bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal memory management for time warp parallel simulation
Authors: Lin Yi-Bing , Preiss Bruno R.
Published: July 2002

Recently there has been a great deal of interest in performance evalution of parallel simulation. Most work is devoted to the time complexity and assumes that the amount of memory available for parallel simulation is unlimited. This paper studies the space complexity of parallel simulation. Our goal is to design an efficient memory management protocol which guarantees that the memory consumption of parallel simulation is of the same order as sequential simulation. (Such an algorithm is referred to as a
optimal
.) First, we derive the relationships among the space complexities of sequential simulation, Chandy-Misra simulation [2], and Time Warp simulation [7]. We show that Chandy-Misra may consume more storage than sequential simulation, or vice versa. Then we show that Time Warp never consumes less memory than sequential simulation. Then we describe
cancelback
, an optimal Time Warp memory management protocol proposed by Jefferson. Although cancelback is considered to be complete solution for the storage management problem in Time Warp, some efficiency issues in implementing this algorithm must be considered. We propose an optimal algorithm called
artifical rollback
. We show that this algorithm is easy to implement and analyze. An implementation of artificial rollback is given, which is integrated with processor scheduling to adjust the memory consumption rate based on the amount of free storage available in the system.
A network approach to probabilistic information retrieval
Authors: Kwok K. L.
Published: July 2002

In this article we show how probabilistic information retrieval based on document components may be implemented as a feedforward (feedbackward) artificial neural network. The network supports adaptation of connection weights as well as the growing of new edges between queries and terms based on user relevance feedback data for training, and it reflects query modification and expansion in information retrieval. A learning rule is applied that can also be viewed as supporting sequential learning using a harmonic sequence learning rate. Experimental results with four standard small collections and a large
Wall Street Journal
collection (173,219 documents) show that performance of feedback improves substantially over no feedback, and further gains are obtained when queries are expanded with terms from the feedback documents. The effect is much more pronounced in small collections than in the large collection. Query expansion may be considered as a tool for both precision and recall enhancement. In particular, small query expansion levels of about 30 terms can achieve most of the gains at the low-recall high-precision region, while larger expansion levels continue to provide gains at the high-recall low-precision region of a precision recall curve.
Computing the discrepancy with applications to supersampling patterns
Authors: Dobkin David P. , Eppstein David , Mitchell Don P.
Published: July 2002

Patterns used for supersampling in graphics have been analyzed from statistical and signal-processing viewpoints. We present an analysis based on a type of isotropic discrepancy—how good patterns are at estimating the area in a region of defined type. We present algorithms for computing discrepancy relative to regions that are defined by rectangles, halfplanes, and higher-dimensional figures. Experimental evidence shows that popular supersampling patterns have discrepancies with better asymptotic behavior than random sampling, which is not inconsistent with theoretical bounds on discrepancy.
Disco
Authors: Bugnion Edouard , Devine Scott , Govil Kinshuk , Rosenblum Mendel
Published: July 2002

In this article we examine the problem of extending modern operating systems to run efficiently on large-scale shared-memory multiprocessors without a large implementation effort. Our approach brings back an idea popular in the 1970s: virtual machine monitors. We use virtual machines to run multiple commodity operating systems on a scalable multiprocessor. This solution addresses many of the challenges facing the system software for these machines. We demonstrate our approach with a prototype called Disco that runs multiple copies of Silicon Graphics' IRIX operating system on a multiprocessor. Our experience shows that the overheads of the monitor are small and that the approach provides scalability as well as the ability to deal with the nonuniform memory access time of these systems. To reduce the memory overheads associated with running multiple operating systems, virtual machines transparently share major data structures such as the program code and the file system buffer cache. We use the distributed-system support of modern operating systems to export a partial single system image to the users. The overall solution achieves most of the benefits of operating systems customized for scalable multiprocessors, yet it can be achieved with a significantly smaller implementation effort.
An ontological analysis of the relationship construct in conceptual modeling
Authors: Wand Yair , Storey Veda C. , Weber Ron
Published: July 2002

Conceptual models or semantic data models were developed to capture the meaning of an application domain as perceived by someone. Moreover, concepts employed in semantic data models have recently been adopted in object-oriented approaches to systems analysis and design. To employ conceptual modeling constructs effectively, their meanings have to be defined rigorously. Often, however, rigorous definitions of these constructs are missing. This situation occurs especially in the case of the relationship construct. Empirical evidence shows that use of relationships is often problematical as a way of communicating the meaning of an application domain. For example, users of conceptual modeling methodologies are frequently confused about whether to show an association between things via a relationship, an entity, or an attribute. Because conceptual models are intended to capture knowledge about a real-world domain, we take the view that the meaning of modeling constructs should be sought in models of reality. Accordingly, we use ontology, which is the branch of philosophy dealing with models of reality, to analyze the meaning of common conceptual modeling constructs.
Our analysis provides a precise definition of several conceptual modeling constructs. Based on our analysis, we derive rules for the use of relationships in entity-relationship conceptual modeling. Moreover, we show how the rules resolve ambiguities that exist in current practice and how they can enrich the capacity of an entity-relationship conceptual model to capture knowledge about an application domain.
Speed is as powerful as clairvoyance
Authors: Kalyanasundaram Bala , Pruhs Kirk
Published: July 2002

We introduce resource augmentation as a method for analyzing online scheduling problems. In resource augmentation analysis the on-line scheduler is given more resources, say faster processors or more processors, than the adversary. We apply this analysis to two well-known on-line scheduling problems, the classic uniprocessor CPU scheduling problem 1 |

r
i
, pmtn|Σ F
i
,

and the best-effort firm real-time scheduling problem 1|

r
i
, pmtn

| Σ

w
i

( 1-

U
i

). It is known that there are no constant competitive nonclairvoyant on-line algorithms for these problems. We show that there are simple on-line scheduling algorithms for these problems that are constant competitive if the online scheduler is equipped with a slightly faster processor than the adversary. Thus, a moderate increase in processor speed effectively gives the on-line scheduler the power of clairvoyance. Furthermore, the on-line scheduler can be constant competitive on all inputs that are not closely correlated with processor speed. We also show that the performance of an on-line scheduler is best-effort real time scheduling can be significantly improved if the system is designed in such a way that the laxity of every job is proportional to its length.
Efficient content-based indexing of large image databases
Authors: El-Kwae Essam A. , Kabuka Mansur R.
Published: July 2002

Large image databases have emerged in various applications in recent years. A prime requisite of these databases is the means by which their contents can be indexed and retrieved. A multilevel signature file called the Two Signature Multi-level Signature File (
2SMLSF
) is introduced as an efficient access structure for large image databases. The
2SMLSF
encodes image information into binary signatures and creates a tree structures can be efficiently searched to satisfy a user's query. Two types of signatures are generated. Type
I
signatures are used at all tree levels except the leaf level and are based only on the domain objects included in the image. Type
II
signatures, on the other hand, are stored at the leaf level and are based on the included domain objects and their spatial relationships. The
2SMLSF
was compared analytically to existing signature file techniques. The
2SMLSF
significantly reduces the storage requirements; the index structure can answer more queries; and the
2SMLSF
performance significantly improves over current techniques. Both storage reduction and performance improvement increase with the number of objects per image and the number of images in the database. For an example large image database, a storage reduction of 78% may be archieved while the performance improvement may reach 98%.
Protection in operating systems
Authors: Harrison Michael A. , Ruzzo Walter L. , Ullman Jeffrey D.
Published: July 2002

A model of protection mechanisms in computing systems is presented and its appropriateness is argued. The “safety” problem for protection systems under this model is to determine in a given situation whether a subject can acquire a particular right to an object. In restricted cases, it can be shown that this problem is decidable, i.e. there is an algorithm to determine whether a system in a particular configuration is safe. In general, and under surprisingly weak assumptions, it cannot be decided if a situation is safe. Various implications of this fact are discussed.
Toward automatic program synthesis
Authors: Manna Zohar , Waldinger Richard J.
Published: July 2002

An elementary outline of the theorem-proving approach to automatic program synthesis is given, without dwelling on technical details. The method is illustrated by the automatic construction of both recursive and iterative programs operating on natural numbers, lists, and trees.

In order to construct a program satisfying certain specifications, a theorem induced by those specifications is proved, and the desired program is extracted from the proof. The same technique is applied to transform recursively defined functions into iterative programs, frequently with a major gain in efficiency.

It is emphasized that in order to construct a program with loops or with recursion, the principle of mathematical induction must be applied. The relation between the version of the induction rule used and the form of the program constructed is explored in some detail.
A slicing-based approach for locating type errors
Authors: Tip F. , Dinesh T. B.
Published: July 2002

The effectiveness of a type-checking tool strongly depends on the accuracy of the positional information that is associated with type errors. We present an approach where the location associated with an error message
e
is defined as a
slice

P
e

of the program
P
being type-checked. We show that this approach yields highly accurate positional information:

P
e

is a program that contains precisely those program constructs in
P
that caused error
e
. Semantically, we have the interesting property that type-checking

P
e

is guaranteed to produce the same error
e
. Our approach is completely language-independent and has been implemented for a significant subset of Pascal. We also report on experiments with object-oriented type systems, and with a subset of ML.
Representation results for defeasible logic
Authors: Antoniou Grigoris , Billington David , Governatori Guido , Maher Michael J.
Published: July 2002

The importance of transformations and normal forms in logic programming, and generally in computer science, is well documented. This paper investigates transformations and normal forms in the context of Defeasible Logic, a simple but efficient formalism for nonmonotonic reasoning based on rules and priorities. The transformations described in this paper have two main benefits: on one hand they can be used as a theoretical tool that leads to a deeper understanding of the formalism, and on the other hand they have been used in the development of an efficient implementation of defeasible logic.
Decomposable negation normal form
Authors: Darwiche Adnan
Published: July 2002

Knowledge compilation has been emerging recently as a new direction of research for dealing with the computational intractability of general propositional reasoning. According to this approach, the reasoning process is split into two phases: an off-line compilation phase and an on-line query-answering phase. In the off-line phase, the propositional theory is compiled into some target language, which is typically a tractable one. In the on-line phase, the compiled target is used to efficiently answer a (potentially) exponential number of queries. The main motivation behind knowledge compilation is to push as much of the computational overhead as possible into the off-line phase, in order to amortize that overhead over all on-line queries. Another motivation behind compilation is to produce very simple on-line reasoning systems, which can be embedded cost-effectively into primitive computational platforms, such as those found in consumer electronics.One of the key aspects of any compilation approach is the target language into which the propositional theory is compiled. Previous target languages included Horn theories, prime implicates/implicants and ordered binary decision diagrams (OBDDs). We propose in this paper a new target compilation language, known as decomposable negation normal form (DNNF), and present a number of its properties that make it of interest to the broad community. Specifically, we show that DNNF is universal; supports a rich set of polynomial--time logical operations; is more space-efficient than OBDDs; and is very simple as far as its structure and algorithms are concerned. Moreover, we present an algorithm for converting any propositional theory in clausal form into a DNNF and show that if the clausal form has a bounded treewidth, then its DNNF compilation has a linear size and can be computed in linear time (treewidth is a graph-theoretic parameter that measures the connectivity of the clausal form). We also propose two techniques for approximating the DNNF compilation of a theory when the size of such compilation is too large to be practical. One of the techniques generates a sound but incomplete compilation, while the other generates a complete but unsound compilation. Together, these approximations bound the exact compilation from below and above in terms of their ability to answer clausal entailment queries. Finally, we show that the class of polynomial--time DNNF operations is rich enough to support relatively complex AI applications, by proposing a specific framework for compiling model-based diagnosis systems.
Tablet: personal computer of the year 2000
Authors: Mel B. W. , Omohundro S. M. , Robison A. D. , Skiena S. S. , Thearling K. H.
Published: July 2002

A design represents a compromise between conflicting goals, and the design of the personal computer of the year 2000 is no exception. We seek something that will fit comfortably into people's lives while dramatically changing them. This may appear to be a contradiction that cannot be reconciled. But if the technology does not fit easily into the habits and lifestyles of its human users, it will be discarded by those it was meant to help. And if this new tool does not change the life of its owner, it is only because we have been too shortsighted to imagine the possibilities.

Our way out of this dilemma is to base the design upon something which is already integrated into everyone's life, to take a vital tool and give it more life. We have chosen to improve something that most people use everyday, the humble paper notebook.

We have all heard the computer revolution was supposed to eliminate paper from the workplace. Instead, it has lead to desktop publishing; now we can not only write papers but typeset them ourselves. Paper notebooks have many properties that make them particularly friendly. They are light and portable. No one thinks twice about taking a pad anywhere. They are easy and natural to use, as accessible to the toddler as to the octogenarian and as relevant to the artist as the engineer. They can be used to communicate with other people. They are the ideal medium for integrating text and graphics, and perfect for creative doodling. Moreover, notebooks are forgiving of mistakes, simply peel off the page and start anew.

It is natural to revise and edit written documents. There is something satisfying about crossing out an offending sentence from a written draft, a feeling that word processors have not captured. We aim for a computer that will provide all of these benefits and more.

Thus, the personal computer of the year 2000 will be a portable machine the size of a notebook. We will write and draw with a stylus on a screen which mimics a physical writing surface. Enhancing this with the powers of computation and communication, we create a tool that will improve the way we live and work.

This report provides a more concrete depiction of the machine we have in mind, namely TABLET.
Radical Worlds: The Anthropology of Incommensurability and Inconceivability
Authors: Povinelli Elizabeth A.
Published: July 2002

▪ Abstract  This essay seeks to provide an overview of the anthropology of radical alterity and social commensuration. I begin with critical theoretical discussions of incommensurability and undecidability in the context of radical interpretation. I then resituate these theoretical debates in liberal ideologies of language-use and public reason in order to suggest the delicate and dramatic ways in which institutionalized conventions of risk and pleasure commensurate social worlds. How do incommensurate worlds emerge and how are they sustained? In other words, how is the inconceivable conceived? How are these new ethical and epistemological horizons aligned or not in the complicated space and time of global capital and liberal democratic regionalisms and nationalisms? How do publics interpret and decide between competing social visions and practices in the shadow of the seemingly incompatible frameworks of post-foundationalist and fundamentalist enlightenments?
PLANT DISEASE RESISTANCE GENES
Authors: Hammond-Kosack Kim E. , Jones Jonathan D. G.
Published: July 2002

▪ Abstract  In “gene-for-gene” interactions between plants and their pathogens, incompatibility (no disease) requires a dominant or semidominant resistance (R) gene in the plant, and a corresponding avirulence (Avr) gene in the pathogen. Many plant/pathogen interactions are of this type. R genes are presumed to (a) enable plants to detect Avr-gene-specified pathogen molecules, (b) initiate signal transduction to activate defenses, and (c) have the capacity to evolve new R gene specificities rapidly. Isolation of R genes has revealed four main classes of R gene sequences whose products appear to activate a similar range of defense mechanisms. Discovery of the structure of R genes and R gene loci provides insight into R gene function and evolution, and should lead to novel strategies for disease control.
BASE FLIPPING
Authors: Roberts Richard J. , Cheng Xiaodong
Published: July 2002

Base flipping is the phenomenon whereby a base in normal B-DNA is swung completely out of the helix into an extrahelical position. It was discovered in 1994 when the first co-crystal structure was reported for a cytosine-5 DNA methyltransferase binding to DNA. Since then it has been shown to occur in many systems where enzymes need access to a DNA base to perform chemistry on it. Many DNA glycosylases that remove abnormal bases from DNA use this mechanism. This review describes systems known to use base flipping as well as many systems where it is likely to occur but has not yet been rigorously demonstrated. The mechanism and evolution of base flipping are also discussed.
Molecular Mechanisms of Neural Crest Formation
Authors: LaBonne Carole , Bronner-Fraser Marianne
Published: July 2002

▪ Abstract  The neural crest is a transient population of multipotent precursor cells named for its site of origin at the crest of the closing neural folds in vertebrate embryos. Following neural tube closure, these cells become migratory and populate diverse regions throughout the embryo where they give rise to most of the neurons and support cells of the peripheral nervous system (PNS), pigment cells, smooth muscle, craniofacial cartilage, and bone. Because of its remarkable ability to generate such diverse derivatives, the neural crest has fascinated developmental biologists for over one hundred years. A great deal has been learned about the migratory pathways neural crest cells follow and the signals that may trigger their differentiation, but until recently comparatively little was known about earlier steps in neural crest development. In the past few years progress has been made in understanding these earlier events, including how the precursors of these multipotent cells are specified in the early embryo and the mechanisms by which they become migratory. In this review, we first examine the mechanisms underlying neural crest induction, paying particular attention to a number of growth factor and transcription factor families that have been implicated in this process. We also discuss when and how the fate of neural crest precursors may diverge from those of nearby neural and epidermal populations. Finally, we review recent advances in our understanding of how neural crest cells become migratory and address the process of neural crest diversification.
The Myc/Max/Mad Network and the Transcriptional Control of Cell Behavior
Authors: Grandori Carla , Cowley Shaun M. , James Leonard P. , Eisenman Robert N.
Published: July 2002

▪ Abstract  The Myc/Max/Mad network comprises a group of transcription factors whose distinct interactions result in gene-specific transcriptional activation or repression. A great deal of research indicates that the functions of the network play roles in cell proliferation, differentiation, and death. In this review we focus on the Myc and Mad protein families and attempt to relate their biological functions to their transcriptional activities and gene targets. Both Myc and Mad, as well as the more recently described Mnt and Mga proteins, form heterodimers with Max, permitting binding to specific DNA sequences. These DNA-bound heterodimers recruit coactivator or corepressor complexes that generate alterations in chromatin structure, which in turn modulate transcription. Initial identification of target genes suggests that the network regulates genes involved in the cell cycle, growth, life span, and morphology. Because Myc and Mad proteins are expressed in response to diverse signaling pathways, the network can be viewed as a functional module which acts to convert environmental signals into specific gene-regulatory programs.
The Grasses: A Case Study in Macroevolution
Authors: Kellogg Elizabeth A.
Published: July 2002

▪ Abstract  Macroevolution in the grasses has often involved change in the position (heterotopy) of developmental programs, possibly via ectopic gene expression. Heterotopy apparently has been involved in the evolution of unique epidermal morphology in the grasses and their sister genus, Joinvillea; in the origin of the grass flower and possibly in the spikelet as well; in the formation of unisexual flowers in the panicoid grasses, and in the repeated origin of C4 photosynthesis. Change in timing of development (heterochrony) may explain the novel morphology of the grass embryo. Changes in the structure and size of the nuclear genome correlate with phylogenetically informative cytogenetic characteristics. Most of the 10,000 species of grasses evolved tens of millions of years after the common ancestor of the family, indicating that the origin of novel morphologies did not lead to immediate radiation.
JOINING ANDAVOIDANCEBEHAVIOR INNONSOCIALINSECTS
Authors: Prokopy Ronald J. , Roitberg Bernard D.
Published: July 2002

▪ Abstract  Groups of two or more consexual conspecific adults of many kinds of nonsocial insects have been observed to form at feeding, mating, ovipositional, or sheltering sites. Conversely, adults of these same insects have been observed to avoid joining consexual conspecifics (or their progeny) and to place themselves (or their progeny) at some distance that results in spacing. Examples from various taxa illustrate that mechanisms underlying joining or avoidance behavior differ among species, as do types of benefits and costs to individuals who decide to join or avoid others. Moreover, within a given species, the decision to join or avoid others can be affected markedly by the physiological and informational state of the individual and by contextual response thresholds to resource availability. Decisions that benefit the individual may or may not affect the group in terms of total reproductive output.
PARABOLIZED STABILITY EQUATIONS
Authors: Herbert Thorwald
Published: July 2002

▪ Abstract  Parabolized stability equations (PSE) have opened new avenues to the analysis of the streamwise growth of linear and nonlinear disturbances in slowly varying shear flows such as boundary layers, jets, and far wakes. Growth mechanisms include both algebraic transient growth and exponential growth through primary and higher instabilities. In contrast to the eigensolutions of traditional linear stability equations, PSE solutions incorporate inhomogeneous initial and boundary conditions as do numerical solutions of the Navier-Stokes equations, but they can be obtained at modest computational expense. PSE codes have developed into a convenient tool to analyze basic mechanisms in boundary-layer flows. The most important area of application, however, is the use of the PSE approach for transition analysis in aerodynamic design. Together with the adjoint linear problem, PSE methods promise improved design capabilities for laminar flow control systems.
BOUNDARY-LAYER RECEPTIVITY TO FREESTREAM DISTURBANCES
Authors: Saric William S. , Reed Helen L. , Kerschen Edward J.
Published: July 2002

▪ Abstract  The current understanding of boundary-layer receptivity to external acoustic and vortical disturbances is reviewed. Recent advances in theoretical modeling, numerical simulations, and experiments are discussed. It is shown that aspects of the theory have been validated and that the mechanisms by which freestream disturbances provide the initial conditions for unstable waves are better understood. Challenges remain, however, particularly with respect to freestream turbulence.
GENOME DOWNSIZING DURING CILIATE DEVELOPMENT: Nuclear Division of Labor through Chromosome Restructuring
Authors: Coyne Robert S. , Chalker Douglas L. , Yao Meng-Chao
Published: July 2002

▪ Abstract  The ciliated protozoa divide the labor of germline and somatic genetic functions between two distinct nuclei. The development of the somatic (macro-) nucleus from the germinal (micro-) nucleus occurs during sexual reproduction and involves large-scale, genetic reorganization including site-specific chromosome breakage and DNA deletion. This intriguing process has been extensively studied in Tetrahymena thermophila. Characterization of cis-acting sequences, putative protein factors, and possible reaction intermediates has begun to shed light on the underlying mechanisms of genome rearrangement. This article summarizes the current understanding of this phenomenon and discusses its origin and biological function. We postulate that ciliate nuclear restructuring serves to segregate the two essential functions of chromosomes: the transmission and expression of genetic information.
ON IMMUNOLOGICAL MEMORY
Authors: Zinkernagel Rolf M. , Bachmann Martin F. , Kündig Thomas M. , Oehen Stephan , Pirchet Hanspeter , Hengartner Hans
Published: July 2002

▪ Abstract  Immunological memory is a hallmark of the immune system. Evolution can teach us which effector arms of immunological memory are biologically relevant against which virus. Antibodies appear to be the critical protective mechanism against cytopathic viruses. Since these viruses cause cell damage and disease directly, particularly in the absence of an immune response, mothers protect their offspring during a critical immunoincompetent period (a consequence of MHC-restricted T cell recognition) by passive transfer of neutralizing antibodies. In contrast, CTL appear to be the crucial effector mechanism against noncytopathic viruses. Since MHC polymorphism has made vertical transmission of T cell memory impossible, immunoincompetent offspring are not, and need not be, protected against such noncytopathic viruses. During the primary response and again during secondary infection, the most important function of CTL is to eliminate noncytopathic viruses, which may otherwise cause lethal immunopathology. Increased precursor frequencies of B and T cells appear to remain in the host independent of antigen persistence. However, in order to protect against cytopathic viruses, memory B cells have to produce antibody to maintain protective elevated levels of antibody; B cell differentiation into plasma cells is driven by persisting antigen. Similarly, to protect against infection with a noncytopathic virus, CTL have to recirculate through peripheral organs. Activation and capacity to emigrate into solid tissues as well as cytolytic effector function are also dependent upon, and driven by, persisting antigen. Because no convincing evidence is available yet of the existence of identifiable B or T cells with specialized memory characteristics, the phenotype of immunological memory correlates best with antigen-driven activation of low frequency effector T cells and plasma cells.
ADJUVANT TREATMENT OF COLORECTAL CANCER
Authors: Saltz, MD Leonard B. , Kelsen, MD David P.
Published: July 2002

▪ Abstract  The adjuvant therapy of colorectal cancer has seen many important advances in recent years. Chemotherapy improves long-term disease-free survival rates in high-risk patients with resected colon cancer. Combined modality therapy, using surgery, radiation therapy, and chemotherapy, improves both local control and survival in patients with stage II and III rectal cancer. We examine in detail the data on which current recommendations for adjuvant treatments are based. We also review some of the more promising experimental approaches currently under investigation.
ACTIVATED PROTEIN C RESISTANCE DUE TO A COMMON FACTOR V GENE MUTATION IS A MAJOR RISK FACTOR FOR VENOUS THROMBOSIS
Authors: Zöller, MD B. , Hillarp, PhD A. , Berntorp, MD E. , Dahlbäck, MD B.
Published: July 2002

▪ Abstract  Inherited resistance to activated protein C (APC) was recently discovered to be a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. It is caused by a single point mutation in the gene for factor V, which predicts substitution of arginine (R) at position 506 with a glutamine (Q). Accordingly, the activated form of mutated factor V (FVa:Q506) is more slowly degraded by activated protein C than normal FVa (FVa:R506) is, resulting in hypercoagulability and a lifelong 5- to 10-fold increased risk of venous thrombosis. Previously known inherited hypercoagulable states, i.e. deficiencies of the anticoagulant proteins antithrombin III, protein S, and protein C, are found in fewer than 10–15% of thrombosis patients in western countries, whereas inherited APC resistance is present in 20–60% of such patients. The FV mutation is common in populations of Caucasian origin, with prevalences ranging from 1–15%, whereas it is not found in certain other ethnic groups such as Japanese and Chinese. The high prevalence of APC resistance, in combination with the availability of simple laboratory tests, will have a profound influence on the development of therapeutic and prophylactic regimens for thrombosis and will, it is hoped, result in a decreased incidence of thromboembolic events.
BREAKING AND ENTERING: Host Penetration by the Fungal Rice Blast Pathogen Magnaporthe grisea
Authors: Howard Richard J. , Valent Barbara
Published: July 2002

▪ Abstract  Fungal plant pathogens have evolved diverse mechanisms for penetrating into host plant tissue, ranging from entry through natural plant openings to various mechanisms of direct penetration through the outer surface. The filamentous fungus Magnaporthe grisea can cause disease on many species of the grass (Poaceae) family. The disease on rice, Rice Blast, is of enormous economic importance and biological interest. The mechanism used by this pathogen for breaching the formidable host surface barriers has been studied cytologically and genetically as a model for plant pathology, and represents a remarkably sophisticated achievment of nature. The single-celled appressorium of M. grisea acts as a vessel for the generation and application of perhaps the highest turgor pressures known. The fungus requires and utilizes melanin-derived, osmotically generated pressures estimated at 80 bars to drive an actin-rich cellular protuberance through the surface of a rice leaf or plastic coverslip.
Hydrophobins: Multipurpose Proteins
Authors: Wösten Han A. B.
Published: July 2002

▪ Abstract  Class I and class II hydrophobins are small secreted fungal proteins that play a role in a broad range of processes in the growth and development of filamentous fungi. For instance, they are involved in the formation of aerial structures and in the attachment of hyphae to hydrophobic surfaces. The mechanisms by which hydrophobins fulfill these functions are based on their property to self-assemble at hydrophilic-hydrophobic interfaces into a 10 nm-thin highly amphipathic film. Complementation studies have shown that class I hydrophobins belong to a closely related group of morphogenetic proteins, but that they have evolved to function at specific interfaces. Recent evidence indicates that hydrophobins do not only function by self-assembly. Monomeric hydrophobin has been implicated in cell-wall assembly, but the underlying mechanism is not yet clear. In addition, hydrophobin monomers could act as toxins and elicitors.
PAX-6IN DEVELOPMENT AND EVOLUTION
Authors: Callaerts Patrick , Halder Georg , Gehring Walter J.
Published: July 2002

▪ Abstract  Pax-6 is a member of the Pax gene class and encodes a protein containing a paired domain and a homeodomain. The molecular characterization of Pax-6 genes from species of different animal phyla and the analysis of Pax-6 function in the developing eyes and central nervous system of vertebrates, Drosophila melanogaster, and Caenorhabditis elegans suggest that Pax-6 homologues share conserved functions. In this review, we present recent data on the structural and functional characterization of Pax-6 homologues from species of different animal phyla. We discuss the implications of these findings for our understanding of the development and evolution of eyes and nervous systems.
FATTY ACID TRANSPORT ACROSS MEMBRANES: Relevance to Nutrition and Metabolic Pathology
Authors: Hajri Tahar , Abumrad Nada A.
Published: July 2002

▪ Abstract  Long-chain fatty acids are an important constituent of the diet and they contribute to a multitude of cellular pathways and functions. Uptake of long-chain fatty acids across plasma membranes is the first step in fatty acid utilization, and recent evidence supports an important regulatory role for this process. Although uptake of fatty acids involves two components, passive diffusion through the lipid bilayer and protein-facilitated transfer, the latter component appears to play the major role in mediating uptake by key tissues. Identification of several proteins as fatty acid transporters, and emerging evidence from genetically altered animal models for some of these proteins, has contributed significant insight towards understanding the limiting role of transport in the regulation of fatty acid utilization. We are also beginning to better appreciate how disturbances in fatty acid utilization influence general metabolism and contribute to metabolic pathology.
MALNUTRITION AND POVERTY
Authors: Peña Manuel , Bacallao Jorge
Published: July 2002

▪ Abstract  This paper is an attempt to discuss the problem of malnutrition within the framework of the global need for development and the challenges posed by the trends of neoliberalism and globalization. We argue that there is a two-way link between poverty and health in which nutrition plays an important role both as an active and as a mediating factor. Key concepts are exposed and expanded: (a) Development per se does not ensure better health; (b) unequal distribution of income has an independent effect on health indicators after adjusting for total income; (c) improving health can make an important contribution to reducing poverty; (d ) improving nutrition throughout the whole life course is an indispensable strategy for better health; (e) obesity has to be included amongst the most critical health problems, has different traits, and presents with different challenges in the developing world and in the industrialized countries.
The Changing Face of the Na+/H+ Exchanger, NHE1: Structure, Regulation, and Cellular Actions
Authors: Putney L. K. , Denker S. P. , Barber D. L.
Published: July 2002

The NHE family of ion exchangers includes six isoforms (NHE1–NHE6) that function in an electroneutral exchange of intracellular H+ for extracellular Na+. This review focuses on the only ubiquitously expressed isoform, NHE1, which is localized at the plasma membrane where it plays a critical role in intracellular pH (pHi) and cell volume homeostasis. All NHE isoforms share a similar topology: an N-terminus of 12 transmembrane (TM) α-helices that collectively function in ion exchange, and a C-terminal cytoplasmic regulatory domain that modulates transport activity by the TM domain. Extracellular signals, mediated by diverse classes of cell-surface receptors, regulate NHE1 activity through distinct signaling networks that converge to directly modify the C-terminal regulatory domain. Modifications in the C-terminus, including phosphorylation and the binding of regulatory proteins, control transport activity by altering the affinity of the TM domain for intracellular H+. Recently, it was determined that NHE1 also functions as a membrane anchor for the actin-based cytoskeleton, independently of its role in ion translocation. Through its effects on pHi homeostasis, cell volume, and the actin cortical network, NHE1 regulates a number of cell behaviors, including adhesion, shape determination, migration, and proliferation.
UNDERSTANDING NMR CHEMICAL SHIFTS
Authors: Jameson Cynthia J.
Published: July 2002

▪ Abstract  The NMR chemical shift serves as a paradigm for molecular electronic properties. We consider the factors that determine the general magnitudes of the shifts, the state of the art in theoretical calculations, the nature of the shielding tensor, and the multidimensional shielding surface that describes the variation of the shielding with nuclear positions. We also examine the nature of the intermolecular shielding surface as a general example of a supermolecule property surface. The observed chemical shift in the zero-pressure limit is determined not only by the value of the shielding at the equilibrium geometry, but the dynamic average over the multidimensional shielding surface during rotation and vibration of the molecule. In the gas, solution, or adsorbed phase it is an average of the intermolecular shielding surface over all the configurations of the molecule with its neighbors. The temperature dependence of the chemical shift in the isolated molecule, the changes upon isotopic substitution, the changes with environment, are well characterized experimentally so that quantum mechanical descriptions of electronic structure and theories related to dynamics averaging of any electronic property can be subjected to stringent test.
Multidimensional Femtosecond Correlation Spectroscopies of Electronic and Vibrational Excitations
Authors: Mukamel Shaul
Published: July 2002

Femtosecond visible and infrared analogues of multiple-pulse nuclear magnetic resonance techniques provide novel snapshot probes into the structure and electronic and vibrational dynamics of complex molecular assemblies such as photosynthetic antennae, proteins, and hydrogen-bonded liquids. A classical-oscillator description of these spectroscopies in terms of interacting quasiparticles (rather than transitions among global eigenstates) is developed and sets the stage for designing new pulse sequences and inverting the multidimensional signals to yield molecular structures. Considerable computational advantages and a clear physical insight into the origin of the response and the relevant coherence sizes are provided by a real-space analysis of the underlying coherence-transfer pathways in Liouville space.
CONTROVERSIAL ISSUES IN VERTEBRATE OLFACTORY TRANSDUCTION
Authors: Gold Geoffrey H.
Published: July 2002

▪ Abstract  A number of controversial issues in olfactory transduction are discussed including the matter of multiple transduction pathways, with a new experiment proposed. Evidence is reviewed concerning the fact that cyclic AMP is the only pathway mediating olfactory transduction. Two knockout mice have been produced: a knockout for a cyclic nucleotide-gated channel and a Golfknockout. The results obtained with both mice are consistent with cyclic AMP being the only second messenger. The evidence for gaseous second channel messengers is also reviewed. Slow gating kinetics of the cyclic nucleotide-gated channel and the detection of single-odorant molecules are reviewed. A new phenomenon in which odorants can block odorant responses is discussed.
Genetic Dissection of Cardiac Growth Control Pathways
Authors: MacLellan W. Robb , Schneider Michael D.
Published: July 2002

▪ Abstract  Cardiac muscle cells exhibit two related but distinct modes of growth that are highly regulated during development and disease. Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle irreversibly soon after birth, following which the predominant form of growth shifts from hyperplastic to hypertrophic. Much research has focused on identifying the candidate mitogens, hypertrophic agonists, and signaling pathways that mediate these processes in isolated cells. What drives the proliferative growth of embryonic myocardium in vivo and the mechanisms by which adult cardiac myocytes hypertrophy in vivo are less clear. Efforts to answer these questions have benefited from rapid progress made in techniques to manipulate the murine genome. Complementary technologies for gain- and loss-of-function now permit a mutational analysis of these growth control pathways in vivo in the intact heart. These studies have confirmed the importance of suspected pathways, have implicated unexpected pathways as well, and have led to new paradigms for the control of cardiac growth.
The Human Language Faculty as an Organ
Authors: Anderson Stephen R. , Lightfoot David W.
Published: July 2002

▪ Abstract  Developments in the study of language and cognition give increasing credibility to the view that human knowledge of natural language results from—and is made possible by—a biologically determined capacity specific both to this domain and to our species. The functional properties of this capacity develop along a regular maturational path, such that it seems more appropriate to speak of knowledge of our own language as growing rather than as being learned. That our learning of language results from a specific innate capacity rather than by general mechanisms of induction is supported by the extent to which we can be shown to know things that we could not have learned from observation of any plausible available teaching. The domainspecificity of the language faculty is supported by the many dissociations that can be observed between control of language structure and other cognitive functions. Finally, the species-specificity of the human language faculty is supported by the observation that (absent severe pathology) every human child exposed in even limited ways to the triggering experience of linguistic data develops a full, rich capacity that is essentially homogeneous with that of the surrounding community. Efforts to teach human language to other species, however, have uniformly failed. These considerations make it plausible that human language arises in biologically based ways that are quite comparable to those directing other aspects of the structure of the organism. The language organ, in this sense, can be interpreted in a functional sense, and not as implying an anatomical location comparable to that of, say, the kidney.
Mycosporine-Like Amino Acids and Related Gadusols: Biosynthesis, Accumulation, and UV-Protective Functions in Aquatic Organisms
Authors: Shick J. Malcolm , Dunlap Walter C.
Published: July 2002

▪ Abstract  Organisms living in clear, shallow water are exposed to the damaging wavelengths of solar ultraviolet radiation (UVR) coincident with the longer wavelengths of photosynthetically available radiation (PAR) also necessary for vision. With the general exception of bacteria, taxonomically diverse marine and freshwater organisms have evolved the capacity to synthesize or accumulate UV-absorbing mycosporine-like amino acids (MAAs), presumably for protection against environmental UVR. This review highlights the evidence for this UV-protective role while also considering other attributed functions, including reproductive and osmotic regulation and vision. Probing the regulation and biosynthesis of MAAs provides insight to the physiological evolution and utility of UV protection and of biochemically associated antioxidant defenses.
ROOT CORTEX—THE FINAL FRONTIER FOR THE BIOCONTROL OF ROOT-ROT WITH FUNGAL ANTAGONISTS: A Case Study on a Sterile Red Fungus
Authors: Sivasithamparam K.
Published: July 2002

▪ Abstract  Root cortices remain as the last frontier for the biocontrol agents to protect the vascular elements from the invader, where the virulent pathogen has breached the bulk soil, rhizosphere, and rhizoplane. Root cortices are commonly colonized by a variety of soilborne fungi. Many nonmycorrhizal biocontrol fungi that occupy the rhizosphere appear to extend their activity into the live cells of the cortex. It has been proposed that the occupation of the cortices by biocontrol fungi introduced on seed at sowing could extend their activity in time and space. The biology and ecology of such fungi with parasitic competency to colonize live cortical cells are discussed in relation to a case study involving a sterile cortical fungus.