bluuebunny/crossref_metadata_2025 huggingface dataset:
Operator work load: when is enough enough?
Authors: LeMay Moira , Hird Eric
Published: July 2002

Three measures of operator mental work load were tested with a large, interactive computer system. Two—operator rating of time stress, and the ratio of the time required to time allowed for each subtask—proved to be significant and easy to use.
System structure and software maintenance performance
Authors: Gibson Virginia R. , Senn James A.
Published: July 2002

An experiment is designed to investigate the relationship between system structure and maintainability. An old, ill-structured system is improved in two sequential stages, yielding three system versions for the study. The primary objectives of the research are to determine how or whether the differences in the systems influence maintenance performance; whether the differences are discernible to programmers; and whether the differences are measurable. Experienced programmers perform a portfolio of maintenance tasks on the systems. Results indicate that system improvements lead to decreased total maintenance time and decreased frequency of ripple effect errors. This suggests that improving old systems may be worthwhile and may yield benefits over the remaining life of the system. System differences are not discernible to programmers; apparently programmers are unable to separate the complexity of the systems from the complexity of the maintenance tasks. This finding suggests a need for further research on the efficacy of subjectively based software metrics. Finally, results indicate that a selected set of automatable, objective complexity metrics reflected both the improvements in the system and programmer maintenance performance. These metrics appear to offer potential as project management tools.
Finding all isolated solutions to polynomial systems using HOMPACK
Authors: Morgan Alexander P. , Sommese Andrew J. , Watson Layne T.
Published: July 2002

Although the theory of polynomial continuation has been established for over a decade (following the work of Garcia, Zangwill, and Drexler), it is difficult to solve polynomial systems using continuation in practice. Divergent paths (solutions at infinity), singular solutions, and extreme scaling of coefficients can create catastrophic numerical problems. Further, the large number of paths that typically arise can be discouraging. In this paper we summarize polynomial-solving homotopy continuation and report on the performance of three standard path-tracking algorithms (as implemented in HOMPACK) in solving three physical problems of varying degrees of difficulty. Our purpose is to provide useful information on solving polynomial systems, including specific guidelines for homotopy construction and parameter settings. The
m
-homogeneous strategy for constructing polynomial homotopies is outlined, along with more traditional approaches. Computational comparisons are included to illustrate and contrast the major HOMPACK options. The conclusions summarize our numerical experience and discuss areas for future research.
Knowledge-based search tactics for an intelligent intermediary system
Authors: Smith Philip J. , Shute Steven J. , Galdes Beb , Chignell Mark H.
Published: July 2002

Research on the nature of knowledge-based systems for bibliographic information retrieval is summarized. Knowledge-based search tactics are then considered in terms of their role in the functioning of a semantically based search system for bibliographic information retrieval, EP-X. This system uses such tactics to actively assist users in defining or refining their topics of interest. It does so by applying these tactics to a knowledge base describing topics in a particular domain and to a database describing the contents of individual documents in terms of these topics. This paper, then, focuses on the two central concepts behind EP-X: semantically based search and knowledge-based search tactics.
CASE productivity perceptions of software engineering professionals
Authors: Norman Ronald J. , Nunamaker Jay F.
Published: July 2002

Computer-aided software engineering (CASE) is moving into the problem-solving domain of the systems analyst. The authors undertook a study to investigate the various functional and behavioral aspects of CASE and determine the impact it has over manual methods of software engineering productivity.
A fast adaptive grid scheme for elliptic partial differential equations
Authors: Ribbens Calvin J.
Published: July 2002

We describe the Recursive Subdivision (RS) method-an efficient and effective adaptive grid scheme for two-dimensional elliptic partial differential equations (PDEs). The RS method generates a new grid by recursively subdividing a rectangular domain. We use a heuristic approach which attempts to equidistribute a given density function over the domain. The resulting grid is used to generate an adaptive grid domain mapping (AGDM), which may be applied to transform the PDE problem to another coordinate system. The PDE is then solved in the transformed coordinate system using a uniform grid. We believe parallelism is most easily exploited when computations are carried out on uniform grids; the AGDM framework allows the power of adaptation to be applied while still preserving this uniformity. Our method generates good adaptive grid domain mappings at a small cost compared to the cost of the entire computation. We describe the RS algorithm in detail, briefly describe the AGDM framework, and illustrate the effectiveness of our scheme on several realistic test problems.
User cube: a taxonomy of end users
Authors: Cotterman William W. , Kumar Kuldeep
Published: July 2002

The user cube, a precise and comprehensive graphical taxonomy designed to provide a common base for understanding and classifying end users in organizations, can be used to assess the risks associated with end-user computing.
Security-control methods for statistical databases: a comparative study
Authors: Adam Nabil R. , Worthmann John C.
Published: July 2002

This paper considers the problem of providing security to statistical databases against disclosure of confidential information. Security-control methods suggested in the literature are classified into four general approaches: conceptual, query restriction, data perturbation, and output perturbation.

Criteria for evaluating the performance of the various security-control methods are identified. Security-control methods that are based on each of the four approaches are discussed, together with their performance with respect to the identified evaluation criteria. A detailed comparative analysis of the most promising methods for protecting dynamic-online statistical databases is also presented.

To date no single security-control method prevents both exact and partial disclosures. There are, however, a few perturbation-based methods that prevent exact disclosure and enable the database administrator to exercise "statistical disclosure control." Some of these methods, however introduce bias into query responses or suffer from the 0/1 query-set-size problem (i.e., partial disclosure is possible in case of null query set or a query set of size 1).

We recommend directing future research efforts toward developing new methods that prevent exact disclosure and provide statistical-disclosure control, while at the same time do not suffer from the bias problem and the 0/1 query-set-size problem. Furthermore, efforts directed toward developing a bias-correction mechanism and solving the general problem of small query-set-size would help salvage a few of the current perturbation-based methods.
Faster algorithms for the shortest path problem
Authors: Ahuja Ravindra K. , Mehlhorn Kurt , Orlin James , Tarjan Robert E.
Published: July 2002

Efficient implementations of Dijkstra's shortest path algorithm are investigated. A new data structure, called the
radix heap
, is proposed for use in this algorithm. On a network with
n
vertices,
m
edges, and nonnegative integer arc costs bounded by
C
, a one-level form of radix heap gives a time bound for Dijkstra's algorithm of
O
(
m
+
n
log
C
). A two-level form of radix heap gives a bound of
O
(
m
+
n
log
C
/log log
C
). A combination of a radix heap and a previously known data structure called a
Fibonacci heap
gives a bound of
O
(
m
+
n
a @@@@log
C
). The best previously known bounds are
O
(
m
+
n
log
n
) using Fibonacci heaps alone and
O
(
m
log log
C
) using the priority queue structure of Van Emde Boas et al. [ 17].
The RGYB color geometry
Authors: Ware Colin , Cowan William
Published: July 2002

Background:

The gamut of a color CRT is defined by its three primary colors, each produced by a phosphor/electron gun combination. Light from the primaries combines additively, so the color gamut is a subset of a three dimensional vector space [1]. With the primaries as basis vectors normalized to 1.0, the color gamut is a unit cube, known as the RGB color geometry, since the three primaries are usually red, green, and blue. User interaction via RGB is generally thought to be counterintuitive, and transformations of RGB, such as Smith's HSV geometry [10] which is derived from centuries old artists' models [2], are more popular. More recent color theories, based on psychophysical and physiological models of early visual processing, suggest that more intuitive geometries may be possible.

The RGYB geometry is based on two recent discoveries about the human visual system. First, the three color signals from the cone receptors are organized into three opponent channels [1, 7]. A single achromatic channel indicates lightness or brightness. Two chromatic channels, red/green and yellow/blue, signal the chromatic quantities. Second, signals on the achromatic channel are easily distinguishable from signals on the chromatic ones [6]. Consequently, it is usual to represent colors as a set of surfaces of colors that vary in chromaticity, each at a different level of brightness. Examples are as diverse as CIE chromaticity coordinates, the CIELUV uniform color space, the Munsell color system, and computer graphics color spaces such as HSV and HLS [10, 12].
Surveying current research in object-oriented design
Authors: Wirfs-Brock Rebecca J. , Johnson Ralph E.
Published: July 2002

The state of object-oriented is evolving rapidly. This survey describes what are currently thought to be the key ideas. Although it is necessarily incomplete, it contains both academic and industrial efforts and describes work in both the United States and Europe. It ignores well-known ideas, like that of Coad and Meyer [34], in favor of less widely known projects.

Research in object-oriented design can be divided many ways. Some research is focused on describing a design process. Some is focused on finding rules for good designs. A third approach is to build tools to support design. Most of the research described in this article does all three.

We first present work from Alan Snyder at Hewlett-Packard on developing a common framework for object-oriented terminology. The goal of this effort is to develop and communicate a corporate-wide common language for specifying and communicating about objects.

We next look into the research activity at Hewlett-Packard, led by Dennis de Champeaux. De Champeaux is developing a model for object-based analysis. His current research focuses on the use of a trigger-based model for inter-object communications and development of a top-down approach to analysis using ensembles.

We then survey two research activities that prescribe the design process. Rebecca Wirfs-Brock from Tektronix has been developing an object-oriented design method that focuses on object responsibilities and collaborations. The method includes graphical tools for improving encapsulation and understanding patterns of object communication. Trygve Reenskaug at the Center for Industriforskning in Oslo, Norway has been developing an object-oriented design method that focuses on roles, synthesis, and structuring. The method, called Object-Oriented Role Analysis, Syntheses and Structuring, is based on first modeling small sub-problems, and then combining small models into larger ones in a controlled manner using both inheritance (synthesis) and run-time binding (structuring).

We then present investigations by Ralph Johnson at the University of Illinois at Urbana-Champaign into object-oriented frameworks and the reuse of large-scale designs. A framework is a high-level design or application architecture and consists of a suite of classes that are specifically designed to be refined and used as a group. Past work has focused on describing frameworks and how they are developed. Current work includes the design of tools to make it easier to design frameworks.

Finally, we present some results from the research group in object-oriented software engineering at Northeastern University, led by Karl Lieberherr. They have been working on object-oriented Computer Assisted Software Engineering (CASE) technology, called the Demeterm system, which generates language-specific class definitions from language-independent class dictionaries. The Demeter system include tools for checking design rules and for implementing a design.
SIMULATIONS OF STRUCTURE FORMATION IN THE UNIVERSE
Authors: Bertschinger Edmund
Published: July 2002

▪ Abstract  Cosmic structure has formed as a result of gravitational amplification of primordial density fluctuations together with the action of other physical processes (adiabatic gas dynamics, radiative cooling, photoionization and recombination, radiative transfer). These complex nonlinear processes, acting over a wide range of length scales (from kiloparsecs to tens of megaparsecs), make this a difficult problem for computation. During the last two decades, significant progress has been made in developing numerical methods and statistical tools for analyzing simulations and data. Combined with observational advances, numerical simulations have led to the demise of several formerly popular models and to an improved understanding of galaxy clusters, quasistellar object (QSO) absorption line systems, and other phenomena. This review summarizes these advances.
HERPES SIMPLEX VIRUS DNA REPLICATION
Authors: Boehmer Paul E. , Lehman I. R.
Published: July 2002

The Herpesviridae comprise a large class of animal viruses of considerable public health importance. Of the Herpesviridae, replication of herpes simplex virus type-1 (HSV-1) has been the most extensively studied. The linear 152-kbp HSV-1 genome contains three origins of DNA replication and approximately 75 open-reading frames. Of these frames, seven encode proteins that are required for origin-specific DNA replication. These proteins include a processive heterodimeric DNA polymerase, a single-strand DNA-binding protein, a heterotrimeric primosome with 5′-3′ DNA helicase and primase activities, and an origin-binding protein with 3′-5′ DNA helicase activity. HSV-1 also encodes a set of enzymes involved in nucleotide metabolism that are not required for viral replication in cultured cells. These enzymes include a deoxyuridine triphosphatase, a ribonucleotide reductase, a thymidine kinase, an alkaline endo-exonuclease, and a uracil-DNA glycosylase. Host enzymes, notably DNA polymerase α-primase, DNA ligase I, and topoisomerase II, are probably also required.

Following circularization of the linear viral genome, DNA replication very likely proceeds in two phases: an initial phase of theta replication, initiated at one or more of the origins, followed by a rolling-circle mode of replication. The latter generates concatemers that are cleaved and packaged into infectious viral particles. The rolling-circle phase of HSV-1 DNA replication has been reconstituted in vitro by a complex containing several of the HSV-1 encoded DNA replication enzymes. Reconstitution of the theta phase has thus far eluded workers in the field and remains a challenge for the future.
Visual Prostheses
Authors: Maynard Edwin M.
Published: July 2002

▪ Abstract  The development of man-made systems to restore functional vision in the profoundly blind has recently undergone a renaissance that has been fueled by a combination of celebrity and government interest, advances in the field of bioengineering, and successes with existing neuroprosthetic systems. This chapter presents the underlying physiologic principles of artificial vision, discusses three contemporary approaches to restoring functional vision in the blind, and concludes by presenting several relevant questions to vision prostheses. While there has been significant progress in the individual components constituting an artificial vision system, the remaining challenge of integrating these components with each other and the nervous system does not lie strictly in the realm of neuroscience, medicine, or engineering but at the interface of all three. In spite of the apparent complexity of an artificial vision system, it is not unreasonable to be optimistic about its eventual success.
STRUCTURE-FUNCTION ANALYSIS OF THE MOTOR DOMAIN OF MYOSIN
Authors: Ruppel Kathleen M. , Spudich James A.
Published: July 2002

▪ Abstract  Motor proteins perform a wide variety of functions in all eukaryotic cells. Recent advances in the structural and mutagenic analysis of the myosin motor has led to insights into how these motors transduce chemical energy into mechanical work. This review focuses on the analysis of the effects of myosin mutations from a variety of organisms on the in vivo and in vitro properties of this ubiquitous motor and illustrates the positions of these mutations on the high-resolution three-dimensional structure of the myosin motor domain.
Implications of Extrasolar Planets for Understanding Planet Formation
Authors: Bodenheimer Peter , Lin D.N.C.
Published: July 2002

▪ Abstract  The observed properties of extrasolar planets and planetary systems are reviewed, including discussion of the mass, period, and eccentricity distributions; the presence of multiple systems; and the properties of the host stars. In all cases, the data refer to systems with ages in the Ga range. Some of the properties primarily reflect the formation mechanism, while others are determined by postformation dynamical evolutionary processes. The problem addressed here is the extraction of information relevant to the identification of the formation mechanism. The presumed formation sites, namely disks around young stars, therefore, must provide clues at times much closer to the actual formation time. The properties of such disks are briefly reviewed. The amount of material and its distribution in the disks provide a framework for the development of a model for planet formation. The strengths of, as well as the problems with, the two major planet formation mechanisms—gravitational instability and core accretion–gas capture—are then described. It is concluded that most of the known planetary systems are best explained by the accretion process. The timescales for the persistence of disks and for the formation time by this process are similar, and the mass range of the observed planets, up to approximately 10 Jupiter masses, is naturally explained. The mass range of 5–15 Jupiter masses probably represents an overlapping transition region, with planetary formation processes dominating below that range and star formation processes dominating above it.
NUCLEAR ENERGY IN THE TWENTY-FIRST CENTURY: Examination of a Contentious Subject
Authors: Beck Peter W.
Published: July 2002

▪ Abstract  The worldwide future of nuclear energy is a highly disputed subject; one side is certain that nuclear energy will have to expand in the next century to meet energy demand, whereas the other side is equally certain that this energy form is too dangerous and uneconomical to be of longer-term use. By looking at the way such beliefs are formed, the history of nuclear power, and the energy scene in the next century, this paper tests both points of view and concludes that both are flawed, but there is a strong case for keeping the option for nuclear expansion open. Yet, there has to be doubt whether today's technology is adequate for such expansion. There are alternative technologies under development that may make nuclear power more acceptable; however, although there is the time to develop such new processes, the question has to be asked whether such work can be funded, unless public opposition to nuclear power can be reduced and international collaboration improved. The long-term future of nuclear power depends more on successful research and development than on achieving early orders for more nuclear plants.
THEECONOMICS OF“WHEN” FLEXIBILITY IN THEDESIGN OFGREENHOUSEGASABATEMENTPOLICIES
Authors: Toman Michael A. , Morgenstern Richard D. , Anderson John
Published: July 2002

▪ Abstract  This paper focuses on the desirability, from an economic perspective, of setting fixed and relatively short-term targets and timetables, such as those contained in the Kyoto Protocol, as a means of achieving longer-term climate change mitigation goals. The paper argues that whatever long-term policy goals are adopted, greater flexibility lowers implementation costs. Lower implementation costs, in turn, increases the likelihood that the policies will actually be followed and the goals achieved. Importantly, the Kyoto Protocol incorporates key elements of both “what” and “where” flexibility. That is, the “Kyoto basket” includes all six of the major greenhouse gases plus sinks, and the Protocol incorporates several mechanisms that allow emission reductions to take place at the least-cost geographic location, regardless of nation-state boundaries. The Protocol also provides substantial “how” flexibility in the sense that countries can use a variety of means to achieve domestic policy goals. However, the Protocol does not allow emission reductions to take place at a point in time when they can be achieved at lowest cost as long as they are consistent with the long-term environmental goals (“when” flexibility). Additionally, it does not allow the use of efficient price-based policy instruments to define targets and, thereby, balance environmental goals and compliance costs (which could be thought of as a broader version of “when” flexibility). Instead, the Protocol relies exclusively on strict, short term quantity targets. The relative inflexibility of the Protocol with respect to the timing of reductions and definitions of the targets may derive, in part, from a misplaced analogy between the global warming issue and the highly successful effort to phase out CFCs under the Montreal Protocol. The lack of when flexibility may be a key barrier to achieving the broader goals of the Kyoto Protocol, particularly if where flexibility is constrained in the implementation process.
INTERIM STORAGE OF SPENT FUEL IN THE UNITED STATES
Authors: Macfarlane Allison
Published: July 2002

▪ Abstract  At nuclear power reactors around the United States, quantities of spent or irradiated nuclear fuel are growing while owner-operator companies await the approval of a permanent storage facility. Some reactors have run out of space in their cooling pools and have had to resort to dry cask storage. The first half of this paper looks at the policy history of interim storage in the United States, discusses the current storage status at individual reactors, and then reviews the technologies available to deal with it. The second half of the paper considers the different options for dealing with this hazardous material in the interim, before a permanent high-level nuclear waste repository is opened, and examines the safety, security, transportation, economic, political, and other issues that bear on the choice of option.
GENETIC MODELS OF OBESITY AND ENERGY BALANCE IN THE MOUSE
Authors: Robinson Susan W , Dinulescu Daniela M , Cone Roger D
Published: July 2002

▪ Abstract  Obesity is a health problem of epidemic proportions in the industrialized world. The cloning and characterization of the genes for the five naturally occurring monogenic obesity syndromes in the mouse have led to major breakthroughs in understanding the physiology of energy balance and the contribution of genetics to obesity in the human population. However, the regulation of energy balance is an extremely complex process, and it is quickly becoming clear that hundreds of genes are involved. In this article, we review the naturally occurring monogenic and polygenic obese mouse strains, as well as the large number of transgenic and knockout mouse models currently available for the study of obesity and energy balance.
BONE MARROW–DERIVED DENDRITIC CELLS, INFECTION WITH HUMAN IMMUNODEFICIENCY VIRUS, AND IMMUNOPATHOLOGY
Authors: Knight Stella C. , Patterson Steven
Published: July 2002

▪ Abstract  Dendritic cells (DC) exposed to HIV-1 show nonproductive infection that may become productive as they mature. The distribution of DC within genital mucosa and their susceptibility to infection particularly with clade E viruses could be reflected in the ease of heterosexual transmission. Carriage of virus and viral antigen by DC into lymph nodes may allow clustering and activation of T cells and production of protective immune responses. However, secondary infection of activated T cells from infected DC could cause dissemination of virus and loss of infected DC and T cells. In asymptomatic infection, fewer dendritic cells with reduced capacity to stimulate CD4 T cell proliferation are found before evidence of T cell abnormalities, and these early changes in antigen-presenting cells may result in a decline in the production of CD4 memory T cells. However, DC fuel ongoing production of antibody to HIV-1. Signaling by DC to T cells may thus underlie two major features of early HIV infection—loss in CD4+memory T cells and persistence of antibody production. In AIDS, infected dendritic and epithelial cells within the thymus may affect maturation and contribute to loss of the “naive” T cell population. Further loss of memory T cells may occur through syncytium formation with infected DC. Finally, in AIDS patients, there is a failure in the development and the function of DC from CD34+stem cells. In conclusion, the infection of dendritic cells, loss in their numbers, and changed signaling to T cells may shape the pattern of immunity during infection with HIV-1. Conversely, treatments that reverse the defect in antigen presentation by DC may improve cell-mediated immunity.
A Trip Through my Life With an Immunological Theme
Authors: Janeway Charles A.
Published: July 2002

In this essay, I make four points about the operation of the immune system. First, thanks to the innate immune system's regulation of the main costimulatory molecules CD80 and CD86, the immune system rarely mistakes a pathogen for a self-antigen. Second, the adaptive immune system consisting of T lymphocytes and B lymphocytes can mistake self for non-self because adaptive immunity is selected in single somatic cells. Third, the adaptive immune system of T lymphocytes and B lymphocytes is always referential to self, as it is selected on self-ligands; it persists in the periphery on self-ligands; and at least for T cells, it is dependent on self-ligands to be able to mount a response. Fourth, it is becoming clear that regulatory or suppressor T cells are our main defense against autoimmunity, as my first boss, Richard Gershon, had predicted. These cells recognize antigen as do all T cells, but they secrete the immunoregulatory cytokines IL-10 and TGFβ.
NOVEL ANTITHROMBOTIC THERAPEUTICS TARGETED AGAINST PLATELET GLYCOPROTEIN IIb/IIIa
Authors: Coutré, M.D Steven , Leung, M.D Lawrence
Published: July 2002

▪ Abstract  Platelet aggregation is one of the best understood examples of adhesive cell-cell interactions. The platelet glycoprotein IIb/IIIa membrane receptor plays a pivotal role in platelet aggregation through its binding of fibrinogen. It is intimately involved in the pathogenesis of platelet-rich arterial thromboses. The IIb/IIIa receptor is an important target for recently described novel antiplatelet therapeutics. The development and clinical evaluation of this class of antiplatelet therapeutics are reviewed in this article.
HOW DOES LITHIUM WORK ON MANIC DEPRESSION? Clinical and Psychological Correlates of the Inositol Theory
Authors: Belmaker, M.D R. H. , Bersudsky, M.D Yuly , Agam, M.D Galila , Levine, M.D Joseph , Kofman, M.D Ora
Published: July 2002

▪ Abstract  How lithium works in manic-depressive illness is unknown. Recently, however, a powerful hypothesis has been gaining momentum. Distinguished by its testability and clinical implications, the inositol depletion hypothesis of lithium action is relevant to treatment of lithium side effects, to the development of new compounds with the clinical profile of lithium, and to new experimental treatment of depression.
ENDOCRINE TUMORS OF THE GASTROINTESTINAL TRACT
Authors: Perry Roger R. , Vinik Aaron I.
Published: July 2002

▪ Abstract  Endocrine tumors of the gastrointestinal tract produce a variety of secretory products that cause unique clinical syndromes. Diagnosis, which is often delayed, requires a strong index of suspicion and must be confirmed by biochemical tests. Precisely where these tumors originate remains a topic of controversy. However, several growth factors that may be involved in tumor development have been identified, and genetic abnormalities in patients with multiple endocrine neoplasia have been described. New pre- and intraoperative localization techniques have greatly increased the ability to identify and resect these tumors. The long-acting somatostatin analogue octreotide is frequently useful as a tracer to localize tumors and as symptomatic therapy for limiting release of secretory products produced by the tumors. In some instances it may also have direct anti-tumor activity.
Hereditary Peripheral Neuropathies: Clinical Forms, Genetics, and Molecular Mechanisms
Authors: Warner Laura E. , Garcia, MD Carlos A. , Lupski, MD, PhD James R.
Published: July 2002

Hereditary peripheral neuropathies, among the most common genetic disorders in humans, are a complex, clinically and genetically heterogeneous group of disorders that produce progressive deterioration of the peripheral nerves. This group of disorders includes hereditary neuropathy with liability to pressure palsies, Charcot-Marie-Tooth disease, Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy. Our understanding of these disorders has progressed from the description of the clinical phenotypes and delineation of the electrophysiologic and pathologic features to the identification of disease genes and elucidation of the underlying molecular mechanisms.
Allergic Bronchopulmonary Aspergillosis
Authors: Cockrill, MD B. A. , Hales, MD C. A.
Published: July 2002

Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome seen in patients with asthma and cystic fibrosis. It is characterized by chronic colonization of the airways with a ubiquitous fungus, Aspergillus fumigatus. The clinical expression of ABPA results from the complex interaction of chronic colonization of the airways with A. fumigatus, host factors allowing this colonization, and the host's genetically determined immune response. Clinically the syndrome is characterized by recurrent episodes of wheezing, mucus production, pulmonary infiltrates, and elevated levels of serum IgE. Many patients develop central bronchiectasis, and a subset will go on to end-stage fibrotic lung disease. It is thought that treatment will prevent this progression. The mainstay of therapy remains oral corticosteroids.
MY ROLE IN THE DISCOVERY AND CLASSIFICATION OF THE ENTEROVIRUSES
Authors: Melnick Joseph L.
Published: July 2002

The enteroviruses constitute one of the genera of the picornavirus family. The genus includes the polioviruses, the coxsackieviruses, and the echoviruses of humans, plus a number of enteroviruses of lower animals (e.g. monkeys, cattle, pigs, mice). Over 100 serotypes are recognized, of which the first to be discovered were the polioviruses. It was my good fortune to have been a scientist during the golden age of virology, when new techniques were being introduced into the field. These often led to the discovery of new viruses. This article details the isolation of the enteroviruses, their recognition as a separate genus of Picornaviridae, and my role in the process. Poliovirus, the most hazardous of the group, is almost gone from the world, but the other enteroviruses will be with us for some time. Several members of the Committee dealing with these agents—Enders, Sabin, Dalldorf, Syverton—have passed on, but the work of this Committee to which I was privileged to contribute will live long.
CHARMONIUMSUPPRESSION INHEAVY-IONCOLLISIONS
Authors: Gerschel C. , Hüfner J.
Published: July 2002

▪ Abstract  Data and their interpretations are reviewed for J/ψ and ψ′ production in heavy-ion collisions with particular emphasis on the recently reported anomaly in Pb-Pb reactions. The observed suppressions in pA collisions are discussed in terms of final-state absorption of a pre-meson and the pTdistributions due to parton scattering in the initial state. The experimental setup is described and the various results for J/ψ and ψ′ suppressions, including their pT-dependence, are presented. The data, in particular the observed anomalous suppression in Pb-Pb collisions, are discussed in the light of the proposed ideas, among them quark-gluon plasma formation and suppression via co-movers.
COLLECTIVE FLOW IN HEAVY-ION COLLISIONS
Authors: Herrmann Norbert , Wessels Johannes P. , Wienold Thomas
Published: July 2002

▪ Abstract  This chapter presents an experimental overview of collective flow phenomena in heavy-ion collisions in the incident energy regime from 100 AMeV to 160 AGeV. The characteristic features of various types of flow are described. The discussion of common dependences on the collision system and bombarding energy focuses on the different time scales of the underlying physics processes. Special emphasis is placed on the presence of structures in the excitation functions. The sensitivity of the available data to changes of nuclear-matter properties, e.g. equation of state, medium effects, and phase transitions, is discussed.
High-Energy Neutrino Astrophysics
Authors: Learned John G. , Mannheim Karl
Published: July 2002

▪ Abstract  High-energy (>100 MeV) neutrino astrophysics enters an era of opportunity and discovery as the sensitivity of detectors approaches astrophysically relevant flux levels. We review the major challenges for this emerging field, among which the nature of dark matter, the origin of cosmic rays, and the physics of extreme objects such as active galactic nuclei, gamma-ray bursts, pulsars, and supernova remnants are of prime importance. Variable sources at cosmological distances allow the probing of neutrino propagation properties over baselines up to about 20 orders of magnitude larger than those probed by terrestrial long-baseline experiments. We review the possible astrophysical sources of high-energy neutrinos, which also act as an irreducible background to searches for phenomena at the electroweak and grand-unified-theory symmetry-breaking scales related to possible supersymmetric dark matter and topological defects. Neutrino astronomy also has the potential to discover previously unimagined high-energy sources invisible in other channels and provides the only means for direct observations of the early universe prior to the era of decoupling of photons and matter. We conclude with a discussion of experimental approaches and a short report on present projects and prospects. We look forward to the day when it will be possible to see the universe through a new window in the light of what may be its most numerous particle, the elusive neutrino.
PHARMACOLOGY OF NEUROTROPHIC FACTORS
Authors: Hefti Franz
Published: July 2002

▪ Abstract  The field of neurotrophic factor pharmacology emerged during the past decade with the discovery that these proteins can counteract neuronal atrophy and death in the adult nervous system. These concepts are being tested in clinical trials. Therapeutic use of neurotrophic proteins seems practical for diseases of the peripheral nervous system (PNS), where they can be given by systemic administration. For diseases of the CNS, special administration strategies will have to be developed to deliver the neurotrophic factors into the brain. The development of small molecule mimetics represents an alternative approach that is actively pursued to provide brain-penetrant neurotrophics.
A QUEST FOR ERYTHROPOIETIN OVER NINE DECADES
Authors: Fisher James W.
Published: July 2002

[Figure: see text]

▪ Abstract  The major research accomplishments of the author are described from the time of his PhD thesis work on the mechanism of cobalt polycythemia to the present day. His early work on the quest for the cell that produces erythropoietin (Epo) to his current work on oxygen sensing and signal transduction pathways involved in erythropoietin gene expression are reported. He describes his main research interest in the mechanism of cobalt polycythemia between 1954 and 1962 and his research on how hormones such as the glucocorticoids function in the regulation of erythropoiesis (1956–1962). His major findings during this period were the discovery that hydrocortisone and corticosterone stimulated erythropoiesis (1958) and that cobalt increased erythropoietin production in the isolated perfused dog kidney (1961). He describes how he was led astray in some of his early studies on the cells in the kidney that produce erythropoietin, because of the less-developed technology available to him at that time; and how in situ hybridization and other molecular biology techniques enabled him to confirm some of the earlier work in mice by other investigators that interstitial cells in the kidney were the site of production of erythropoietin in the primate. His work in the controversial area of the mechanism of the anemia of end-stage renal disease is described in detail, as it pertains to Epo deficiency and suppressed erythroid progenitor cell response to Epo. He also discusses his recent work on signal transduction pathways (hypoxia, nitric oxide, adenosine, and C kinase) in oxygen sensing and Epo gene expression.
Targets of Drug Action
Authors: Burgen A.S.V.
Published: July 2002

This article considers early work from the author’s laboratory on muscarinic receptor specificity, subtypes, and conformational variability, with the use of nuclear magnetic resonance in pharmacology and the conformational variants of dihydrofolate reductase and general questions of receptors. It also considers some current approaches to drug development and receptor function, particularly as influenced by increasing knowledge of three-dimensional structure of receptors.
Genetic Variations and Polymorphisms of G Protein-Coupled Receptors: Functional and Therapeutic Implications
Authors: Rana Brinda K , Shiina Tetsuo , Insel Paul A
Published: July 2002

G protein-coupled receptors (GPCRs) represent a major class of proteins in the genome of many species, including humans. In addition to the mapping of a number of human disorders to regions of the genome containing GPCRs, a growing body of literature has documented frequently occurring variations (i.e. polymorphisms) in GPCR loci. In this article, we use a domain-based approach to systematically examine examples of genetic variation in the coding and noncoding regions of GPCR loci. Data to date indicate that residues in GPCRs are involved in ligand binding and coupling to G proteins and that regulation can be altered by polymorphisms. Studies of GPCR polymorphisms have also uncovered the functional importance of residues not previously implicated from other approaches that are involved in the function of GPCRs. We predict that studies of GPCR polymorphisms will have a significant impact on medicine and pharmacology, in particular, by providing new means to subclassify patients in terms of both diagnosis and treatment.
FAST NATURAL AND MAGNETIC CIRCULAR DICHROISM SPECTROSCOPY
Authors: Goldbeck Robert A. , Kim-Shapiro Daniel B. , Kliger David S.
Published: July 2002

▪ Abstract  The addition of circular or, more generally, elliptical polarization state detection to fast optical absorption spectroscopy can increase the amount of electronic and nuclear conformational information obtained about transient molecular species. To accomplish this, fast circular dichroism methods have emerged over the past decade that overcome the millisecond limit on time resolution associated with conventional modulation techniques and enable structural studies of excited states and kinetic intermediates. This article reviews techniques for time-resolved natural and magnetic circular dichroism spectroscopy covering the picosecond to millisecond time regimes and their applications, with particular emphasis on quasi-null ellipsometric techniques for nanosecond multichannel measurements of circular dichroism. Closely related quasi-null polarimetric techniques for nanosecond optical rotatory dispersion and linear dichroism measurements are also discussed.
ATTACHMENT AND SEPARATION IN YOUNG CHILDREN
Authors: Field Tiffany
Published: July 2002

▪ Abstract  Attachment theory is criticized for being based on momentary stressful situations, for being limited to behaviors that occur with the primary attachment figure, for including only overt behaviors in its paradigm, and for failing to consider multiple attachments at different stages of life. A model of psychological attunement is then presented and supported by several studies documenting behavioral, physiological, and biochemical responses to separations from parents and peers.
Linkage of Essential Hypertension to Chromosome 18q
Authors: Kristjansson Kristleifur , Manolescu Andrei , Kristinsson Arni , Hardarson Thordur , Knudsen Helga , Ingason Sigurdur , Thorleifsson Gudmar , Frigge Michael L. , Kong Augustine , Gulcher Jeffrey R. , Stefansson Kari
Published: July 2002

We performed a genomewide scan with 904 microsatellite markers using 120 extended Icelandic families with 490 hypertensive patients. The families were identified by cross-matching a list of hypertensive patients from the Hypertension Clinic of the University Hospital (Landspitalinn) in Iceland with a genealogy database of the entire Icelandic nation. After adding 5 markers, we found linkage to chromosome 18q with an allele-sharing LOD score of 4.60 (
P
=2.1× 10
−6
). These results provide evidence for a novel susceptibility gene for essential hypertension on chromosome 18q and show that it is possible to study the genetics of essential hypertension without stratifying by subphenotypes.
Functional Reconstitution of Vascular Smooth Muscle Cells With cGMP-Dependent Protein Kinase I Isoforms
Authors: Feil Robert , Gappa Nicolai , Rutz Mark , Schlossmann Jens , Rose Christine R. , Konnerth Arthur , Brummer Sabine , Kühbandner Susanne , Hofmann Franz
Published: July 2002

The cGMP-dependent protein kinase type I (cGKI) is a major mediator of NO/cGMP-induced vasorelaxation. Smooth muscle expresses two isoforms of cGKI, cGKIα and cGKIβ, but the specific role of each isoform in vascular smooth muscle cells (VSMCs) is poorly understood. We have used a genetic deletion/rescue strategy to analyze the functional significance of cGKI isoforms in the regulation of the cytosolic Ca
2+
concentration by NO/cGMP in VSMCs. Cultured mouse aortic VSMCs endogenously expressed both cGKIα and cGKIβ. The NO donor diethylamine NONOate (DEA-NO) and the membrane-permeable cGMP analogue 8-bromo-cGMP inhibited noradrenaline-induced Ca
2+
transients in wild-type VSMCs but not in VSMCs genetically deficient for both cGKIα and cGKIβ. The defective Ca
2+
regulation in cGKI-knockout cells could be rescued by transfection of a fusion construct consisting of cGKIα and enhanced green fluorescent protein (EGFP) but not by a cGKIβ-EGFP construct. Fluorescence imaging indicated that the cGKIα-EGFP fusion protein was concentrated in the perinuclear/endoplasmic reticulum region of live VSMCs, whereas the cGKIβ-EGFP protein was more homogeneously distributed in the cytoplasm. These results suggest that one component of NO/cGMP-induced smooth muscle relaxation is the activation of the cGKIα isoform, which decreases the noradrenaline-stimulated cytosolic Ca
2+
level.
Delusions of Dialogue: Control and Choice in Interactive Art
Authors: Campbell Jim
Published: July 2002

The author discusses the relationship of interactive art to the structure of the computer, in particular commenting on artists' choices in using different kinds of systems, programs and interface devices. He discusses the problems inherent in the reduction of an artist's concept to a mathematical representation, a transformation that is necessary to allow a work to be implemented on a computer. Discussing the potential of the computer to allow a work to be able to change and grow over time through the extraction and storage of information, he looks for new, untouched directions for interactive art.
Was Scriabin a Synesthete?
Authors: Galeyev B. M. , Vanechkina I. L.
Published: July 2002

This survey and summary of documentary material on Scriabin's “color hearing” is being presented for consideration by researchers studying his ideas of light-music synthesis. On the basis of their analysis, the authors conclude that the nature of Scriabin's “color-tonal” analogies was associative, i.e. psychological; accordingly, the existing belief that Scriabin was a distinctive, unique “synesthete” who really saw the sounds of music—that is, literally had an ability for “co-sensations”—is placed in doubt.
The Role of Artists in Ship Camouflage During World War I
Authors: Behrens Roy R.
Published: July 2002

Experiments in ship camouflage during World War I were necessitated by the inordinate success of German submarines (called “U-boats”) in destroying Allied ships. Because it is impossible to make a ship invisible at sea, Norman Wilkinson, Everett L. Warner and other artists devised methods of course distortion in which high-contrast, unrelated shapes were painted on a ship's surface, thereby confusing the periscope view of the submarine gunner.
Control Is Not Movement
Authors: Culicover Peter W. , Jackendoff Ray
Published: July 2002

We present arguments against Hornstein's recent movement theory of control. Such a theory can be sustained only if a restricted subset of the data is considered. We review additional data that show that the position of the controller is determined at least in part by semantic constraints. A semantic account captures the generalizations in a manner impossible for a syntactic account.
Formal and Empirical Arguments concerning Phonological Acquisition
Authors: Hale Mark , Reiss Charles
Published: July 2002

Smolensky (1996a) has proposed an ingenious solution to the well-known “comprehension/production” dilemma in phonological acquisition. In this article we argue that Smolensky's model encounters serious difficulties with respect to the parsing algorithm proposed and the learnability of underlying representations. Drawing on the generative literature in phonological acquisition, as well as the work of phoneticians and psycholinguists, we offer alternative parsing algorithms and examine their implications for learnability and the initial ranking of Optimality Theory constraints. Finally, we propose that the resolution of the comprehension/production dilemma lies not in the phonological domain (linguistic competence), but in the domain of the implementation of linguistic knowledge (performance).
Meeting Report: Transcranial Magnetic Stimulation and Studies of Human Cognition
Authors: Fitzpatrick Susan M. , Rothman Douglas L.
Published: July 2002

A James S. McDonnell Foundation workshop1 examined the role of TMS in studies of human cognition. A summary of the workshop presentations, discussion, and the recommendations appear below.2 A selected reference list is provided at the end of the summary.