bluuebunny/crossref_metadata_2025 huggingface dataset:
Arguments for a moratorium on the construction of a community information utility
Authors: Press Laurence I.
Published: July 2002

In this article the author urges a prudent and decentralized approach to the question of the design and desirability of computerized community information utilities. Before accepting the inevitability and desirability of this or any technology, we should: (1) be sure of the feasibility (internally and externally) of what is proposed; (2) project and perhaps wait for changes in complementary techniques; (3) evaluate current and projected supplementary techniques; (4) establish the existence of demand for what is proposed; (5) take steps to involve a representative group of ultimate users in systems design, and (6) carefully think through possible side effects on man and his world view.

Current proposals for community information utilities are examined in this framework, and the conclusion is drawn that society is not yet in a position to justify either the construction of an information utility in a prototype community or the acceptance of a policy in favor of its widespread implementation.
Subexpression ordering in the execution of arithmetic expressions
Authors: Ramamoorthy C. V. , Gonzalez M. J.
Published: July 2002

An arithmetic expression can often be broken down into its component subexpressions. Depending on the hardware environment in which the expression is to be executed, these subexpressions can be evaluated in serials, in parallel, or in a combination of these modes. This paper shows that expression execution time can be minimized only if consideration is given to the ordering of the subexpressions. In particular, subexpressions should be executed in order of decreasing memory and processor time requirements. This observation is valid for configurations ranging from a uniprocessor with an unbuffered main memory to a multiprocessor with a “cache” buffer memory. If the number of subexpressions which can be executed in parallel exceeds the number of available processors, then execution of some of these subexpressions must be postponed. A procedure is given which combines this requirement with the earlier ordering considerations to provide an optimal execution sequence.
Algorithms for finding a fundamental set of cycles for an undirected linear graph
Authors: Gotlieb C. G. , Corneil D. G.
Published: July 2002

Given the adjacency matrix of the graph, the algorithm presented in this paper finds a spanning tree and then constructs the set of fundamental cycles. Our algorithm is slower than an algorithm presented by Welch by a ratio of
N
/3 (
N
is the number of nodes) but requires less storage. For graphs with a large number of nodes and edges, when storage is limited our algorithm is superior to Welch's; however, when the graphs are small, or machine storage is very large, Welch's algorithm is superior. Timing estimates and storage requirements for both methods are presented.
SIMULA: an ALGOL-based simulation language
Authors: Dahl Ole-Johan , Nygaard Kristen
Published: July 2002

This paper is an introduction to SIMULA, a programming language designed to provide a systems analyst with unified concepts which facilitate the concise description of discrete event systems. A system description also serves as a source language simulation program. SIMULA is an extension of ALGOL 60 in which the most important new concept is that of quasi-parallel processing.
A description of the APT language
Authors: Brown S. A. , Drayton C. E. , Mittman B.
Published: July 2002

The APT (Automatically Programmed Tools) language for numerical control programming is described using the metalinguistic notation introduced in the ALGOL 60 report. Examples of APT usage are included. Presented also are an historical summary of the development of APT and a statement concerning its present status.
Approximation algorithms for metric facility location and
k
-Median problems using the primal-dual schema and Lagrangian relaxation
Authors: Jain Kamal , Vazirani Vijay V.
Published: July 2002

We present approximation algorithms for the metric uncapacitated facility location problem and the metric
k
-median problem achieving guarantees of 3 and 6 respectively. The distinguishing feature of our algorithms is their low running time:
O(m
log
m
) and
O(m
log
m(L
+ log (
n
))) respectively, where
n
and
m
are the total number of vertices and edges in the underlying complete bipartite graph on cities and facilities. The main algorithmic ideas are a new extension of the primal-dual schema and the use of Lagrangian relaxation to derive approximation algorithms.
On matrix program schemes
Authors: Ianov Iu I.
Published: July 2002

Considered are finite sets of objects A
1
, …, A
n
which we will call operations and two-place (logical) variables p
1
, …, p
k
taking the values 0 and 1.
A lower bound on the time needed in the worst case to resolve conflicts deterministically in multiple access channels
Authors: Greenberg Albert G. , Winograd Schmuel
Published: July 2002

A problem related to the decentralized control of a multiple access channel is considered: Suppose
k
stations from an ensemble of
n
simultaneously transmit to a multiple access channel that provides the feedback 0, 1, or 2+, denoting
k
= 0,
k
= 1, or
k
≥ 2, respectively. If
k
= 1, then the transmission succeeds. But if
k
≥ 2, as a result of the conflict, none of the transmissions succeed. An algorithm to
resolve
a conflict determines how to schedule retransmissions so that each of the conflicting stations eventually transmits singly to the channel. In this paper, a general model of deterministic algorithms to resolve conflicts is introduced, and it is established that, for all
k
and
n
(2 ≤
k
≤
n
), Ω(
k
(log
n
)/(log
k
)) time must elapse in the worst case before all
k
transmissions succeed.
On the power of the frame buffer
Authors: Fournier Alain , Fussell Donald
Published: July 2002

Raster graphics displays are almost always refreshed out of a frame buffer in which a digital representation of the currently visible image is kept. The availability of the frame buffer as a two-dimensional memory array representing the displayable area in a screen coordinate system has motivated the development of algorithms that take advantage of this memory for more than just picture storage. The classic example of such an algorithm is the depth buffer algorithm for determining visible surfaces of a three-dimensional scene. This paper constitutes a first attempt at a disciplined analysis of the power of a frame buffer seen as a computational engine for use in graphics algorithms. We show the inherent power of frame buffers to perform a number of graphics algorithms in terms of the number of data fields (registers) required per pixel, the types of operations allowed on these registers, and the input data. In addition to upper bounds given by these algorithms, we prove lower bounds for most of them and show most of these algorithms to be optimal.

One result of this study is the introduction of new frame buffer algorithms for computing realistic shadows and for determining the convex intersection of half spaces, an operation important in computational geometry and in rendering objects defined using planes rather than polygons. Another result is that it shows clearly the relationships between different and important areas of research in computer graphics, such as visible surface determination, compositing, and hardware for smart frame buffers.
Exception handling in scientific computing
Authors: Hull T. E. , Cohen M. S. , Sawshuk J. T. M. , Wortman D. B.
Published: July 2002

This paper describes some simple programming language facilities for raising and handling exceptions, and demonstrates, with a number of examples, their effectiveness in a scientific computing environment.

Only a small number of
predefined
exceptions need to be introduced into the language, but any number of
user-defined
exceptions can he introduced by the programmer. A key feature is that handlers are attached to operators that can raise exceptions (including user-defined functions and procedures, as well as built-in operators), rather than to expressions or statements. The programmer has a great deal of freedom in specifying what action is to be taken in case an exception arises.

The implementation and the applications are mainly concerned with scientific computing, but we believe the facilities are applicable in other areas as well.
Multiprocessor experiments for high-speed ray tracing
Authors: Gaudet Severin , Hobson Richard , Chilka Pradeep , Calvert Thomas
Published: July 2002

New single- and multiprocessor models for ray tracing are presented. Important features are (1) the use of custom VLSI building blocks, (2) the use of a modified hierarchical data-structure-based ray tracing algorithm with three disjoint data sets, and (3) scene access through adaptive information broadcasting. A modular design is presented that permits incremental performance enhancement up to two orders of magnitude over conventional minicomputers or workstations. Ray tracing is a surprisingly good application for a shared bus architecture because of the computational complexity of intersecting light rays with graphics objects.
The designer as user: building requirements for design tools from design practice
Authors: Rosson Mary Beth , Kellogg Wendy , Maass Susanne
Published: July 2002

Software tools that support the design and development of interactive computing systems are an exciting possibility. The potential pay-off is great: user interface management systems, for example, promise not only to speed the process of specifying, implementing and maintaining user interface code, but also to guide the content of the user interfaces they support. As for any tool intended for human use, however, the success of software design tools will hinge on a thorough understanding of the problems they seek to address—design as it is practiced in the real world.
Work group structures and computer support: a field experiment
Authors: Eveland J. D. , Bikson T. K.
Published: July 2002

It is frequently suggested that work groups that have computer technology to support activities such as text editing, data manipulation, and communication develop systematically different structures and working processes from groups that rely on more conventional technologies such as memos, phone calls, and meetings. However, cross-sectional or retrospective research designs do not allow this hypothesis to be tested with much power. This field experiment created two task forces, each composed equally of recently retired employees and employees still at work but eligible to retire. They were given the identical tasks of preparing reports for their company on retirement planning issues, but they were randomly assigned to different technology conditions. One group had full conventional office support; the other had, in addition, networked microcomputers with electronic mail and routine office software. Structured interviews were conducted four times during the year-long project; in addition, electronic mail activity was logged in the on-line group. Although both groups produced effective reports, the two differed significantly in the kind of work they produced, the group structures that emerged, and evaluations of their own performance. Although the standard group was largely dominated by the employees through the extensive reliance on informal meetings, the electronic technology used by the other task force allowed the retirees to exercise primary leverage. We conclude that use of computer support for cooperative work results in both quantitative and qualitative changes but that effective participation in such electronically supported groups requires significant investments of time and energy on the part of its members to master the technology and a relatively high level of assistance during the learning process.
Pygmalion at the interface
Authors: Slator Brian M. , Anderson Matthew P. , Conley Walt
Published: July 2002

Appropriate mnemonic feedback built into a natural-language interface can act as a teacher to help users acquire formal-language skills as they work, without a large initial investment of effort in a learning period.
Evaluating two massively parallel machines
Authors: Frenkel Karen A.
Published: July 2002

Two radically different parallel computers prompt a debate about the best parallel architectures and may mark the commercial viability of parallelism on the supercomputer scale.
DVI parallel image compression
Authors: Tinker Michael
Published: July 2002

At the heart of DVI is an image compression and expansion technology that uses proprietary chips to expand an image in real time from a bit stream that has been compressed on a large computer at non-real time rates. This article describes how the compression algorithm is used and how it was ported.
DEBL: a knowledge-based language for specifying and debugging distributed programs
Authors: Cheng Wan-Hong S. , Wallentine Virgil E.
Published: July 2002

DEBL provides a uniform, rigorous, and programming-language-independent environment for distributed program specification and debugging.
HDTV and the computer industry
Authors: Frenkel Karen A.
Published: July 2002

In the 1940s, television and radio combinations like the one on the left were the precursors of today's "entertainment centers ." About 25 years later, black and white television gave way to color. The next leap, high resolution television coupled with CD quality stereo may be coming soon. Last April, in the deep hours of the night, NBC, Channel 4 in New York City, announced a test: viewers would witness the first broadcast of the Sarnoff Research Center's Advanced Compatible Television system. The program of choice: the Saint Patrick's Day Parade. Researchers at the Sarnoff Center in Princeton, NJ, watched the signal, which emanated from WNBC at the World Trade Center in New York, on experimental high-definition monitors. The Sarnoff group, along with ABC and General Electric's consumer electronics division, has invested $60 million to develop a system that has twice the lines of regular TV screens (1050), scans at the same rate (29.97 frames per second), and enhances the current standard signal. A planned two-step approach to advanced television, the second phase would provide greater detail to those who bought wide-screen monitors, but it still would be compatible with today's TVs.

The Sarnoff system is one of 20 advanced television research projects under way in this country, including those of the Zenith Electronics Group in cooperation with AT&T Microelectronics, Massachusetts Institute of Technology's Advanced Television Research Program, the New York Institute of Technology, the Del-Ray Group, and North American Philips. Many have applied for matching funds from DARPA, which has earmarked $30 million for the next three years—half slated for transmission research and half for display technology. As of August 1989, five companies had been granted money for display technology. Newco Inc. of San Jose, CA, Raychem Corporation of Menlo Park, CA, Texas Instruments Inc. of Dallas, TX, and Projectavision Inc. of New York will receive money for projection display systems. Photonics Technology Inc. of Northwood, OH, was selected for flat panel display technology. More money may be forthcoming, as pressure is exerted to create systems to compete with or to supplant high-definition television (HDTV) as offered by Japan's national broadcasting organization Nippon Hoso Kyokai (NHK) and Europe's Eureka systems.
DOCUMENTS
Authors: Girill T. R. , Lulc Clement H.
Published: July 2002

An adequate delivery system for user documentation addresses the problems of easy access, versatile publication, convenient administration, and good document quality. At the National Magnetic Fusion Energy Computer Center the
DOCUMENT
program helps solve these problems by providing a high level of service through strategies that can readily be exported to other contexts. Dividing machine-readable documents into keyword windows permits fully online, subject-oriented access to all passages. An adaptive, three-tier user interface extends flexible viewing control to novices and experts alike.
DOCUMENT
also supports online subject, title, and date catalogs, and provides on-demand output of hardcopy and microfiche. Several other document delivery systems are compared with
DOCUMENT,
and all have more rigid human interfaces, more structural display units for text, or more cumbersome output options.
Lower bounds for orthogonal range searching: part II. The arithmetic model
Authors: Chazelle Bernard
Published: July 2002

Lower bounds on the complexity of orthogonal range searching in the static case are established. Specifically, we consider the following dominance search problem: Given a collection of
n
weighted points in
d
-space and a query point
q
, compute the cumulative weight of the points dominated (in all coordinates) by
q
. It is assumed that the weights are chosen in a commutative semigroup and that the query time measures only the number of arithmetic operations needed to compute the answer. It is proved that if
m
units of storage are available, then the query time is at least proportional to (log
n
/log(2
m
/
n
))

d
–*1

in both the worst and average cases. This lower bound is provably tight for
m
= Ω(
n
(log
n
)

d
–1+ϵ)

and any fixed ϵ > 0. A lower bound of Ω(
n
/log log
n
)

d

) on the time required for executing
n
inserts and queries is also established.
—Author's Abstract
Plane curves of minimal energy
Authors: Kallay Michael
Published: July 2002

The problem of finding the plane curve of minimal elastic energy with prescribed endpoints and end-directions was solved in 1983 by B. K. P. Horn. Here the solution is discussed, given a very short proof, and extended to include a constant on length.
Cultures and Communities in the Anthropology of Eastern Europe and the Former Soviet Union
Authors: Wolfe Thomas C.
Published: July 2002

▪ Abstract  Ethnographies and anthropological analyses of Eastern Europe and the former Soviet Union published in the last decade have been shaped by two major circumstances. First, they reflect the discursive possibilities opened up by the political upheavals of November 1989 in Eastern Europe and of August 1991 in the Soviet Union; second, they express and represent the theoretical heterogeneity of contemporary American anthropology. We can characterize anthropological work in the former Soviet Union as attempts to use and explore the concept of culture in various sites of social, economic, and political transformation. By contrast, anthropologists studying postsocialist societies in Eastern Europe have turned from analyses of the cultural practices of groups on the margins of modernizing state projects to accounts of how communities are shaped by systemic changes in the political economy of states.
DESATURATION AND RELATED MODIFICATIONS OF FATTY ACIDS
Authors: Shanklin John , Cahoon Edgar B.
Published: July 2002

▪ Abstract  Desaturation of a fatty acid first involves the enzymatic removal of a hydrogen from a methylene group in an acyl chain, a highly energy-demanding step that requires an activated oxygen intermediate. Two types of desaturases have been identified, one soluble and the other membrane-bound, that have different consensus motifs. Database searching for these motifs reveals that these enzymes belong to two distinct multifunctional classes, each of which includes desaturases, hydroxylases, and epoxidases that act on fatty acids or other substrates. The soluble class has a consensus motif consisting of carboxylates and histidines that coordinate an active site diiron cluster. The integral membrane class contains a different consensus motif composed of histidines. Biochemical and structural similarities between the integral membrane enzymes suggest that this class also uses a diiron cluster for catalysis. Soluble and membrane enzymes have been successfully re-engineered for substrate specificity and reaction outcome. It is anticipated that rational design of these enzymes will result in new and desired activities that may form the basis for improved oil crops.
Swinging Arms and Swinging Domains in Multifunctional Enzymes: Catalytic Machines for Multistep Reactions
Authors: Perham Richard N.
Published: July 2002

▪ Abstract  Multistep chemical reactions are increasingly seen as important in a growing number of complex biotransformations. Covalently attached prosthetic groups or swinging arms, and their associated protein domains, are essential to the mechanisms of active-site coupling and substrate channeling in a number of the multifunctional enzyme systems responsible. The protein domains, for which the posttranslational machinery in the cell is highly specific, are crucially important, contributing to the processes of molecular recognition that define and protect the substrates and the catalytic intermediates. The domains have novel folds and move by virtue of conformationally flexible linker regions that tether them to other components of their respective multienzyme complexes. Structural and mechanistic imperatives are becoming apparent as the assembly pathways and the coupling of multistep reactions catalyzed by these dauntingly complex molecular machines are unraveled.
Engineering Aspects of Hyperthermia Therapy
Authors: Roemer Robert B.
Published: July 2002

▪ Abstract  The continuing accrual of positive results in clinical cancer trials of adjunctive, synergistic hyperthermia therapy remains a strong motivation for the development of improved hyperthermia equipment and software. Indeed, the lack of needed engineering tools can be viewed as the major stumbling block to hyperthermia’s effective clinical implementation. Developing clinically effective systems will be difficult, however, because (a) it requires solving several complex engineering problems, for which (b) setting appropriate design and evaluation goals is currently difficult owing to a lack of critical biological, physiological, and clinical knowledge, two tasks which must (c) be accomplished within a complicated social/political structure.
THE SPECIFICATION OF LEAF IDENTITY DURING SHOOT DEVELOPMENT
Authors: Kerstetter R. A. , Poethig R. S.
Published: July 2002

▪ Abstract  A single plant produces several different types of leaves or leaf-like organs during its life span. This phenomenon, which is termed heteroblasty, is an invariant feature of shoot development but is also regulated by environmental factors that affect the physiology of the plant. Invariant patterns of heteroblastic development reflect global changes in the developmental status of the shoot, such as the progression from embryogenesis through juvenile and adult phases of vegetative development, culminating in the production of reproductive structures. Genes that regulate these phase-specific aspects of leaf identity have been identified by mutational analysis in both maize and Arabidopsis. These mutations have revealed that leaf production is regulated independently of leaf identity, implying that the identity of a leaf at a particular position on the shoot may depend on when the leaf was initiated in relation to a temporal program of shoot development.
MACROSCOPIC MANIFESTATIONS OF MICROSCOPIC FLOWS THROUGH POROUS MEDIA: Phenomenology from Simulation
Authors: Genabeek Olav van , Rothman Daniel H.
Published: July 2002

▪ Abstract  Recent advances in computational physics allow numerical simulation of three-dimensional complex flows through arbitrarily complex geometries. Moreover, new technology for noninvasive imaging provides detailed three-dimensional tomographic reconstructions of porous rocks with a resolution approaching one micron. These two innovations are leading to new understanding of how the microscopic complexity of natural porous media influences fluid transport at a larger, macroscopic scale. This review describes new insights concerning single-phase and multiphase porous flow derived from numerical simulation. In particular, results concerning scaling relations between macroscopic parameters, the scale dependence of transport properties, and viscous coupling in multicomponent flow are emphasized.
ON THE CONCEPT OF INDUSTRIAL ECOLOGY
Authors: Graedel T. E.
Published: July 2002

▪ Abstract  The term industrial ecology was conceived to suggest that industrial activity can be thought of and approached in much the same way as a biological ecosystem and that in its ideal form it would strive toward integration of activities and cyclization of resources, as do natural ecosystems. Beyond this attractive but fuzzy notion, little has been done to explore the usefulness of the analogy. This paper examines the structural framework of biological ecology and the tools used for its study, and it demonstrates that many aspects of biological organisms and ecosystems (for example, food webs, engineering activities, community development) do have parallels in industrial organisms and ecosystems. Some of the tools of biological ecology appear to be applicable to industrial ecology, and vice versa. In a world in which no biological ecosystem is free of human influence and no industrial ecosystem is free of biological influence, it is appropriate to abandon the artificial division between the two frameworks and develop a new synthesis—Earth system ecology—as the logical construct for all of Earth's ecosystems.
BIOGEOGRAPHY ANDCOMMUNITYSTRUCTURE OFNORTHAMERICANSEED-HARVESTERANTS
Authors: Johnson Robert A.
Published: July 2002

▪ Abstract  Seed-harvester ants are a dominant and conspicuous insect group throughout arid portions of the southwestern United States and northern Mexico, and they include ∼75 species. Intense study in the late 1970s and early 1980s led to the paradigm that interspecific competition for limited seed resources is the primary factor that structures seed-harvester ant communities. This review attempts to adjust this paradigm, suggesting that interspecific competition for food is probably less important than previously thought, whereas intraspecific competition is common and strong. Abiotic-habitat factors also have important effects on local species composition and attributes. This review also emphasizes several aspects of seed-harvester ants that have been poorly studied, including historical factors, adaptive radiation, and biogeography, to provide a more detailed evolutionary background for understanding existing species assemblages.
EVOLUTION AND MECHANISM OF TRANSLATION IN CHLOROPLASTS
Authors: Sugiura Masahiro , Hirose Tetsuro , Sugita Mamoru
Published: July 2002

▪ Abstract  The entire sequence (120 ∼ 190 kb) of chloroplast genomes has been determined from a dozen plant species. The genome contains from 87 to 183 known genes, of which half encode components involved in translation. These include a complete set of rRNAs and about 30 tRNAs, which are likely to be sufficient to support translation in chloroplasts. RNA editing (mostly C to U base changes) occurs in some chloroplast transcripts, creating start and stop codons and changing codons to retain conserved amino acids. Many components that constitute the chloroplast translational machinery are similar to those of Escherichia coli, whereas only one third of the chloroplast mRNAs contain Shine-Dalgarno–like sequences at the correct positions. Analyses conducted in vivo and in vitro have revealed the existence of multiple mechanisms for translational initiation in chloroplasts.
From the Sarcomere to the Nucleus: Role of Genetics and Signaling in Structural Heart Disease
Authors: Nicol R. L. , Frey N. , Olson E. N.
Published: July 2002

The identification of genetic mutations underlying familial structural heart disease has provided exciting new insights into how alterations in structural components of the cardiomyocyte lead to different forms of cardiomyopathy. Specifically, mutations in components of the sarcomere are frequently associated with hypertrophic cardiomyopathy, whereas mutations in cytoskeletal proteins lead to dilated cardiomyopathy. In addition, extrinsic stresses such as hypertension and valvular disease can produce myocardial remodeling that is very similar to that observed in genetic cardiomyopathy. For myocardial remodeling to occur, changes in gene expression must occur; therefore, changes in contractile function or wall stress must be communicated to the nucleus via signal transduction pathways. The identity of these signaling pathways has become a key question in molecular biology. Numerous signaling molecules have been implicated in the development of hypertrophy and failure, including the β-adrenergic receptor, Gαqand downstream effectors, mitogen-activated protein kinase pathways, and the Ca2+-regulated phosphatase, calcineurin. In the past it has been difficult to discern which signaling molecules actually contributed to disease progression in vivo; however, the development of numerous transgenic and knockout mouse models of cardiomyopathy is now allowing the direct testing of stimulatory and inhibitory molecules in the mouse heart. From this work it has been possible to identify signaling molecules and pathways that are required for different aspects of disease progression in vivo. In particular, a number of signaling pathways have now been identified that may be key regulators of changes in myocardial structure and function in response to mutations in structural components of the cardiomyocyte. Myocardial structure and signal transduction are now merging into a common field of research that will lead to a more complete understanding of the molecular mechanisms that underly heart disease.
THE WISKOTT-ALDRICH SYNDROME PROTEIN (WASP): Roles in Signaling and Cytoskeletal Organization
Authors: Snapper Scott B. , Rosen Fred S.
Published: July 2002

▪ Abstract  The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficiency that is characterized by recurrent infections, hematopoietic malignancies, eczema, and thrombocytopenia. A variety of hematopoietic cells are affected by the genetic defect, including lymphocytes, neutrophils, monocytes, and platelets. Early studies noted both signaling and cytoskeletal abnormalities in lymphocytes from WAS patients. Following the identification of WASP, the gene mutated in patients with this syndrome, and the more generally expressed WASP homologue N-WASP, studies have demonstrated that WASP-family molecules associate with numerous signaling molecules known to alter the actin cytoskeleton. WASP/N-WASP may depolymerize actin directly and/or serve as an adaptor or scaffold for these signaling molecules in a complex cascade that regulates the cytoskeleton.
Nonclassical MHC Class II Molecules
Authors: Alfonso Christopher , Karlsson Lars
Published: July 2002

Major histocompatibility complex (MHC) class II molecules are cell surface proteins that present peptides to CD4+T cells. In addition to these wellcharacterized molecules, two other class II–like proteins are produced from the class II region of the MHC, HLA-DM (DM) and HLA-DO (DO) (called H2-M, or H2-DM and H2-O in the mouse). The function of DM is well established; it promotes peptide loading of class II molecules in the endosomal/lysosomal system by catalyzing the release of CLIP peptides (derived from the class II–associated invariant chain) in exchange for more stably binding peptides. While DM is present in all class II– expressing antigen presenting cells, DO is expressed mainly in B cells. In this cell type the majority of DM molecules are not present as free heterodimers but are instead associated with DO in tight heterotetrameric complexes. The association with DM is essential for the intracellular transport of DO, and the two molecules remain associated in the endosomal system. DO can clearly modify the peptide exchange activity of DM both in vitro and in vivo, but the physiological relevance of this interaction is still only partly understood.
Complexities of CD28/B7: CTLA-4 Costimulatory Pathways in Autoimmunity and Transplantation
Authors: Salomon Benoît , Bluestone Jeffrey A.
Published: July 2002

Recent advances in the understanding of T cell activation have led to new therapeutic approaches in the treatment of immunological disorders. One attractive target of intervention has been the blockade of T cell costimulatory pathways, which result in more selective effects on only those T cells that have encountered specific antigen. In fact, in some instances, costimulatory pathway antagonists can induce antigen-specific tolerance that prevents the progression of autoimmune diseases and organ graft rejection. In this review, we summarize the current understanding of these complex costimulatory pathways including the individual roles of the CD28, CTLA-4, B7-1 (CD80), and B7-2 (CD86) molecules. We present evidence that suggests that multiple mechanisms contribute to CD28/B7-mediated T cell costimulation in disease settings that include expansion of activated pathogenic T cells, differentiation of Th1/Th2 cells, and the migration of T cells into target tissues. Additionally, the negative regulatory role of CTLA-4 in autoimmune diseases and graft rejection supports a dynamic but complex process of immune regulation that is prominent in the control of self-reactivity. This is most apparent in regulation of the CD4+CD25+CTLA-4+immunoregulatory T cells that control multiple autoimmune diseases. The implications of these complexities and the potential for use of these therapies in clinical immune intervention are discussed.
The Theory of Real Materials
Authors: Cohen Marvin L.
Published: July 2002

▪ Abstract  It has become possible to explain and predict properties of real materials using ab initio theory. The background, methods, and applications are described.
Copper Metallization for High Performance Silicon Technology
Authors: Rosenberg R. , Edelstein D. C. , Hu C.-K. , Rodbell K. P.
Published: July 2002

▪ Abstract  The increasingly rapid transition of the electronics industry to high-density, high-performance multifunctional microprocessor Si technology has precipitated migration to new materials alternatives that can satisfy stringent requirements. One of the recent innovations has been the substitution of copper for the standard aluminum-copper metal wiring in order to decrease resistance and tailor RC delay losses in the various hierarchies of the wiring network. This has been accomplished and the product shipped only since the fall of 1998, after more than a decade of intensive development. Critical fabrication innovations include the development of an electroplating process for the copper network, dual-damascence chem-mech polishing (CMP), and effective liner material for copper diffusion barrier and adhesion promotion. The present copper technology provides improved current-carrying capability by higher resistance to electromigration, no device contamination by copper migration, and the performance enhancement analytically predicted. This success of the shift to copper will accelerate the industry movement to finer features and more complex interconnect structures with sufficient device density and connectivity to integrate full systems on chips. The next innovation will be the introduction of low-dielectric constant material that, in combination with copper, will create added excitement as the industry learns how to utilize this new capability.
Arrhythmogenic Right Ventricular Dysplasia
Authors: Fontaine G. , Fontaliran F. , Hébert J.L. , Chemla D. , Zenati O. , Lecarpentier Y. , Frank R.
Published: July 2002

Arrhythmogenic right ventricular dysplasia (ARVD) is a new form of cardiomyopathy probably more frequent than commonly reported. It is a rare but important cause of sudden arrhythmic death in young, otherwise healthy persons, as well as a subtle cause of congestive heart failure. It may lead to temporary incapacitation with catastrophic consequences. Proper electrocardiographic criteria, echocardiography, nuclear medicine, or magnetic resonance imaging could identify most of these individuals. With the exception of full-thickness histological examination of the right ventricular free wall, contrast ventriculography remains the most definitive standard for a positive diagnosis. The wide clinical spectrum of arrhythmogenic right ventricular cardiomyopathies/dysplasia appears to be the result of one or possibly two factors: (a) replacement of most of the right ventricular myocardium by fat and (b) genetic susceptibility to environmental agents (myocarditis). Current treatment modalities include drug therapy, catheter or surgical ablative techniques, and modern treatments of congestive heart failure. Heart transplant is exceptional. Implantable defibrillators, used alone or in combination with drug therapy, will probably play an increasing role in ARVD and related cardiomyopathies.
Lung Transplantation at the Turn of the Century
Authors: DeMeo Dawn L. , Ginns Leo C.
Published: July 2002

▪ Abstract  Lung transplantation has become a viable treatment option for patients with end-stage lung disease. Donor selection and organ allocation must follow specific guidelines. Single, bilateral, and living-donor lobar transplantation have all been performed successfully for a variety of diseases. Complications include reimplantation response and airway complications. Rejection may occur in the hyperacute, acute, or chronic settings and requires judicious management with immunosuppression. Infection and malignancy remain potential complications of the commitment to lifelong systemic immunosuppression. Survival statistics have remained encouraging and continue to improve with experience. Improved exercise tolerance and quality of life have been demonstrated in the years following transplantation. Remaining obstacles include limited donor organ availability, long-term graft function, and patient survival. However, ongoing advances in immune tolerance and standardized training of physicians in the care of transplant patients should carry lung transplant forward in the twenty-first century.
Health Care Workforce for the Twenty-First Century: The Impact of Nonphysician Clinicians
Authors: Cooper Richard A.
Published: July 2002

▪ Abstract  For many years, nonphysician clinicians (NPCs) have participated in the care of patients. However, their numbers were small and their licensed prerogatives were narrow. Over the past decade, these characteristics have changed in three important ways. First, training in many of the NPC disciplines has increased substantially, and the growth of these disciplines is accelerating. Second, state laws and regulations have expanded both the practice prerogatives of NPCs and their autonomy from physician supervision. Third, payers have increased their access to reimbursement. As a consequence, NPCs are undertaking many elements of care that previously were provided by physicians. Their participation is generally cost-effective and is met with a high degree of patient satisfaction. This presents both opportunities and challenges to physicians as they forge new relationships with NPCs and as their own spectrum of responsibilities evolves.
Viruses and Apoptosis
Authors: Roulston Anne , Marcellus Richard C. , Branton Philip E.
Published: July 2002

▪ Abstract  Successful viral replication requires not only the efficient production and spread of progeny, but also evasion of host defense mechanisms that limit replication by killing infected cells. In addition to inducing immune and inflammatory responses, infection by most viruses triggers apoptosis or programmed cell death of the infected cell. This cell response often results as a compulsory or unavoidable by-product of the action of critical viral replicative functions. In addition, some viruses seem to use apoptosis as a mechanism of cell killing and virus spread. In both cases, successful replication relies on the ability of certain viral products to block or delay apoptosis until sufficient progeny have been produced. Such proteins target a variety of strategic points in the apoptotic pathway. In this review we summarize the great amount of recent information on viruses and apoptosis and offer insights into how this knowledge may be used for future research and novel therapies.
PATTERNING AND SPECIFICATION OF THE CEREBRAL CORTEX
Authors: Levitt Pat , Barbe Mary F. , Eagleson Kathie L.
Published: July 2002

▪ Abstract  Regionalization of the cerebral cortex occurs during development by the formation of anatomically and functionally discrete areas of the brain. Descriptive evidence based on expression of molecules and structural features suggests that an early parcelation of the cerebral wall may occur during fetal development. Experimental strategies using tissue transplants and cell culture models have explored the nature of the timing of areal specification. New signaling systems displaying the sensitivity of precursor cells to environmental cues that define the fate of neurons destined for specific areas of the cortex have been discovered. Studies in the field now suggest mechanisms of regulating cell phenotype in the cortex that are common to all parts of the neuraxis.
REGIONALIZATION OF THE PROSENCEPHALIC NEURAL PLATE
Authors: Rubenstein John L. R. , Shimamura Kenji , Martinez Salvador , Puelles Luis
Published: July 2002

▪ Abstract  Recent embryological studies are beginning to establish that the underlying organization of the forebrain may be reduced to relatively simple elements that are common to all vertebrates. We begin this chapter by reviewing studies that describe the similarities in prospective fate and molecular organization of the developing neural plate in fish, frogs, chickens, and mice. The chapter next addresses mechanisms that regulate regional specification in the anterior central nervous system. There is now evidence that the axial mesendoderm anterior to the notochord (the prechordal plate) has a central role in induction of the floor and basal plate primordia (hypothalamus) of the forebrain. Patterning of the anterolateral neural plate (telencephalon) may be regulated by FGF8 produced in the anterior neural ridge. Thus, the synthesis of information from fate mapping and experimental embryological and genetic studies is illuminating the mechanisms that generate the different components of the forebrain.
Imaging and Coding in the Olfactory System
Authors: Kauer John S , White Joel
Published: July 2002

▪ Abstract  Functional imaging methods permit analysis of neuronal systems in which activity is broadly distributed in time and space. In the olfactory system the dimensions that describe odorant stimuli in “odorant space” are still poorly defined. One way of trying to characterize the attributes of this space is to examine the ways in which its dimensions are encoded by the neurons and circuits making up the system and to compare these responses with physical-chemical attributes of the stimuli and with the output behavior of the animal. For documenting distributed events as they occur, imaging methods are among the few tools available. We are still in the early stages of this analysis; however, a number of recent studies have contributed new information to our understanding of the odorant coding problem. This paper describes imaging results in the context of other data that have contributed to our understanding of how odors are encoded by the peripheral olfactory pathway.
QUANTUM CHAOS AND COMPLEXITY IN NUCLEI
Authors: Zelevinsky Vladimir
Published: July 2002

▪ Abstract  A mesoscopic system with strong interaction between constituents, the atomic nucleus is a good candidate for studying the manifestations of quantum chaos. Recent experimental and theoretical developments give clear evidence of the dominant role chaotic dynamics plays not only in local level statistics, but also in the damping of collective motion, isospin and parity nonconservation, thermalization, and decay into continuum. In this review, those and other phenomena are discussed from the general viewpoint of quantum chaos and complexity. The complexity of eigenstates measured by information entropy in the mean-field basis is more informative than the standard signatures of chaos in the level statistics. It evolves regularly as a function of excitation energy and provides an alternative temperature scale. This sheds new light on the problems of foundations of statistical mechanics and quantum decoherence.
PERSONAL REFLECTIONS ON A GALVANIZING TRAIL
Authors: O'Dell Boyd L.
Published: July 2002

[Figure: see text]

▪ Abstract  This article encompasses my perception of, and experience in, an exciting segment of the trace element era in nutrition research: the role of zinc in the nutrition of animals and humans. Zinc has been a major player on the stage of trace element research, and it has left a trail that has galvanized the attention of many researchers, including myself. It is ubiquitous in biological systems, and it plays a multitude of physiologic and biochemical functions. A brief historical overview is followed by a discussion of the contributions the work done in my laboratory has made toward understanding the physiological and biochemical functions of zinc. The effort of 40 years has led to the belief that one of zinc's major roles, and perhaps its first limiting role, is to preserve plasma-membrane function as regards ion channels and signal transduction. Although substantial knowledge has been gained relating to the importance of zinc in nutrition, much remains to be discovered.
Toxicology Comes of Age
Authors: Doull John
Published: July 2002

▪ Abstract  [Figure: see text]

This paper contains recollections of some of the people and events that influenced the development of toxicology as an academic discipline. It also describes my experiences in pharmacology at the University of Chicago and the University of Kansas Medical Center and concludes with speculation concerning the future of toxicology.

Moderation in all things/Ne quid nimis.

     —Terence in Andria
Sodium-Calcium Exchange: A Molecular Perspective
Authors: Philipson Kenneth D. , Nicoll Debora A.
Published: July 2002

▪ Abstract  Plasma membrane Na+-Ca2+ exchange is an essential component of Ca2+ signaling pathways in several tissues. Activity is especially high in the heart where the exchanger is an important regulator of contractility. An expanding exchanger superfamily includes three mammalian Na+-Ca2+ exchanger genes and a number of alternative splicing products. New information indicates that the exchanger protein has nine transmembrane segments. The exchanger, which transports Na+ and Ca2+, is also regulated by these substrates. Some molecular information is available on regulation by Na+ and Ca2+ and by PIP2 and phosphorylation. Altered expression of the exchanger in pathophysiological states may contribute to various cardiac phenotypes. Use of transgenic approaches is beginning to improve our knowledge of exchanger function.
The Na-K-Cl Cotransporter of Secretory Epithelia
Authors: Haas Mark , Forbush III Bliss
Published: July 2002

▪ Abstract  The Na-K-Cl cotransporters are a class of ion transport proteins that transport Na, K, and Cl ions into and out of cells in an electrically neutral manner, in most cases with a stoichiometry of 1Na:1K:2Cl. To date, two Na-K-Cl cotransporter isoforms have been identified: NKCC1, which is present in a wide variety of secretory epithelia and non-epithelial cells; and NKCC2, which is present exclusively in the kidney, in the epithelial cells of the thick ascending limb of Henle’s loop and of the macula densa. Both NKCC isoforms represent part of a diverse family of cationchloride cotransport proteins that share a common predicted membrane topology; this family also includes Na-Cl cotransporters and multiple K-Cl cotransporter isoforms. In secretory epithelia, the regulation of NKCC1, which is typically present on the basolateral membrane, is tightly coordinated with that of other transporters, including apical Cl channels, to maintain cell volume and integrity during active salt and fluid secretion. Changes in intracellular [Cl] ([Cl]i) appear to be involved in this regulation of NKCC1, which is directly phosphorylated by an unknown protein kinase in response to various secretagogues as well as reductions in [Cl]i and cell volume. This review focuses on structure-function relationships within NKCC1 and on recent developments pertaining to NKCC1 regulation at cellular and molecular levels.