bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-asymmetry in business processes
Authors: Cheung Michael Tow , Liao Ziqi
Published: July 2002

A back and forth challenge for the design of a digital nervous system.
Remedies for common user-agent problems
Authors: Dubost Karl , Haas Hugo , Jacobs Ian
Published: July 2002

User agents---that is browsers and other programs that deal with the Web---can fail the user in many ways. This article, by three people deeply involved with the development of the Web, documents some typical common user agent problems, and suggests correct ways of working.The authors use several Web-specific technical terms, so let me list the important ones here:• Fragment identifier: the part of a URI Web address after a `#' character, typically identifying a sub-part of a document (e.g. http://www.example.com/index.html#contact).• HTTP: hypertext transfer protocol - the protocol used for transferring documents between a server and a client.• Media type (also known as MIME type): an identifying string like "text/html" or "image/gif" used by servers and clients for identifying the type of a document.• PNG: a bitmapped image format, like GIF and JPEG, but with better user experience properties• RFC: `Request for comments' - the name given to Internet standards published by the IETF (Internet Engineering Task Force)• SVG: structured vector graphics: a non-bitmapped image format that scales better than bitmapped formats like PNG, GIF and JPEG.• URI: (Universal resource identifier) a `Web address', such as http://www.acm.org• URI scheme: the part of a URI before the colon, such as http: and ftp:---Steven Pemberton
A photo history of SIGCHI
Authors: Shneiderman Ben , Kang Hyunmo , Kules Bill , Plaisant Catherine , Rose Anne , Rucheir Richesh
Published: July 2002

For 20 years I have been photographing personalities and events in the emerging discipline of human--computer interaction. Until now, only a few of these photos were published in newsletters or were shown to visitors who sought them out. Now this photo history is going from a personal record to a public archive. This archive should be interesting for professional members of this community who want to reminisce, as well as for historians and journalists who want to understand what happened. Students and Web surfers may also want to look at the people who created better interfaces and more satisfying user experiences.
On first-order topological queries
Authors: Grohe Martin , Segoufin Luc
Published: July 2002

One important class of spatial database queries is the class of
topological queries
, that is, queries invariant under homeomorphisms. We study topological queries expressible in the standard query language on spatial databases, first-order logic with various amounts of arithmetic. Our main technical result is a combinatorial characterization of the expressive power of topological first-order logic on
regular
spatial databases.
Permission grids
Authors: Zelinka Steve , Garland Michael
Published: July 2002

We introduce thepermission grid, a spatial occupancy grid which can be used to guide almost any standard polygonal surface simplification algorithm into generating an approximation with a guaranteed geometric error bound. In particular, all points on the approximation are guaranteed to be within some user-specified distance from the original surface. Such bounds are notably absent from many current simplification methods, and are becoming increasingly important for applications in scientific computing and adaptive level of detail control. Conceptually simple, the permission grid defines a volume in which the approximation must lie, and does not permit the underlying simplification algorithm to generate approximations outside the volume.The permission grid makes three important, practical improvements over current error-bounded simplification methods. First, it works on arbitrary triangular models, handling all manners of mesh degeneracies gracefully. Further, the error tolerance may be easily expanded as simplification proceeds, allowing the construction of an error-bounded level of detail hierarchy with vertex correspondences among all levels of detail. And finally, the permission grid has a representation complexity independent of the size of the input model, and a small running time overhead, making it more practical and efficient than current methods with similar guarantees.
Middleware for real-time and embedded systems
Authors: Schmidt Douglas C.
Published: July 2002

Off-the-shelf middleware technology is being adapted for such mission-critical dynamic domains as online financial trading, distributed process control, even submarine information systems, avionics mission computing, radar processing, and software-defined radios.
Systematic aid for developing middleware architectures
Authors: Issarny Valérie , Kloukinas Christos , Zarras Apostolos
Published: July 2002

This development environment enables the specification, automated composition, and quality analysis of flexible, configurable middleware architectures, notably in distributed systems.
Power play
Authors: Gelsinger Patrick P.
Published: July 2002

There will always be a need for power … but at what cost?
Digital rights (and wrongs)
Authors: Fowler Dennis
Published: July 2002

New legislation intended to resolve intellectual property issues only puts opposing viewpoints in stark relief
A large deviations analysis of the transient of a queue with many Markov fluid inputs
Authors: Mandjes Michel , Ridder Ad
Published: July 2002

This article analyzes the transient buffer content distribution of a queue fed by a large number of Markov fluid sources. We characterize the probability of overflow at time
t
, given the current buffer level and the number of sources in the on-state. After scaling buffer and bandwidth resources by the number of sources
n
, we can apply large deviations techniques. The transient overflow probability decays exponentially in
n
. In case of exponential on/off sources, we derive an expression for the decay rate of the rare event probability under consideration. For general, Markov fluid sources, we present a plausible conjecture. We also provide the "most likely path" from the initial state to overflow (at time
t
). Knowledge of the decay rate and the most likely path to overflow leads to (i) approximations of the transient overflow probability, and (ii) efficient simulation methods of the rare event of buffer overflow. The simulation methods, based on importance sampling, give a huge speed-up compared to straightforward simulations. The approximations are of low computational complexity, and accurate, as verified by means of simulation experiments.
Symbol manipulation in FORTRAN
Authors: Bailey M. J. , Barnett M. P. , Burleson P. B.
Published: July 2002

A set of subroutines for use in FORTRAN are described whose purpose is to synthesize output strings from (i) input strings which have been analysed by the SHADOW general syntactic analysis subroutine reported earlier, and/or (ii) packed BCD strings formed in any way. Function-type subroutines are included for intermediate manipulations, which are performed on the strings which are stored in an abbreviated internal representation. The automatic way in which an internal representation for each newly created substring is stored sequentially in a block of common storage, and the manner in which a storage block is dynamically allocated for that purpose, are discussed.
Design and implementation of a general-purpose input routine
Authors: Hassitt A.
Published: July 2002

A general-purpose input routine is discussed and advocated for FORTRAN. The philosophy of such programs is examined and exemplified.
Multiword list items
Authors: Comfort W. T.
Published: July 2002

The
list concept
as originally proposed by Newell, Simon and Shaw specified single computer words as elements of a list. This report describes the use of two or more consecutive words as one element. Such use results in a considerable saving in both the space required to hold a given amount of data, and in the execution time required to perform a given process on the data.Following a brief description of standard list structures with single-word items, the multiword items are introduced. Then variable-length items are described, along with the corresponding space-utilization problems. Finally, several examples are given to illustrate the use of multiword lists.This paper attempts to draw together various recent papers which have applied some of these concepts in different ways, and indicate how they relate to the more general problem.
Numerical solution of nonlinear two-point boundary problems by finite difference methods
Authors: Holt James F.
Published: July 2002

Solution of nonlinear two-point boundary-value problems is often an extremely difficult task. Quite apart from questions of reality and uniqueness, there is no established numerical technique for this problem. At present, shooting techniques are the easiest method of attacking these problems. When these fail, the more difficult method of finite differences can often be used to obtain a solution. This paper gives examples and discusses the finite difference method for nonlinear two-point boundary-value problems.
Approximate solution of axially symmetric problems
Authors: Greenspan Donald
Published: July 2002

A variety of physical problems in such diverse fields as electrostatic field theory, heat and ideal fluid flow, and stress concentration theory reduce, under the assumption of axial symmetry, to the study of the elliptic partial differential equation ∂
2
u/∂x
2
+ ∂
2
u/∂y
2
+ k/y(∂u/∂y) = 0. Dirichlet-type problems associated with this equation are studied on regions whose boundaries include a nondegenerate portion of the x-axis and exceedingly accurate numerical methods are given for approximating solutions.
Efficient and automatic implementation of the adjoint state method
Authors: Gockenbach Mark S. , Reynolds Daniel R. , Shen Peng , Symes William W.
Published: July 2002

Combination of object-oriented programming with automatic differentiation techniques facilitates the solution of data fitting, control, and design problems driven by explicit time stepping schemes for initial-boundary value problems. The C++ class fdtd takes a complete specification of a
single step
, along with some associated code, and assembles from it a complete simulator, along with the linearized and adjoint simulations. The result is a (nonlinear) operator in the sense of the Hilbert Class Library (HCL), a C++ software package for optimization. The HCL operator so produced links directly with any of the HCL optimization algorithms. Moreover the performance of simulators constructed in this way is equivalent to that of optimized Fortran implementations.
Beyond the handset
Authors: Palen Leysia , Salzman Marilyn
Published: July 2002

Service-based wireless devices like wireless telephones require users to interact with aspects of the technology beyond the hardware and software of the handset. By entering into contractual relationships with service-providers, and by using network-based services, users interact with a larger
system
---one that has social and technological components. The operation of the wireless telephone requires the assimilation of heterogeneous sources of information from the device manufacturer, sales people, customer service representatives, marketing people, and members of the popular media, among others, which can easily confound users' understanding of this new class of technology. Opportunities for usability problems therefore scale beyond the handset, as do opportunities for better design. We report the results of a study of 19 novice wireless phone users who were closely tracked for the first 6 weeks after service acquisition. Taking a technology-as-system analytical approach, we describe the wireless telephony system as four socio-technical components: hardware, software, "netware," and "bizware." This particular organization of the system is intended for the practical application of designing for usability.
The design collaboratorium
Authors: Bødker Susanne , Buur Jacob
Published: July 2002

The "design collaboratorium" is a new usability practice that has been developed in an action research project between three industrial usability labs and a university. The design collaboratorium has been developed as a reaction to the failing capabilities of classical usability methods to cope with ubiquitous technologies. It has borrowed elements from participatory design and developed them further to become useful in large-scale industrial development organizations. The design collaboratorium will be presented through examples from a joint project: a vision project concerning wastewater treatment technology. In light of the case, we will discuss the philosophy underlying the design collaboratorium in further detail: the collaboration between active participants, the role of design artifacts, and the room as a meeting ground. Finally we lay out the working method and propose directions for future usability competencies.
OAMulator
Authors: Menczer Filippo , Segre Alberto Maria
Published: July 2002

The OAMulator is a Web-based resource to support the teaching of instruction set architecture, assembly languages, memory, addressing, high-level programming, and compilation. The tool is based on a simple, virtual CPU architecture, called the One Address Machine. A compiler allows us to take programs written in a special programming language, called OAMPL, and transform them into OAM assembly. An OAM assembler/emulator interprets and executes OAM assembly code produced by the compiler or written directly by students. The OAMulator is targeted at non-CS students who take introductory courses in information technology or information systems. Such students are normally exposed to concepts of computer hardware and software, but it is difficult for them to make the connection between the two. The OAMulator takes the mystery out of CPU architecture by letting students gain confidence with the concepts of compilers and binary execution. The Web-based deployment allows students to work on problems in convenient locations, at their own pace, and with rewarding interaction.
The Postroom Computer
Authors: Osborne Hugh
Published: July 2002

The Postroom Computer is a computer architecture simulator based on the
Little Man Computer
developed in 1965 by Stuart Madnick and John Donovan. It provides a family of architectures suitable for use in teaching introductory computer architectures. It is designed to introduce aspects of computer architecture and low-level programming in an incremental way. The extensions are designed to provide a range of computing models within the Little Man Computer paradigm. As they are introduced they can be related both to the Little Man Computer paradigm and to "real" machines. The two major extensions are a range of instruction set architectures---0, 1, 2, and 3 address machines, and a choice of addressing architectures---immediate or register operands---with a range of memory models with or without registers and/or background memory.The extensions have a high degree of orthogonality, allowing concepts to be introduced in an incremental fashion. It would, in fact, be more correct to speak of a family of Postroom Computers, rather than one Postroom Computer.
The PIPPIN machine
Authors: Decker Rick , Hirshfield Stuart
Published: July 2002

This article describes two simulations which, together, are
intended to help students make the leap from writing programs in a
simple high-level language to understanding how such programs come
to be translated and executed on a simple computer. The first
program simulates the compilation of an assignment statement from a
typical programming language into a mock assembly language. The
second program simulates the fetch-execute cycle on a computer
built expressly to process that same assembly language. We describe
the design and use of each simulator, and conclude with anecdotes
about our experiences using these tools in class.
True blue and vigilante, too
Authors: Meeks Brock N.
Published: July 2002

Does encouraging citizens to work with law enforcement to fight crime have the potential for abuse?
Rethinking the value of IT, again
Authors: Martinsons Maris G. , Martinsons Valdis
Published: July 2002

Challenging the view that IT is responsible for widespread productivity gains.
The reality of simulated actors
Authors: Smith Alvy Ray
Published: July 2002

The acting of actors will survive the digital revolution; their on-screen appearance may not.
Mammalian ABC Transporters in Health and Disease
Authors: Borst P. , Elferink R. Oude
Published: July 2002

▪ Abstract  The ATP-binding cassette (ABC) transporters are a family of large proteins in membranes and are able to transport a variety of compounds through membranes against steep concentration gradients at the cost of ATP hydrolysis. The available outline of the human genome contains 48 ABC genes; 16 of these have a known function and 14 are associated with a defined human disease. Major physiological functions of ABC transporters include the transport of lipids, bile salts, toxic compounds, and peptides for antigen presentation or other purposes. We review the functions of mammalian ABC transporters, emphasizing biochemical mechanisms and genetic defects. Our overview illustrates the importance of ABC transporters in human physiology, toxicology, pharmacology, and disease. We focus on three topics: (a) ABC transporters transporting drugs (xenotoxins) and drug conjugates. (b) Mammalian secretory epithelia using ABC transporters to excrete a large number of substances, sometimes against a steep concentration gradient. Several inborn errors in liver metabolism are due to mutations in one of the genes for these pumps; these are discussed. (c) A rapidly increasing number of ABC transporters are found to play a role in lipid transport. Defects in each of these transporters are involved in human inborn or acquired diseases.
Catalytic Strategies of the Hepatitis Delta Virus Ribozymes
Authors: Shih I-hung , Been Michael D.
Published: July 2002

▪ Abstract  The hepatitis delta virus (HDV) ribozymes are self-cleaving RNA sequences critical to the replication of a small RNA genome. A recently determined crystal structure together with biochemical and biophysical studies provides new insight into the possible catalytic mechanism of these ribozymes. The HDV ribozymes are examples of naturally occurring small ribozymes that catalyze cleavage of the RNA backbone with a rate enhancement of 106- to 107-fold over the uncatalyzed rate. To achieve this level of rate enhancement, the HDV ribozymes have been proposed to employ several catalytic strategies that include the use of metal ions, intrinsic binding energy, and a novel example of general acid-base catalysis with a cytosine side chain acting as a proton donor or acceptor.
Structural and Thermodynamic Correlates of T Cell Signaling
Authors: Rudolph Markus G. , Luz John G. , Wilson Ian A.
Published: July 2002

▪ Abstract  The first crystal structures of intact T cell receptors (TCRs) bound to class I peptide-MHC (pMHCs) antigens were determined in 1996. Since then, further structures of class I TCR/pMHC complexes have explored the degree of structural variability in the TCR-pMHC system and the structural basis for positive and negative selection. The recent determination of class II and allogeneic class I TCR/pMHC structures, as well as those of accessory molecules (e.g., CD3), has pushed our knowledge of TCR/pMHC interactions into new realms, shedding light on clinical pathologies, such as graft rejection and graft-versus-host disease. Furthermore, the determination of coreceptor structures lays the foundation for a more comprehensive structural description of the supramolecular TCR signaling events and those assemblies that arise in the immunological synapse. While these telling photodocumentaries of the TCR/pMHC interaction are composed mainly from static crystal structures, a full description of the biological snapshots in T cell signaling requires additional analytical methods that record the dynamics of the process. To this end, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and ultracentrifugation (UC) have furnished both affinities and kinetics of the TCR/pMHC association. In the past year, structural, biochemical, and molecular biological data describing TCR/pMHC interactions have sublimely coalesced into a burgeoning well of understanding that promises to deliver further insights into T cell recognition. The coming years will, through a more intimate union of structural and kinetic data, allow many pressing questions to be addressed, such as how TCR/pMHC ligation is affected by coreceptor binding and what is the mechanism of TCR signaling in both early and late stages of T cell engagement with antigen-presenting cells.
Density Functional Methods in the Statistical Mechanics of Materials
Authors: Oxtoby David W.
Published: July 2002

▪ Abstract  Methods of density functional theory in statistical mechanics have been applied extensively over the past 15 years to problems in the equilibrium and dynamic properties of materials. They allow the incorporation of microscopic atomic and molecular forces at a much lower computational cost than direct simulation. This review discusses recent advances in the calculation of density functionals for materials, with particular emphasis on fluids at walls and in porous media, on crystal nucleation and growth from the melt, and on complex fluids and biomolecules. The extension of equilibrium density functional methods to approximate theories of phase transition dynamics is emphasized.
Free-Energy Calculations in Materials Research
Authors: Rickman J. M. , LeSar R.
Published: July 2002

▪ Abstract  Various methods for calculating the free energies of fluids, solids, and discrete spin systems are reviewed with particular emphasis on applications relevant in materials science. First, traditional methodologies based on harmonic approximations and thermodynamic integration are examined to highlight the workings of these very useful and robust techniques. Several newer and more specialized strategies are then discussed to provide a snapshot of current practices. Our aim here is to compare and contrast several related techniques and to provide an assessment of their relative strengths.
AMPA Receptor Trafficking and Synaptic Plasticity
Authors: Malinow Roberto , Malenka Robert C.
Published: July 2002

▪ Abstract  Activity-dependent changes in synaptic function are believed to underlie the formation of memories. Two prominent examples are long-term potentiation (LTP) and long-term depression (LTD), whose mechanisms have been the subject of considerable scrutiny over the past few decades. Here we review the growing literature that supports a critical role for AMPA receptor trafficking in LTP and LTD, focusing on the roles proposed for specific AMPA receptor subunits and their interacting proteins. While much work remains to understand the molecular basis for synaptic plasticity, recent results on AMPA receptor trafficking provide a clear conceptual framework for future studies.
The Human Genome Project and Its Impact on Psychiatry
Authors: Cowan W. Maxwell , Kopnisky Kathy L. , Hyman Steven E.
Published: July 2002

▪ Abstract  There has been substantial evidence for more than three decades that the major psychiatric illnesses such as schizophrenia, bipolar disorder, autism, and alcoholism have a strong genetic basis. During the past 15 years considerable effort has been expended in trying to establish the genetic loci associated with susceptibility to these and other mental disorders using principally linkage analysis. Despite this, only a handful of specific genes have been identified, and it is now generally recognized that further advances along these lines will require the analysis of literally hundreds of affected individuals and their families. Fortunately, the emergence in the past three years of a number of new approaches and more effective tools has given new hope to those engaged in the search for the underlying genetic and environmental factors involved in causing these illnesses, which collectively are among the most serious in all societies. Chief among these new tools is the availability of the entire human genome sequence and the prospect that within the next several years the entire complement of human genes will be known and the functions of most of their protein products elucidated. In the meantime the search for susceptibility loci is being facilitated by the availability of single nucleotide polymorphisms (SNPs) and by the beginning of haplotype mapping, which tracks the distribution of clusters of SNPs that segregate as a group. Together with high throughput DNA sequencing, microarrays for whole genome scanning, advances in proteomics, and the development of more sophisticated computer programs for analyzing sequence and association data, these advances hold promise of greatly accelerating the search for the genetic basis of most mental illnesses while, at the same time, providing molecular targets for the development of new and more effective therapies.
HIGHER-ORDER OPTICAL CORRELATION SPECTROSCOPY IN LIQUIDS
Authors: Fourkas John T.
Published: July 2002

▪ Abstract  Linear optical spectroscopies have long been used to study the behavior of liquids. Laser technology has progressed to the point that it has become possible to perform nonlinear optical experiments that probe higher-order correlation functions in liquids, opening a new window into our understanding of the microscopic details of solution-phase processes. Here we review advances that have been made in recent years in employing higher-order electronic and vibrational spectroscopies to study liquid-state dynamics and structure.
CHEMICALSHIFTS INAMINOACIDS, PEPTIDES,ANDPROTEINS: From Quantum Chemistry to Drug Design
Authors: Oldfield Eric
Published: July 2002

▪ Abstract  This chapter discusses recent progress in the investigation and use of13C,15N, and19F nuclear magnetic resonance (NMR) chemical shifts and chemical shift tensors in proteins and model systems primarily using quantum chemical (ab initio Hartree-Fock and density functional theory) techniques. Correlations between spectra and structure are made and the techniques applied to other spectroscopic and electrostatic properties as well, including hydrogen bonding, ligand binding to heme proteins, J-couplings, electric field gradients, and atoms-in-molecules theory, together with a brief review of the use of NMR chemical shifts in drug design.
ELECTRON TRANSFER AT MOLECULE-METAL INTERFACES: A Two-Photon Photoemission Study
Authors: Zhu X.-Y.
Published: July 2002

▪ Abstract  Electron transfer between a molecular resonance and a metal surface is a ubiquitous process in many chemical disciplines, ranging from molecular electronics to surface photochemistry. This problem has been probed recently by two-photon photoemission spectroscopy. The first photon excites an electron from an occupied metal state to an unoccupied molecular resonance. Subsequent evolution of the excited electronic wavefunction is probed in energy, momentum, and time domains by the absorption of a second photon, which ionizes the electron for detection. These experiments reveal the important roles of molecule-metal wavefunction mixing, intermolecular band formation, polarization, and localization in interfacial electron transfer.
Ethnic Boundaries and Identity in Plural Societies
Authors: Sanders Jimy M.
Published: July 2002

▪ Abstract  This paper reviews studies of ethnicity in plural societies. The literature concentrates on the social networks of ethnic groups, the use of social capital derived from these networks, and ethnic identity. I give particular attention to studies that consider how interpersonal networks within ethnic communities influence the degree of closure in social boundaries and the degree to which ethnic identity is retained. Most of the studies considered here have been published during the past two decades. However, a few earlier studies are considered so as to frame recent work in an appropriate context. Two main research foci characterize contemporary studies—forms of economic action undertaken by the immigrant generation and the socialization experiences of their offspring. Related areas of study also addressed in this review include how participation in ethnic churches, metropolitan and regional concentrations of ethnic populations, and transnationalism influence ethnic groups' experiences. I conclude by suggesting a few directions for future research.
The Study of Islamic Culture and Politics: An Overview and Assessment
Authors: Moaddel Mansoor
Published: July 2002

▪ Abstract  Among the four major world cultural traditions—Confucianism, Hinduism, Islam, and Christianity—Islam appears to have the most pervasive role in contemporary politics. The vast and varied spectrum of the scholarly works that have addressed this distinctive phenomenon started with a tradition that presumed a conflict between Islam and political modernity, while noting the centrality and universality of the faith for Muslims. This conception runs contrary to the admission of the reality of secular politics in historical Islam. If there is, on the contrary, a congruity between Islam and modernity, one still needs to provide an account of the speecificity of Muslim politics. Addressing this issue, another tradition stressed that because of its very survival into the modern era, the great Islamic tradition can play a significant role in political modernization and nation building. While this argument may be true in the cases of the historical experiences of a number of Islamic countries in the early twentieth century, it is not consistent with the overly transnational and other worldly objectives of radical Islamism of late. A third tradition opted for the analysis of the macro social processes in order to account for the rise of political Islam, while a fourth focused on the micro processes of the objectification of religion and the fragmentation of religious authority to explain Muslim politics. These explanations, however, would be incomplete without a serious assessment of the role of the rentier economy in the rise of Muslim exceptionalism. Following a critical assessment of the extant literature, this essay makes several suggestions for future research.
Barking up the Wrong Branch: Scientific Alternatives to the Current Model of Sociological Science
Authors: Lieberson Stanley , Lynn Freda B.
Published: July 2002

A fortiori it is unlikely that a mere repetition of the tricks which served us so well in physics will do for the social phenomena too. (John von Neumann and Oskar Morgenstern 1944, p. 6) I do not think the relationship between theory and measurement in the social sciences is much like what Kuhn describes for physics. Talcott Parsons was right about the lack of interaction between the two in sociology. If Kuhn is right about the preconditions for such interaction in physics, and if physics is the model for sociology, then it will be a long time before measurement makes an important contribution to sociology as a basic science …. But sociology is not like physics. Nothing but physics is like physics …. (Otis Dudley Duncan 1984, p. 169)

▪ Abstract  The standard for what passes as scientific sociology is derived from classical physics, a model of natural science that is totally inappropriate for sociology. As a consequence, we pursue goals and use criteria for success that are harmful and counterproductive. Even those dismissing such efforts use the standards of physics as grounds for their objection. Although recognizing that no natural science can serve as an automatic template for our work, we suggest that Darwin's work on evolution provides a far more applicable model for linking theory and research since he dealt with obstacles far more similar to our own. This includes drawing rigorous conclusions based on observational data rather than true experiments; an ability to absorb enormous amounts of diverse data into a relatively simple system that did not include a large number of what we think of as independent variables; the absence of prediction as a standard for evaluating the adequacy of a theory; and the ability to use a theory that is incomplete in both the evidence that supports it and in its development. Other sciences are briefly cited as well, but the main emphasis is on the lessons that Darwin provides for social sciences such as sociology that obtain their evidence primarily from non-experimental sources.
New Materials and Procedures to Protect Metallic PEM Fuel Cell Bipolar Plates
Authors: Cunningham N. , Guay D. , Dodelet J. P. , Meng Y. , Hlil A. R. , Hay A. S.
Published: July 2002

High carbon content polymers have been synthesized and pyrolyzed between 600 and 850°C in inert ambient, during various pyrolysis times, to obtain freestanding carbon films with specific resistivities that can be as low as

∼
0.01

Ω cm. One of these polymers (M2-48), with a low specific resistivity at low pyrolysis temperature and pyrolysis time, can be easily sprayed on stainless steel 316L, a possible material to be used for bipolar plates in polymer electrolyte membrane (PEM) fuel cells. The layer of M2-48 on SS316L is used as a first layer of a three-layer coating, which is able, after its pyrolysis at 750°C, to protect the stainless steel against corrosion in fuel cell tests. The second and third layers of the 70-100 μm thick protective coating are made of a commercial graphite spray and a top layer of M2-48, respectively. © 2002 The Electrochemical Society. All rights reserved.
Atherosclerosis in C3H/HeJ Mice Reconstituted With Apolipoprotein E-Null Bone Marrow
Authors: Shi Weibin , Wang Xuping , Tangchitpiyanond Khan , Wong Jack , Shi Yishou , Lusis Aldons J.
Published: July 2002

Previous studies showed that reconstitution of atherosclerosis-susceptible C57BL/6 (B6) female mice with apolipoprotein E (apoE)-deficient (apoE−/−) bone marrow resulted in markedly increased atherosclerosis, despite the fact that plasma lipid levels were unchanged. To determine whether apoE−/−bone marrow would increase atherosclerosis in an atherosclerosis-resistant strain, female C3H/HeJ (C3H) mice were lethally irradiated and reconstituted with bone marrow from either C3H.apoE−/−mice or wild-type C3H mice. Four weeks after transplantation, the mice were fed an atherogenic diet for 12 weeks. We found that reconstitution of C3H mice with apoE−/−bone marrow resulted in a slight reduction in plasma apoE levels and a dramatic reduction in apoE and apolipoprotein B (apoB) in the aortic wall. Plasma apoB and cholesterol levels were unchanged, as were atherosclerotic lesions at the aortic root. These data indicate that reconstitution of C3H mice with apoE−/−bone marrow has no effect on atherosclerosis susceptibility and that apoE promotes accumulation of apoB in the vessel wall.
Role of Nuclear Factor-κB Activation in Metalloproteinase-1, -3, and -9 Secretion by Human Macrophages In Vitro and Rabbit Foam Cells Produced In Vivo
Authors: Chase Alexander J. , Bond Mark , Crook Martin F. , Newby Andrew C.
Published: July 2002

Metalloproteinase secretion by macrophages is believed to play a key role in the matrix degradation that underlies atherosclerotic plaque instability and aneurysm formation. We studied the hypothesis that nuclear factor-κB (NF-κB), a transcription factor, is necessary for metalloproteinase secretion and, hence, is a target for pharmacological intervention. Adenovirus-mediated gene transfer of the inhibitory NF-κB subunit, I-κ Bα, was achieved into human monocyte-derived macrophages in vitro and into foam cells produced in vivo in cholesterol-fed rabbits. Human macrophages and rabbit foam cells secreted matrix-degrading metalloproteinase (MMP)-9 without further stimulation, and this was not inhibited by I-κBα (11±16% and 8±10%, respectively;P> 0.05). MMP-1 secretion from human macrophages increased in response to recombinant human CD40 ligand and was inhibited 92±5% by I-κBα (n=3,P<0.05). Rabbit foam cells secreted MMP-1 and -3 without further stimulation, and this was inhibited 83±12% and 69±11%, respectively, by I-κBα (n=6 or 7,P<0.001). I-κBα did not significantly affect the expression or activity of tissue inhibitor of metalloproteinases-1 or -2. Overexpression of I-κBα inhibited collagenolytic and β-caseinolytic activity by 42±2% and 41±7%, respectively (n=3,P<0.05). Secretion of MMP-1 and MMP-3 from macrophages stimulated in vitro or in vivo depends on the activation of NF-κB. Because the inhibition of NF-κB reduces proteolytic activity, it appears to be an attractive pharmacological target in unstable atheromas.
Plasma Thrombin-Activatable Fibrinolysis Inhibitor Antigen Concentration and Genotype in Relation to Myocardial Infarction in the North and South of Europe
Authors: Juhan-Vague I. , Morange P.E. , Aubert H. , Henry M. , Aillaud M.F. , Alessi M.C. , Samnegård A. , Hawe E. , Yudkin J. , Margaglione M. , Di Minno G. , Hamsten A. , Humphries S.E.
Published: July 2002

The thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described inhibitor of fibrinolysis that decreases plasminogen binding to the fibrin surface. The plasma TAFI concentration is almost entirely genetically determined. We investigated whether plasma TAFI levels and polymorphisms located in the TAFI gene could constitute risk markers of myocardial infarction (MI). Plasma TAFI antigen (Ag) levels were assayed by ELISA and 2 TAFI gene polymorphisms (Ala147Thr and C+1542G in the 3′ untranslated region) were determined in a large European case-control study. This study compared 598 men recruited 3 to 6 months after MI with 653 age-matched controls from North Europe (Stockholm, Sweden, and London, England) and South Europe (Marseilles, France, and San Giovanni Rotondo, Italy). A TAFI Ag value above the 90th percentile was associated with a significantly lower risk of MI (odds ratio 0.55,
P
<0.02), indicating that elevated TAFI may be protective against MI. As previously shown, the 2 TAFI gene polymorphisms were in strong linkage disequilibrium and were associated with the TAFI Ag concentration, with carriers of the Thr147 and 1542C alleles having higher levels (
P
<0.0005). These effects were similar in controls and cases and in each center. There was a difference in allele frequency between cases and controls for the Ala147Thr polymorphism, with Thr147 allele carriers being more frequent in controls than in cases in 2 centers, Stockholm (
P
=0.03) and San Giovanni Rotondo (
P
=0.03); the odds ratio for the entire cohort was 0.78 (
P
<0.05). In conclusion, patients with a recent MI presented lower values of TAFI Ag and higher frequencies of the “TAFI-decreasing” alleles. The geographical differences observed do not contribute to explaining the North-South gradient in MI risk in Europe.
Enhanced Atherogenesis Is Not an Obligatory Response to Systemic Herpesvirus Infection in the ApoE-Deficient Mouse
Authors: Alber Dagmar G. , Vallance Patrick , Powell Kenneth L.
Published: July 2002

Viral and bacterial infectious agents have been implicated in the etiology of atherosclerosis. We have previously shown that a γ-herpesvirus can accelerate atherosclerosis in the apolipoprotein E–deficient (apoE−/−) mouse. To address whether a virally induced systemic immune response is sufficient to trigger enhanced atheroma formation, we infected apoE−/− mice with murine γ-herpesvirus-68 (MHV-68) or herpes simplex virus-1 (HSV-1). In this study, we show that both viruses were able to induce a cell-mediated and humoral immune response in the apoE−/− mouse, which was sustained over a period of 24 weeks. Although intranasal or intraperitoneal infection with MHV-68 induced similar levels of virus-specific IgG1 and IgG2a antibodies in the serum of apoE−/− mice, those infected with HSV-1 showed higher anti–HSV-1 IgG2a compared with IgG1 antibody levels. In addition, viral message was not detected in the aortas of HSV-1–infected animals, whereas we have shown previously that MHV-68 mRNA can be detected in the aortas of infected mice as early as 5 days after infection. Compared with control mice, apoE−/− mice infected with MHV-68 showed accelerated atherosclerosis, whereas mice infected with HSV-1 did not. These data indicate that a systemic immune response to any particular infectious agent is insufficient to induce enhanced atherosclerosis in the apoE−/− mouse and point to specific infections or immune mechanisms that might be essential for virally enhanced atherogenesis.
Fluorescence Analysis of Biochemical Constituents Identifies Atherosclerotic Plaque With a Thin Fibrous Cap
Authors: Arakawa Koh , Isoda Kikuo , Ito Toshimitu , Nakajima Kei , Shibuya Toshio , Ohsuzu Fumitaka
Published: July 2002

Vulnerable plaque generally contains a thin fibrous cap, lipid pools, and reduced internal plaque collagen. Arterial fluorescence analysis can differentiate atherosclerotic lesions from normal arteries; however, the contribution of the lipid core to atherosclerotic arterial fluorescence remains controversial. This study aimed to identify lipid core fluorophores and to differentiate the lipid core from normal artery and atheroma. The helium-cadmium laser–induced fluorescence spectra of cadaveric arteries and known chemical constituents were recorded. Lipid core fluorescence spectra exhibited marked red shifts and broadening compared with the fluorescence spectra of normal tissue and atheroma. Similar fluorescence spectra were obtained for lipid core and oxidized low density lipoprotein, for atheroma and collagen, and for normal artery and elastin. A classification based on collagen, elastin, and oxidized low density lipoprotein spectral decomposition could discriminate the lipid core (n=29), normal artery (n=74), atheroma (n=73), and preatheroma (n=10) with 86% accuracy. Fibrous cap thickness was correlated with the spectral collagen content index (
r
=0.65,
P
<0.0001), especially at a thickness of <200 μm. We conclude that a classification algorithm based on chemical spectral decomposition can accurately classify the fluorescence spectra of normal artery, atheroma, and lipid core and may be useful in identifying vulnerable atheroma in vivo.
Propagermanium Reduces Atherosclerosis in Apolipoprotein E Knockout Mice via Inhibition of Macrophage Infiltration
Authors: Yamashita Tomoya , Kawashima Seinosuke , Ozaki Masanori , Namiki Masayuki , Inoue Nobutaka , Hirata Ken-ichi , Yokoyama Mitsuhiro
Published: July 2002

Monocyte chemoattractant protein-1 (MCP-1), which binds to C-C chemokine receptor 2, has been implicated as the primary source of monocyte chemoattractant function in the early stages of atherosclerosis. Recently, propagermanium, a drug used clinically for the treatment of chronic hepatitis in Japan, has been shown to inhibit C-C chemokine receptor 2 function and suppress monocyte/macrophage infiltration in vitro and in vivo. Given the importance of monocyte infiltration in atherogenesis, the inhibition of it by propagermanium might prevent atherosclerosis. Apolipoprotein E knockout (apoE-KO) mice were fed an atherogenic high cholesterol diet with or without 0.005% propagermanium for 8 or 12 weeks. Although the plasma lipid levels were unchanged by the drug treatment, atherosclerotic lesion area in the aortic root was reduced by 50% in the drug-treated apoE-KO mice compared with the nontreated apoE-KO mice after 8 weeks of cholesterol feeding (0.62±0.12 versus 1.27±0.07 mm
2
, respectively;
P
<0.01). Moreover, the accumulation of macrophages in the lesions was markedly reduced in the drug-treated group (macrophage positive area, 0.23±0.06 mm
2
[drug-treated group] versus 0.67±0.07 mm
2
[control group];
P
<0.01). After 12 weeks of cholesterol feeding, atherosclerotic lesion formation in the aortic root and in the descending thoracic aorta was significantly reduced in the drug-treated group. Inhibition of macrophage infiltration by propagermanium prevented the formation of atherosclerotic lesions in apoE-KO mice. This drug may serve as a therapeutic tool for the treatment of atherosclerosis.
Respiratory Uncoupling Lowers Blood Pressure Through a Leptin-Dependent Mechanism in Genetically Obese Mice
Authors: Bernal-Mizrachi Carlos , Weng Sherry , Li Bing , Nolte Lorraine A. , Feng Chu , Coleman Trey , Holloszy John O. , Semenkovich Clay F.
Published: July 2002

Insulin resistance is commonly associated with hypertension, a condition that causes vascular disease in people with obesity and type 2 diabetes. The mechanisms linking hypertension and insulin resistance are poorly understood. To determine whether respiratory uncoupling can prevent insulin resistance-related hypertension, we crossed transgenic mice expressing uncoupling protein 1 (UCP1) in skeletal muscle with lethal yellow (A
y
/a) mice, genetically obese animals known to have elevated blood pressure. Despite increased food intake, UCP-A
y
/a mice weighed less than their A
y
/a littermates. The metabolic rate was higher in UCP-A
y
/a mice than in A
y
/a mice and did not impair their ability to alter oxygen consumption in response to temperature changes, an adaptation involving sympathetic nervous system activity. Compared with their nontransgenic littermates, UCP-A
y
/a mice had lower fasting insulin, glucose, triglyceride, and cholesterol levels and were more insulin sensitive. Blood pressure, serum leptin, and urinary catecholamine levels were also lower in uncoupled mice. Independent of sympathetic nervous system activity, low-dose peripheral leptin infusion increased blood pressure in UCP-A
y
/a mice but not in their A
y
/a littermates. These data indicate that skeletal muscle respiratory uncoupling reverses insulin resistance and lowers blood pressure in genetic obesity without affecting thermoregulation. The data also suggest that uncoupling could decrease the risk of atherosclerosis in type 2 diabetes.
Role of Src Homology 2–Containing Tyrosine Phosphatase 2 on Proliferation of Rat Smooth Muscle Cells
Authors: Seki Naoto , Hashimoto Naotake , Suzuki Yoshifumi , Mori Seijiro , Amano Kimiko , Saito Yasushi
Published: July 2002

Objective

—

Src homology 2–containing phosphotyrosine phosphatase 2 (SHP2) is ubiquitously expressed and believed to function as part of a positive signaling pathway mediating growth factor–induced protein tyrosine phosphorylation. Proliferation of aortic vascular smooth muscle cells (SMCs) is an important contributor to atherosclerosis. We examined the effect of SHP2 expression on SMC proliferative activity.

Methods and Results

—

SHP2 was abundant in cultured aortic SMCs, and SHP2 staining was markedly increased in the thickened aortic intima in rats with balloon-induced injury. We obtained several SMC clones by using geneticin screening. Endogenous SHP2 expression varied among individual clones. Significant positive relationships were observed between SHP2 expression and bromodeoxyuridine uptake in SMCs stimulated by FBS, platelet-derived growth factor, or insulin-like growth factor-1. In SMCs transiently transfected with SHP2, FBS stimulation significantly increased bromodeoxyuridine uptake beyond the uptake by control SMCs.

Conclusions

—

Increased SHP2 expression in SMCs may accelerate aortic atherosclerosis by increasing cell growth.