of physiologic and pathologic settings. In animals, nitric oxide is synthesized enzymatically from l-arginine through the actions of the nitric oxide synthases (NOSs). The three known NOS isoforms are all dimeric, bi-domain enzymes that contain iron protoporphyrin IX, flavin adenine dinucleotide, flavin mononucleotide, and tetrahydrobiopterin as bound prosthetic groups. This chapter summarizes information regarding the structure-function aspects of the NOSs, which includes composition of the domains, the protein residues and regions involved in prosthetic group binding, catalytic properties of the domains, the relationship between dimeric structure and prosthetic group binding and function, and factors that control assembly of NOS in cells. A general model for NOS structure and assembly is presented.
FAST PROTEIN DYNAMICS PROBED WITH INFRARED VIBRATIONAL ECHO EXPERIMENTS
Authors: Fayer Michael D
Published: July 2002

▪ Abstract  IR vibrational echo experiments are used to study dynamics in myoglobin (Mb) by investigating the dephasing of the CO-stretching mode of CO bound at the active site of the protein (Mb-CO). The temperature dependence and the viscosity dependence of Mb-CO pure dephasing have been measured in several solvents. In low-temperature, glassy solvents, the pure dephasing has a power law temperature dependence, T1.3, that reflects glasslike protein dynamics. In liquids, the temperature dependence is much steeper and arises from a combination of pure temperature dependence and the influence of decreasing solvent viscosity with increasing temperature. As the solvent viscosity decreases, the ability of the protein's surface to undergo topological fluctuations increases, which in turn increases the internal protein-structural fluctuations. The protein-structural motions are coupled to the CO bound at the active site by electric field fluctuations that accompany movements of polar residues. The dynamic electric field-coupling mechanism is tested by observing differences in the temperature dependence of the pure dephasing of Mb-CO mutations.
EARLY EVENTS IN RNA FOLDING
Authors: Thirumalai D , Lee Namkyung , Woodson Sarah A , Klimov DK
Published: July 2002

▪ Abstract  We describe a conceptual framework for understanding the way large RNA molecules fold based on the notion that their free-energy landscape is rugged. A key prediction of our theory is that RNA folding can be described by the kinetic partitioning mechanism (KPM). According to KPM a small fraction of molecules folds rapidly to the native state whereas the remaining fraction is kinetically trapped in a low free-energy non-native state. This model provides a unified description of the way RNA and proteins fold. Single-molecule experiments on Tetrahymena ribozyme, which directly validate our theory, are analyzed using KPM. We also describe the earliest events that occur on microsecond time scales in RNA folding. These must involve collapse of RNA molecules that are mediated by counterion-condensation. Estimates of time scales for the initial events in RNA folding are provided for the Tetrahymena ribozyme.
Phellinus Weirii and Other Native Root Pathogens as Determinants of Forest Structure and Process in Western North America
Authors: Hansen E.M. , Goheen Ellen Michaels
Published: July 2002

The population structure and ecological roles of the indigenous pathogen Phellinus weirii, cause of laminated root rot in conifer forests of western North America, are examined. This pathogen kills trees in slowly expanding mortality centers, creating gaps in the forest canopy. It is widespread, locally abundant, and very long-lived. It is among the most important disturbance agents in the long intervals between stand-replacing events such as wildfire or harvest in these ecosystems and shapes the structure and composition of both wild and managed forests. Trees are infected and killed regardless of individual vigor. Management of public lands is changing dramatically, with renewed emphasis on natural forest structures and processes but pathogens, especially root rot fungi, remain a significant challenge to “ecosystem management.”
DOES DEMOCRACY CAUSE PEACE?
Authors: Ray James Lee
Published: July 2002

▪ Abstract  The idea that democratic states have not fought and are not likely to fight interstate wars against each other runs counter to the realist and neorealist theoretical traditions that have dominated the field of international politics. Since the mid-1970s, the generation of new data and the development of superior analytical techniques have enabled evaluators of the idea to generate impressive empirical evidence in favor of the democratic peace proposition, which is reinforced by substantial theoretical elaboration. Some critics argue that common interests during the Cold War have been primarily responsible for peace among democracies, but both statistical evidence and intuitive arguments cast doubt on that contention. It has also been argued that transitions to democracy can make states war-prone, but that criticism too has been responded to persuasively. The diverse empirical evidence and developing theoretical bases that support the democratic peace proposition warrant confidence in its validity.
Constructing Effective Environmental Regimes
Authors: Downs George W.
Published: July 2002

In the environmental literature, accounts of cooperative progress commonly emphasize the activity and leadership of nongovernmental organizations, as well as the constitutive roles that environmental regimes play by legitimizing, by promoting reflectivist discourse, and by redefining roles. This essay lays out the differences between the constructivist and political-economic theories of environmental regime effectiveness and examines the extent to which the constructivist emphasis is empirically justified by three recent collections of case studies. Of the surprisingly modest effects that environmental regimes have had, most appear to have come through the use of mechanisms that already play a prominent role in the political economy literature. Constructivist processes, despite the attention they have received, appear to have had only a marginal impact.
THE PUBLIC HEALTH ASPECTS OF COMPLEX EMERGENCIES AND REFUGEE SITUATIONS
Authors: Toole MJ , Waldman RJ
Published: July 2002

▪ Abstract  Populations affected by armed conflict have experienced severe public health consequences mediated by population displacement, food scarcity, and the collapse of basic health services, giving rise to the term complex humanitarian emergencies. These public health effects have been most severe in underdeveloped countries in Africa, Asia, and Latin America. Refugees and internally displaced persons have experienced high mortality rates during the period immediately following their migration. In Africa, crude mortality rates have been as high as 80 times baseline rates. The most common causes of death have been diarrheal diseases, measles, acute respiratory infections, and malaria. High prevalences of acute malnutrition have contributed to high case fatality rates. In conflict-affected European countries, such as the former Yugoslavia, Georgia, Azerbaijan, and Chechnya, war-related injuries have been the most common cause of death among civilian populations; however, increased incidence of communicable diseases, neonatal health problems, and nutritional deficiencies (especially among the elderly) have been documented. The most effective measures to prevent mortality and morbidity in complex emergencies include protection from violence; the provision of adequate food rations, clean water and sanitation; diarrheal disease control; measles immunization; maternal and child health care, including the case management of common endemic communicable diseases; and selective feeding programs, when indicated.
Nutrition, Genetics, and Risks of Cancer
Authors: Rock Cheryl L. , Lampe Johanna W. , Patterson Ruth E.
Published: July 2002

▪ Abstract  Dietary patterns, nutrients, and other constituents of food are major components of the environmental influences that contribute to risk for cancer, and the study of interactions between nutritional and genetic factors is a new and important area of research. This review describes the concepts and principles underlying this area of study and types of relationships between nutritional and genetic factors, and it provides examples of specific diet-gene interactions that are of current interest, with an emphasis on implications for cancer prevention and public health. Polymorphisms exist in the genes for the activating and conjugating metabolizing enzymes, and the induction of metabolizing enzyme activity by nutritional factors may result in either the activation of a carcinogen or the detoxification of a reactive intermediate metabolite. The relationship between the methylenetetrahydrofolate reductase gene and dietary folate is an example of a diet-gene interaction that involves a polymorphism in a vitamin metabolism gene, and the presence of the variant appears to influence both risk for cancer and folate requirements. Diet-gene interactions likely contribute considerably to the observed inter-individual variations in cancer risk in response to exposures to the nutritional factors that have the potential to promote or protect against cancer. Insights into mechanisms by which nutritional factors affect the process of carcinogenesis are provided by knowledge of the targeted gene function and enzyme activity. Increased knowledge in this area will allow a more refined approach to reducing risk for cancer, with diet interventions targeted toward individuals and subgroups that are genetically susceptible and responsive to the effects of nutritional factors.

Investigating the cellular and molecular pathogenesis of cancer is an established and important area of basic science research. Within the past several years, the capability of examining biomarkers of various genetic factors in the development and progression of chronic diseases, such as cancers, has enabled researchers to study these factors in clinical and community-based populations, in which environmental factors can also be measured or even manipulated. Dietary patterns and the nutrients and other co nstituents of food are a major component of the environmental influen ces that appear to contribute to disease risk, and the study of interactions between nutritional and genetic factors is a new and important area of research. This review describes the concepts and principles underlying this area of study, describes types of relationships between nutritional and genetic factors, provides examples of specific diet-gene interactions that are of current interest, and comments on implications for cancer prevention and public health.
Globalization and Democracy
Authors: Schwartzman Kathleen C.
Published: July 2002

By 1996, 66% of the countries of the world were using elections to choose their top leaders. This wave of democratization was accompanied by a paradigm shift that took the large number of historically clustered democratizations and called it a “wave.” The scholarship has moved beyond overly episodic, event-oriented accounts of democratization to comparative work that investigates the impact of global processes on the political regimes of nations. This review examines numerous renderings of the linkage between globalization and democratization, including: favorable climate for democracy, global economic growth, global crises, foreign intervention, hegemonic shifts, and world-system contraction. Those authors who have advanced a stronger theoretical integration of the global and domestic processes offer exceptional insight into the momentous shifts that recently have occurred.
Using Computers to Analyze Ethnographic Field Data: Theoretical and Practical Considerations
Authors: Dohan Daniel , Sánchez-Jankowski Martín
Published: July 2002

Computer-assisted data analysis is usually associated with the analysis of aggregate data according to the tenets of logical positivism. But there are more than twenty computer programs designed to assist researchers analyzing ethnographic data, and these programs may be used by researchers with a variety of epistemological orientations. Some computer-assisted qualitative data analysis (CAQDA) programs automate analysis procedures that have been used by generations of ethnographers. Others open up new directions through the use of linked coding schemes, hypertext, and case-based hypothesis testing. Ethnographers interested in computer assistance must acquaint themselves with the variety of capabilities and programs available because no one program dominates the CAQDA field. In this article, we provide an overview of the theoretical and practical considerations bearing on the choice of CAQDA software.
Feminist State Theory: Applications to Jurisprudence, Criminology, and the Welfare State
Authors: Haney Lynne A.
Published: July 2002

This chapter discusses developments in feminist state theory through a comparison of feminist interventions into jurisprudence, criminology, and welfare state theory. Early feminist work on the state analyzed how women were subordinated by a centralized state. More recently, feminist scholars unearthed how states are differentiated entities, comprised of multiple gender arrangements. This discovery of state variation surfaced differently in these three branches of scholarship. Feminist legal theorists concentrated on multiple legal discourses, feminist criminologists on the diverse sites of case processing, and feminist welfare theorists on the varied dimensions of welfare stratification. Because of their different approaches to state gender regimes, these scholars have much to offer, and to gain from, one another. Thus, this chapter argues for the importance of an interdisciplinary feminist dialogue on the state. It also suggests ways to promote such a dialogue and to insert a sociological perspective into this new mode of theorizing.
Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart Failure
Authors: Doehner Wolfram , Schoene Nina , Rauchhaus Mathias , Leyva-Leon Francisco , Pavitt Darrell V. , Reaveley David A. , Schuler Gerhard , Coats Andrew J.S. , Anker Stefan D. , Hambrecht Rainer
Published: July 2002

Background
—

In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)–derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies.

Methods and Results
—

In 10 CHF patients with normal serum uric acid (UA) levels (315±42 μmol/L) and 9 patients with elevated UA (535±54 μmol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 μg/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients (
P
<0.05). In a double-blind, crossover design, hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558±21 μmol/L, range 455 to 743 μmol/L), treatment reduced UA by >120 μmol/L in all patients (mean reduction 217±15 μmol/L,
P
<0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (+24%,
P
=0.027) and legs (+23%,
P
=0.029). Flow-dependent flow improved by 58% in arms (
P
=0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment (
P
<0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment (
r
=0.63,
P
<0.05).

Conclusions
—

In hyperuricemic CHF patients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.