bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal histogram matching by monotone gray level transformation
Authors: Chang Shi-Kuo , Wong Yin-Wah
Published: July 2002

This paper investigates the problem of optimal histogram matching using monotone gray level transformation, which always assigns all picture points of a given gray level
i
to another gray level
T
(
i
) such that if
i
≥
j
, then
T
(
i
) ≥
T
(
j
). The objective is to find a transformed digital picture of a given picture such that the sum of absolute errors between the gray level histogram of the transformed picture and that of a reference picture is minimized. This is equivalent to placing
k
1 linearly ordered objects of different sizes one by one into
k
2 linearly ordered boxes of assorted sizes, such that the accumulated error of space underpacked or overpacked in the boxes is minimized; the placement function is monotonic, which ensures a polynomial time solution to this problem. A tree search algorithm for optimal histogram matching is presented which has time complexity
O
(
k
1 ×
k
2). If the monotone property is dropped, then the problem becomes
NP
-complete, even if it is restricted to
k
2 = 2.
An analysis of inline substitution for a structured programming language
Authors: Scheifler Robert W.
Published: July 2002

An optimization technique known as inline substitution is analyzed. The optimization consists of replacing a procedure invocation by a modified copy of the procedure body. The general problem of using inline substitution to minimize execution time subject to size constraints is formulated, and an approximate algorithmic solution is proposed. The algorithm depends on run-time statistics about the program to be optimized. Preliminary results for the CLU structured programming language indicate that, in programs with a low degree of recursion, over 90 percent of all procedure calls can be eliminated, with little increase in the size of compiled code and a small savings in execution time. Other conclusions based on these results are also presented.
Sampling from the gamma distribution on a computer
Authors: Fishman George S.
Published: July 2002

This paper describes a method of generating gamma variates that appears to be less costly than Wallace's recently suggested method. For large shape parameter
α
; the cost of computation is proportional to √
α
, whereas Wallace's method is proportional to
α
. Experimentation by Robinson and Lewis indicates that for small
α
the method suggested here also dominates methods recently suggested by Dieter and Ahrens, albeit those methods dominate for large
α
. The method suggested here uses the rejection technique.
An insertion technique for one-sided height-balanced trees
Authors: Hirschberg D. S.
Published: July 2002

A restriction on height-balanced binary trees is presented. It is seen that this restriction reduces the extra memory requirements by half (from two extra bits per node to one) and maintains fast search capabilities at a cost of increased time requirements for inserting new nodes.
Dynamic document processing
Authors: Salton Gerard
Published: July 2002

The current role of computers in automatic document processing is briefly outlined, and some reasons are given why the early promise of library automation and of the mechanization of documentation processes has not been fulfilled.

A new dynamic document environment is then outlined in which clustered files are searched and information is retrieved following an interactive user-controlled search process. Methods are described for an automatic query modification based on user needs, and for a continuous reorganization of the stored information as a function of earlier file processing and of normal collection growth. The proposed procedures provide powerful tools for information retrieval and for the control of dynamic library collections in which new items are continually added and ones are retired.
Algorithm and bound for the greatest common divisor of
n
integers
Authors: Bradley Gordon H.
Published: July 2002

A new version of the Euclidean algorithm for finding the greatest common divisor of
n
integers

a
i

and multipliers

x
i

such that gcd =
x
1
a
1
+ ··· +

x
n
a
n

is presented. The number of arithmetic operations and the number of storage locations are linear in
n
. A theorem of Lamé that gives a bound for the number of iterations of the Euclidean algorithm for two integers is extended to the case of
n
integers. An algorithm to construct a minimal set of multipliers is presented. A Fortran program for the algorithm appears as
Comm. ACM
Algorithm 386.
Computation of

J
n
(x)

by numerical integration
Authors: Stroud A. H. , Kohli J. P.
Published: July 2002

It is shown to be practical to compute

J
n

(
x
) by numerical integration of its integral representation using the trapezoidal rule. The error in this approximation was studied empirically.
An online editor
Authors: Deutsch L. Peter , Lampson Butler W.
Published: July 2002

An online, interactive system for text editing is described in detail, with remarks on the theoretical and experimental justification for its form. Emphasis throughout the system is on providing maximum convenience and power for the user. Notable features are its ability to handle any piece of text, the content-searching facility, and the character-by-character editing operations. The editor can be programmed to a limited extent.
A precision- and range-independent tool for testing floating-point arithmetric I
Authors: Verdonk Bridgitte , Cuyt Annie , Verschaeren Dennis
Published: July 2002

This paper introduces a precision- and range-independent tool for testing the compliance of hardware or software implementations of (multiprecision) floating-point arithmetic with the principles of the IEEE standards 754 and 854. The tool consists of a driver program, offering many options to test only specific aspects of the IEEE standards, and a large set of test vectors, encoded in a precision-independent syntax to allow the testing of basic and extended hardware formats as well as multiprecision floating-point implementations. The suite of test vectors stems on one hand from the integration and fully precision- and range-independent generalization of existing hardware test sets, and on the other hand from the systematic testing of exact rounding for all combinations of round and sticky bits that can occur. The former constitutes only 50% of the resulting test set. In the latter we especially focus on hard-to-round cases. In addition, the test suite implicitly tests properties of floating-point operations, following the idea of Paranoia, and it reports which of the three IEEE-compliant underflow mechanisms is used by the floating-point implementation under consideration. We also chech whether that underflow mechanism is used consistently. The tool is backward compatible with the UCBTEST package and with Coonen's test syntax.
Iterative aggregation/disaggregation techniques for nearly uncoupled markov chains
Authors: Cao Wei-Lu , Stewart William J.
Published: July 2002

Iterative aggregation/disaggregation methods provide an efficient approach for computing the stationary probability vector of nearly uncoupled (also known as nearly completely decomposable) Markov chains. Three such methods that have appeared in the literature recently are considered and their similarities and differences are outlined. Specifically, it is shown that the method of Takahashi corresponds to a modified block Gauss-Seidel step and aggregation, whereas that of Vantilborgh corresponds to a modified block Jacobi step and aggregation. The third method, that of Koury et al., is equivalent to a standard block Gauss-Seidel step and iteration. For each of these methods, a lemma is established, which shows that the unique fixed point of the iterative scheme is the left eigenvector corresponding to the dominant unit eigenvalue of the stochastic transition probability matrix. In addition, conditions are established for the convergence of the first two of these methods; convergence conditions for the third having already been established by Stewart et al. All three methods are shown to have the same asymptotic rate of convergence.
Reasoning about code mobility with mobile UNITY
Authors: Picco Gian Pietro , Roman Gruia-Catalin , McCann Peter J.
Published: July 2002

Advancements in network technology have led to the emergence of new computing paradigms that challenge established programming practices by employing weak forms of consistency and dynamic forms of binding. Code mobility, for instance, allows for invocation-time binding between a code fragment and the location where it executes. Similarly, mobile computing allows hosts (and the software they execute) to alter their physical location. Despite apparent similarities, the two paradigms are distinct in their treatment of location and movement. This paper seeks to uncover a common foundation for the two paradigms by exploring the manner in which stereotypical forms of code mobility can be expressed in a programming notation developed for mobile computing. Several solutions to a distributed simulation problem are used to illustrate the modeling strategy and the ability to construct assertional-style proofs for programs that employ code mobility.
A relational approach to monitoring complex systems
Authors: Snodgrass Richard
Published: July 2002

Monitoring is an essential part of many program development tools, and plays a central role in debugging, optimization, status reporting, and reconfiguration. Traditional monitoring techniques are inadequate when monitoring complex systems such as multiprocessors or distributed systems. A new approach is described in which a historical database forms the conceptual basis for the information processed by the monitor. This approach permits advances in specifying the low-level data collection, specifying the analysis of the collected data, performing the analysis, and displaying the results. Two prototype implementations demonstrate the feasibility of the approach.
Pattern formation and chaos in networks
Authors: Pickover Clifford A.
Published: July 2002

Chaos theory involves the study of how complicated behavior can arise in systems that are based on simple rules, and how minute changes in the input of a system can lead to great differences in the output. Using computer graphics, the dynamic behavior of chaos-producing networks is explored, and convergence maps reveal a visually striking and intricate class of displayable objects.
Computer puppetry
Authors: Shin Hyun Joon , Lee Jehee , Shin Sung Yong , Gleicher Michael
Published: July 2002

Computer puppetry maps the movements of a performer to an animated character in real-time. In this article, we provide a comprehensive solution to the problem of transferring the observations of the motion capture sensors to an animated character whose size and proportion may be different from the performer's. Our goal is to map as many of the
important
aspects of the motion to the target character as possible, while meeting the online, real-time demands of computer puppetry. We adopt a Kalman filter scheme that addresses motion capture noise issues in this setting. We provide the notion of dynamic importance of an end-effector that allows us to determine what aspects of the performance must be kept in the resulting motion. We introduce a novel inverse kinematics solver that realizes these important aspects within tight real-time constraints. Our approach is demonstrated by its application to broadcast television performances.
Self-reconfiguring robots
Authors: Rus Daniela , Butler Zack , Kotay Keith , Vona Marsette
Published: July 2002

Mimicking the adaptability of living biological cells, robot modules will reconfigure themselves toward a common purpose within the limits imposed by the local environment.
Fault tolerance under UNIX
Authors: Borg Anita , Blau Wolfgang , Graetsch Wolfgang , Herrmann Ferdinand , Oberle Wolfgang
Published: July 2002

The initial design for a distributed, fault-tolerant version of UNIX based on three-way atomic message transmission was presented in an earlier paper [3]. The implementation effort then moved from Auragen Systems
1
to Nixdorf Computer where it was completed. This paper describes the working system, now known as the TARGON/32.

The original design left open questions in at least two areas: fault tolerance for server processes and recovery after a crash were briefly and inaccurately sketched, rebackup after recovery was not discussed at all. The fundamental design involving three-way message transmission has remained unchanged. However, in addition to important changes in the implementation, server backup has been redesigned and is now more consistent with that of normal user processes. Recovery and rebackup have been completed in a less centralized and thus more efficient manner than previously envisioned.

In this paper we review important aspects of the original design and note how the implementation differs from our original ideas. We then focus on the backup and recovery for server processes and the changes and additions in the design and implementation of recovery and rebackup.
Novice mistakes: are the folk wisdoms correct?
Authors: Spohrer James C. , Soloway Elliot
Published: July 2002

An evaluation of two folk wisdoms serves to elucidate the underlying or "deep-structure" reasons for novice errors.
On the minimal synchronism needed for distributed consensus
Authors: Dolev Danny , Dwork Cynthia , Stockmeyer Larry
Published: July 2002

Reaching agreement is a primitive of distributed computing. Whereas this poses no problem in an ideal, failure-free environment, it imposes certain constraints on the capabilities of an actual system: A system is viable only if it permits the existence of consensus protocols tolerant to some number of failures. Fischer et al. have shown that in a completely asynchronous model, even one failure cannot be tolerated. In this paper their work is extended: Several critical system parameters, including various synchrony conditions, are identified and how varying these affects the number of faults that can be tolerated is examined. The proofs expose general heuristic principles that explain why consensus is possible in certain models but not possible in others.
The multifrontal method and paging in sparse Cholesky factorization
Authors: Liu Joseph W. H.
Published: July 2002

In this paper, we show that the multifrontal method can have significant advantage over the conventional sparse column-Cholesky scheme on a paged virtual memory system. A more than tenfold reduction in paging activities can be achieved, which saves as much as 20 percent in factorization time. We also introduce a hybrid sparse factorization method, which uses a mixture of column-Cholesky and submatrix-Cholesky operations. By switching to the use of frontal matrices from column-Cholesky operations at appropriate columns, we demonstrate that the proposed hybrid scheme has an advantage over the sparse column-Cholesky method in reducing paging activities and over the multifrontal method in its adaptability to the amount of available working storage.
Performance evaluation of programs for the error and complementary error functions
Authors: Cody W. J.
Published: July 2002

This paper presents methods for performance evaluation of computer programs for the functions erf(
x
), erfc(
x
), and e

x
2

erfc(
x
). Accuracy estimates are based on comparisons using power series expansions and an expansion in the repeated integrals of erfc(
x
). Some suggestions for checking robustness are also given. Details of a specific implementation of a test program are included.
On compile-time query optimization in deductive databases by means of static filtering
Authors: Kifer Michael , Lozinskii Eliezer L.
Published: July 2002

We extend the query optimization techniques known as algebric manipulations with relational expressions [48] to work with deductive databases. In particular, we propose a method for moving data-independent selections and projections into recursive axioms, which extends all other known techniques for performing that task [2, 3, 9, 18, 20]. We also show that, in a well-defined sense, our algorithm is optimal among the algorithms that propagate data-independent selections through recursion.
Diffusion in computing networks: the case of BITNET
Authors: Gurbaxani Vijay
Published: July 2002

Using BITNET as a model, the author examines the adoption pattern of computing networks from the perspectives of innovation diffusion theory and economics.
Life History Traits in Humans: Theory and Empirical Studies
Authors: Hill Kim , Kaplan Hillard
Published: July 2002

▪ Abstract  Life history theory offers evolutionary explanations for the timing of life events, with a particular focus on age-schedules of fertility and mortality and growth. Traditional models examine trade-offs between current and future reproduction and quality versus quantity of offspring. These models can be used to understand questions concerning time of gestation, age of weaning, juvenile mortality profiles, age at maturation, adult body size, fertility rates, senescence, menopause, and the length of the life span. The trajectory of energy acquisition and its allocations is also an important part of life history theory. Modifications of these models have been developed to examine the period of learning, postweaning parental investment, and patterns of development. In this article, we combine energetic and demographic approaches in order to examine the human life course from an optimality perspective. The evolved life history solves related problems across two generations. The first set of decisions concerns how to maximize own lifetime net energy production that can be used for reproduction. The second set of decisions concerns how to maximize total offspring energy production (summed over all offspring).
Biodiversity Prospecting: Lessons and Prospects
Authors: Moran Katy , King Steven R. , Carlson Thomas J.
Published: July 2002

▪ Abstract  Introduction of the U.N. Convention on Biological Diversity and the growth of biotechnology processes have recently led anthropologists into the rapidly moving, ethically and philosophically challenging field of bioprospecting or exploring biological diversity for commercially valuable genetic and biochemical resources. Is bioprospecting an innovative mechanism that will (a) help produce new therapeutics and preserve traditional medical systems, (b) conserve both biological and cultural diversity by demonstrating their medical, economic, and social values, and (c) bring biotechnology and other benefits to biodiversity-rich but technology poor countries? Or is bioprospecting yet another form of colonialism—“bioimperialism”—wherein the North rips off the South's resources and intellectual property rights? This article reviews the current literature on bioprospecting that lies somewhere between current polemics and calls for more anthropological research into the bioprospecting process.
STRUCTURE AND FUNCTION IN GroEL-MEDIATED PROTEIN FOLDING
Authors: Sigler Paul B. , Xu Zhaohui , Rye Hays S. , Burston Steven G. , Fenton Wayne A. , Horwich Arthur L.
Published: July 2002

Recent structural and biochemical investigations have come together to allow a better understanding of the mechanism of chaperonin (GroEL, Hsp60)–mediated protein folding, the final step in the accurate expression of genetic information. Major, asymmetric conformational changes in the GroEL double toroid accompany binding of ATP and the cochaperonin GroES. When a nonnative polypeptide, bound to one of the GroEL rings, is encapsulated by GroES to form a cis ternary complex, these changes drive the polypeptide into the sequestered cavity and initiate its folding. ATP hydrolysis in the cis ring primes release of the products, and ATP binding in the trans ring then disrupts the cis complex. This process allows the polypeptide to achieve its final native state, if folding was completed, or to recycle to another chaperonin molecule, if the folding process did not result in a form committed to the native state.
ECOLOGY: A Personal History
Authors: Bormann F. H.
Published: July 2002

[Figure: see text]

▪ Abstract  FH Bormann, based on personal experience, recalls 55 years of association with the field of ecology, including the forces that led him into the field, research, development of the Hubbard Brook Ecosystem Study, and clashes between ecology, policy, and politics. He concludes with thoughts on humankind's search for the quality of life and sustainability.
METHODS FOR ATTRIBUTING AMBIENT AIR POLLUTANTS TO EMISSION SOURCES
Authors: Blanchard Charles L.
Published: July 2002

▪ Abstract  Six methods for attributing ambient pollutants to emission sources are reviewed: emissions analysis, trend analysis, tracer studies, trajectory analysis, receptor modeling, and dispersion modeling. The ranges of applicability, types of information provided, limitations, performance capabilities, and areas of active research of the different methods are compared. For primary, nonreactive pollutants whose effects of concern occur on a global scale, an accounting of emissions rates by source type and location largely characterizes source contributions. For other pollutants or smaller spatial scales, accurate estimates of emissions are needed for identifying the emissions reduction potentials of possible control measures and as inputs to dispersion models. Emission levels are frequently known with factor-of-two accuracy or worse, and improved estimates are needed for dispersion modeling. The analysis of regional or urban-scale trends in emissions and ambient pollutant concentrations can provide qualitative information on source contributions, but quantitative results are limited by the confounding influence of variations in meteorology and uncertainties in the areas over which emissions affect concentrations. Tracer studies are useful for quantifying dispersion characteristics of plumes, qualitatively characterizing transport directions, and providing empirical data for evaluating trajectory and dispersion models. Data are usually temporally limited to a short study period, typically do not provide information on vertical pollutant distributions, and are most applicable to the transport of primary, nonreactive pollutants. Trajectory analyses are routinely used to estimate atmospheric transport directions. Trajectory errors of about 20% of travel distance are considered typical of the better models and data sets. Receptor models use measurements of ambient pollutant concentrations to quantify the contributions of different source types to primary particulate matter or volatile organic compounds, or to characterize source-region contributions to a single pollutant. Accuracy rates of ∼30% are often achieved when quantifying the contributions from different types of emission sources. Dispersion models are well-suited for estimating quantitative source-receptor relationships, as the effects of individual emission sources or source regions can be studied. Lagrangian and Gaussian dispersion models are computationally efficient and can simulate the transport of nonreactive primary or linear secondary species. Eulerian models are computationally intensive but lend themselves to the simulation of nonlinear chemistry. Careful evaluation of modeling accuracy is needed for a model application to fulfill its potential for source attribution. Accuracy can be evaluated through a combination of performance evaluation, sensitivity analysis, diagnostic evaluation, and corroborating analyses.
THE ROLE OF DNA METHYLATION IN CANCER GENETICS AND EPIGENETICS
Authors: Laird Peter W. , Jaenisch Rudolf
Published: July 2002

▪ Abstract  The past few years have seen a wider acceptance of a role for DNA methylation in cancer. This can be attributed to three developments. First, the documentation of the over-representation of mutations at CpG dinucleotides has convincingly implicated DNA methylation in the generation of oncogenic point mutations. The second important advance has been the demonstration of epigenetic silencing of tumor suppressor genes by DNA methylation. The third development has been the utilization of experimental methods to manipulate DNA methylation levels. These studies demonstrate that DNA methylation changes in cancer cells are not mere by-products of malignant transformation, but can play an instrumental role in the cancer process. It seems clear that DNA methylation plays a variety of roles in different cancer types and probably at different stages of oncogenesis. DNA methylation is intricately involved in a wide diversity of cellular processes. Likewise, it appears to exert its influence on the cancer process through a diverse array of mechanisms. It is our task not only to identify these mechanisms, but to determine their relative importance for each stage and type of cancer. Our hope then will be to translate that knowledge into clinical applications.
GENETIC ANALYSIS OF THE MITOTIC SPINDLE
Authors: Hoyt M. Andrew , Geiser John R.
Published: July 2002

▪ Abstract  Much of our understanding of the molecular basis of mitotic spindle function has been achieved within the past decade. Studies utilizing genetically tractable organisms have made important contributions to this field and these studies form the basis of this review. We focus upon three areas of spindle research: spindle poles, centromeres, and spindle motors. The structure and duplication mechanisms of spindle poles are considered as well as their roles in organizing spindle microtubules. Centromeres vary considerably in their size and complexity. We describe recent progress in our understanding of the relatively simple centromeres of the yeast Saccharomyces cerevisiae and the complex centromeres that are more typical of eukaryotic cells. Microtubule-based motor proteins that generate the characteristic spindle movements have been identified in recent years and can be grouped into families defined by conserved primary sequence and mitotic function.
GENETIC SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Vyse T. J. , Kotzin B. L.
Published: July 2002

▪ Abstract  Considerable evidence suggests that the development of systemic lupus erythematosus (SLE) has a strong genetic basis. Recent studies have emphasized that this disease, like other autoimmune diseases, is a complex genetic trait with contributions from major histocompatibility complex (MHC) genes and multiple non-MHC genes. Etiologic genes in these disorders determine susceptibility, and no particular gene is necessary or sufficient for disease expression. Studies of murine models of lupus have provided important insight into the immunopathogenesis of IgG autoantibody production and lupus nephritis, and genetic analyses of these mice overcome certain obstacles encountered when studying patients. Genome-wide linkage studies of different crosses have mapped the position of at least 12 non-MHC disease-susceptibility loci in the New Zealand hybrid model of lupus. Although the identity of the actual genes is currently unknown, recent studies have begun to characterize how these genetic contributions may function in the autoimmune process, especially in terms of their role in autoantibody production. Studies of MHC gene contributions in New Zealand mice have shown that heterozygosity for particular haplotypes greatly increases pathogenic autoantibody production and the incidence of severe nephritis. The mechanism for this effect appears to be genetically complex. Studies in human SLE have mostly focused on the association of disease with alleles of immunologically relevant genes, especially in the MHC. Associations with various complement component deficiencies and an allele of a particular Fcγ receptor gene (FCGR2A) also have been described. In a diversion from previous association studies, a recent directed linkage analysis of sibpairs with SLE was based on mapping studies in murine lupus and may be an important step toward identifying a new disease-susceptibility gene in patients. Since the genes that predispose to autoimmunity are probably related to key events in pathogenesis, their identification in patients and murine models will almost certainly provide important insight into the breakdown of immunological self-tolerance and the cause of autoimmune disease.
HYPERTENSION IN THE ELDERLY
Authors: Kaplan, M.D Norman M.
Published: July 2002

▪ Abstract  Elderly people have a very high prevalence of hypertension, which markedly increases their risk for cardiovascular morbidity and mortality. Convincing evidence demonstrates the effectiveness of antihypertensive therapy in reducing these risks significantly. With appropriate caution, most elderly hypertensives can be treated and thereby protected from many of the debilities of old age.
MANAGEMENT OF EARLY NEPHROPATHY IN DIABETIC PATIENTS
Authors: Mogensen, M.D Carl Erik
Published: July 2002

▪ Abstract  Diabetic patients go through several stages of renal disease, moving from normo- to micro- to macroalbuminuria. Good metabolic control can prevent or postpone the development of microalbuminuria, the earliest sign of diabetic renal disease. Thus, efforts should focus on obtaining the best possible control before the onset of microalbuninuria. In patients with microalbuminuria, blood pressure starts to increase, and early antihypertensive treatment becomes important. Good glycemic control may be difficult to achieve. With overt nephropathy, defined as clinical proteinuria, a relentless decline in glomerular filtration rate (GFR) occurs unless patients are carefully treated with antihypertensive agents. Protein restriction may also be necessary, but a clear beneficial effect of optimized diabetes care is difficult to document. Early screening is recommended, with an emphasis on testing for albuminuria, including microalbuminuria, along with careful control of blood pressure.
The Expanding Pharmacopoeia for Bipolar Disorder
Authors: Mitchell Philip B. , Malhi Gin S.
Published: July 2002

▪ Abstract  Over the past decade, the number of treatments available for bipolar disorder has undergone an extraordinary expansion. In that period, valproate and olanzapine have received regulatory approval in the United States for the acute treatment of mania, and carbamazepine has been indicated for this condition in many other countries. In addition to those agents, a number of other anticonvulsants (in particular lamotrigine, gabapentin, and topiramate) are in trials, as are the atypical antipsychotics clozapine and risperidone, and other novel compounds. This article critically reviews the evidence from controlled trials of these proposed “mood stabilizers,” highlighting the strengths and limitations of the data for each compound. A major challenge to the field is the capacity to prove the prophylactic properties of agents for which effectiveness in acute mania and/or bipolar depression has been demonstrated. Finally, as the mechanisms of agents such as lithium are now becoming apparent, and the possibility of understanding the molecular defects underpinning the condition is no longer highly fanciful, the prospect of targeted therapies is considered feasible by both academia and the pharmaceutical industry.
Interim Report on Genomics of Escherichia Coli
Authors: Riley M. , Serres M. H.
Published: July 2002

▪ Abstract  We present a summary of recent progress in understanding Escherichia coli K-12 gene and protein functions. New information has come both from classical biological experimentation and from using the analytical tools of functional genomics. The content of the E. coli genome can clearly be seen to contain elements acquired by horizontal transfer. Nevertheless, there is probably a large, stable core of >3500 genes that are shared among all E. coli strains. The gene-enzyme relationship is examined, and, in many cases, it exhibits complexity beyond a simple one-to-one relationship. Also, the E. coli genome can now be seen to contain many multiple enzymes that carry out the same or closely similar reactions. Some are similar in sequence and may share common ancestry; some are not. We discuss the concept of a minimal genome as being variable among organisms and obligatorily linked to their life styles and defined environmental conditions. We also address classification of functions of gene products and avenues of insight into the history of protein evolution.
Novel Thiols of Prokaryotes
Authors: Fahey Robert C.
Published: July 2002

▪ Abstract  Glutathione metabolism is associated with oxygenic cyanobacteria and the oxygen-utilizing purple bacteria, but is absent in many other prokaryotes. This review focuses on novel thiols found in those bacteria lacking glutathione. Included are glutathione amide and its perthiol, produced by phototrophic purple sulfur bacteria and apparently involved in their sulfide metabolism. Among archaebacteria, coenzyme M (2-mercaptoethanesulfonic acid) and coenzyme B (7-mercaptoheptanoylthreonine phosphate) play central roles in the anaerobic production of CH4 and associated energy conversion by methanogens, whereas the major thiol in the aerobic phototrophic halobacteria is γ-glutamylcysteine. The highly aerobic actinomycetes produce mycothiol, a conjugate of N-acetylcysteine with a pseudodisaccharide of glucosamine and myo-inositol, AcCys-GlcNα(1 → 1)Ins, which appears to play an antioxidant role similar to glutathione. Ergothioneine, also produced by actinomycetes, remains a mystery despite many years of study. Available data on the biosynthesis and metabolism of these and other novel thiols is summarized and key areas for additional study are identified.
Homology-Dependent Gene Silencing Mechanisms in Fungi
Authors: Cogoni Carlo
Published: July 2002

▪ Abstract  Homology-dependent gene silencing (HDGS) is a ubiquitous phenomenon among fungi, plants, and animals. Gene silencing can be triggered and can affect artificially introduced nucleic acid molecules, both DNA and RNA, and/or can act on endogenous duplicated sequences. Although the various HDGS phenomena may be related each other, probably deriving from an ancestral defense mechanism, relevant differences do exist between different HDGS mechanisms. Especially in fungi, a variety of HDGS phenomena have been uncovered during the past 10 years: Gene inactivation of duplicated sequences can be achieved either through DNA-methylation and block of transcription or through sequence-specific degradation of mRNA. Moreover, duplicated sequences can also be specifically mutagenized. Studying HDGS in fungi gives us the opportunity to study such complex mechanisms in relatively simple organisms in which both genetic and biochemical approaches can be easily used.
MULTIMODAL REPRESENTATION OF SPACE IN THE POSTERIOR PARIETAL CORTEX AND ITS USE IN PLANNING MOVEMENTS
Authors: Andersen Richard A. , Snyder Lawrence H. , Bradley David C. , Xing Jing
Published: July 2002

▪ Abstract  Recent experiments are reviewed that indicate that sensory signals from many modalities, as well as efference copy signals from motor structures, converge in the posterior parietal cortex in order to code the spatial locations of goals for movement. These signals are combined using a specific gain mechanism that enables the different coordinate frames of the various input signals to be combined into common, distributed spatial representations. These distributed representations can be used to convert the sensory locations of stimuli into the appropriate motor coordinates required for making directed movements. Within these spatial representations of the posterior parietal cortex are neural activities related to higher cognitive functions, including attention. We review recent studies showing that the encoding of intentions to make movements is also among the cognitive functions of this area.
FUNCTIONAL AND STRUCTURAL COMPLEXITY OF SIGNAL TRANSDUCTION VIA G-PROTEIN-COUPLED RECEPTORS
Authors: Gudermann Thomas , Schöneberg Torsten , Schultz Günter
Published: July 2002

▪ Abstract  A prerequisite for the maintenance of homeostasis in a living organism is fine-tuned communication between different cells. The majority of extracellular signaling molecules, such as hormones and neurotransmitters, interact with a three-protein transmembrane signaling system consisting of a receptor, a G protein, and an effector. These single components interact sequentially and reversibly. Considering that hundreds of G-protein-coupled receptors interact with a limited repertoire of G proteins, the question of coupling specificity is worth considering. G-protein-mediated signal transduction is a complex signaling network with diverging and converging transduction steps at each coupling interface. The recent realization that classical signaling pathways are intimately intertwined with growth-factor–signaling cascades adds another level of complexity. Elaborate studies have significantly enhanced our knowledge of the functional anatomy of G-protein-coupled receptors, and the concept has emerged that receptor function can be modulated with high specificity by coexpressed receptor fragments. These results may have significant clinical impact in the future.
Neural Representation and the Cortical Code
Authors: deCharms R. Christopher , Zador Anthony
Published: July 2002

The principle function of the central nervous system is to represent and transform information and thereby mediate appropriate decisions and behaviors. The cerebral cortex is one of the primary seats of the internal representations maintained and used in perception, memory, decision making, motor control, and subjective experience, but the basic coding scheme by which this information is carried and transformed by neurons is not yet fully understood. This article defines and reviews how information is represented in the firing rates and temporal patterns of populations of cortical neurons, with a particular emphasis on how this information mediates behavior and experience.
Dietary Fat and Breast Cancer
Authors: Lee Marion M. , Lin Scarlett S.
Published: July 2002

One of the most often studied associations in epidemiology is dietary fat and breast cancer risk. That migrants from low-risk countries increase their risk on immigrating to higher-risk countries suggests that some modifiable lifestyle or environmental factor is responsible for the development of breast cancer. Although early international correlational studies and experimental animals studies support dietary fat as a risk factor for breast cancer, more recent data from case-control studies and cohort studies have been equivocal, thus the analytical data do not support a strong positive association. The conflicting results from analytic studies may be due to methodologic issues associated with study design, dietary assessment tools, measurement error, improper statistical analyses, and a lack of heterogeneity in fat intake among the study population. Moreover, current dietary questionnaires may be inadequate in capturing true dietary intakes or capturing the risk with exposure during earlier periods of a woman's life. Although two large clinical trials investigating the fat/breast cancer relationships issue are underway, researchers are generally skeptical at their ability to detect an independent association between fat and breast cancer risk. Further epidemiologic studies using current methodology may not prove to be fruitful in generating definitive answers to shed light on this controversial issue. In addition, rather than concentrating on dietary fat, researchers should focus on diets that are not only low in saturated fat, but also high in fruit and vegetable consumption. Researchers should take advantage of advances in molecular and genetic technology for a different perspective in examining the issue. For example, markers of susceptibility to breast cancer that can detect women at higher risk for breast cancer may be helpful in clarifying the role of dietary fat. More comprehensive and multiple approaches to studying dietary factors and breast cancer are recommended.
DIETARY FLAVONOIDS: Bioavailability, Metabolic Effects, and Safety
Authors: Ross Julie A. , Kasum Christine M.
Published: July 2002

▪ Abstract  Flavonoids comprise the most common group of plant polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5000 different flavonoids have been described. The six major subclasses of flavonoids include the flavones (e.g., apigenin, luteolin), flavonols (e.g., quercetin, myricetin), flavanones (e.g., naringenin, hesperidin), catechins or flavanols (e.g., epicatechin, gallocatechin), anthocyanidins (e.g., cyanidin, pelargonidin), and isoflavones (e.g., genistein, daidzein). Most of the flavonoids present in plants are attached to sugars (glycosides), although occasionally they are found as aglycones. Interest in the possible health benefits of flavonoids has increased owing to their potent antioxidant and free-radical scavenging activities observed in vitro. There is growing evidence from human feeding studies that the absorption and bioavailability of specific flavonoids is much higher than originally believed. However, epidemiologic studies exploring the role of flavonoids in human health have been inconclusive. Some studies support a protective effect of flavonoid consumption in cardiovascular disease and cancer, other studies demonstrate no effect, and a few studies suggest potential harm. Because there are many biological activities attributed to the flavonoids, some of which could be beneficial or detrimental depending on specific circumstances, further studies in both the laboratory and with populations are warranted.
Neurokinin1 Receptor Antagonists as Potential Antidepressants
Authors: Stout Steven C. , Owens Michael J. , Nemeroff Charles B.
Published: July 2002

Selective, nonpeptide antagonists for tachykinin receptors first became available ten years ago. Of the three known tachykinin receptors, drug development has focused most intensively on the substance P-preferring receptor, neurokinin1 (NK1). Although originally studied as potential analgesic compounds, recent evidence suggests that NK1 receptor antagonists may possess antidepressant and anxiolytic properties. If confirmed by further controlled clinical studies, this will represent a mechanism of action distinct from all existing antidepressant agents. As reviewed in this chapter, the existing preclinical and clinical literature is suggestive of, but not conclusive, concerning a role of substance P and NK1 receptors in the pathophysiology of depression and/or anxiety disorders. The ongoing clinical trials with NK1 receptor antagonists have served as an impetus for much needed, basic research in this field.
Self-Assembled Ceramics Produced by Complex-Fluid Templation
Authors: Dabbs Daniel M. , Aksay Ilhan A.
Published: July 2002

This review examines the use of self-assembly in the fabrication of ceramic mesostructures, emphasizing the use of amphiphilic surfactants and block copolymers. The association between this area of research and biomimetics is discussed, linking developments in synthetic self-assembly with biomineralization. The fabrication of hierarchical structures through the use of simultaneous processing is shown to be a necessary condition for applications of this new technology.
PULSEDEPR SPECTROSCOPY: Biological Applications
Authors: Prisner Thomas , Rohrer Martin , MacMillan Fraser
Published: July 2002

▪ Abstract  Pulsed electron paramagnetic resonance (EPR) methods such as ESEEM, PELDOR, relaxation time measurements, transient EPR, high-field/high-frequency EPR, and pulsed ENDOR, have been used successfully to investigate the local structure and dynamics of paramagnetic centers in biological samples. These methods allow different contributions to the EPR spectra to be distinguished and can help unravel complicated EPR spectra consisting of overlapping resonance lines, as are often found in disordered protein samples. The basic principles, specific potentials, technical requirements, and limitations of these advanced EPR techniques will be reviewed together with recent applications to metal centers, organic radicals, and spin labels in proteins.
SPIN-1/2 AND BEYOND: A Perspective in Solid State NMR Spectroscopy
Authors: Frydman Lucio
Published: July 2002

▪ Abstract  Novel applications of solid state nuclear magnetic resonance (NMR) to the study of small molecules, synthetic polymers, biological systems, and inorganic materials continue at an accelerated rate. Instrumental to this uninterrupted expansion has been an improved understanding of the chemical physics underlying NMR. Such deeper understanding has led to novel forms of controlling the various components that make up the spin interactions, which have in turn redefined the analytical capabilities of solid state NMR measurements. This review presents a perspective on the basic phenomena and manipulations that have made this progress possible and describes the new opportunities and challenges that are being opened in the realms of spin-1/2 and quadrupole nuclei spectroscopies.
PULLING THE CART AND ENJOYING THE RIDE
Authors: Hunt Carlton C.
Published: July 2002

▪ Abstract  I was pleased to receive the invitation to write this prefatory chapter. In doing so, I join a number of physiologists whose work and writings I have often admired. There are two aspects of my experience in physiology that I discuss here. The first concerns my own research accomplishments. The second is my role in developing three departments of physiology and fostering the careers of others. While I take pleasure in the former, the overall contribution of the latter was undoubtedly greater.
ELECTROPHYSIOLOGY OF SYNAPTIC VESICLE CYCLING
Authors: von Gersdorff Henrique , Matthews Gary
Published: July 2002

▪ Abstract  Patch-clamp capacitance measurements can monitor in real time the kinetics of exocytosis and endocytosis in living cells. We review the application of this technique to the giant presynaptic terminals of goldfish bipolar cells. These terminals secrete glutamate via the fusion of small, clear-core vesicles at specialized, active zones of release called synaptic ribbons. We compare the functional characteristics of transmitter release at ribbon-type and conventional synapses, both of which have a unique capacity for fast and focal vesicle fusion. Subsequent rapid retrieval and recycling of fused synaptic vesicle membrane allow presynaptic terminals to function independently of the cell soma and, thus, as autonomous computational units. Together with the mobilization of reserve vesicle pools, local cycling of synaptic vesicles may delay the onset of vesicle pool depletion and sustain neuronal output during high stimulation frequencies.
Spatial Considerations for Stimulus-Dependent Transcription in Neurons
Authors: Ahn Sohyun , Riccio Antonella , Ginty David D.
Published: July 2002

▪ Abstract  Most neurons have elaborate dendrites as well as an axon emanating from the cell body that form synaptic connections with one or many target cells, which may be located a considerable distance from the cell body. Such complex and impressive morphologies allow some types of neurons to integrate inputs from one to many thousands of pre-synaptic partners and to rapidly propagate electrical signals, often over long distances, to post-synaptic target cells. Much slower, non-electrical signals also propagate from dendrites and distal axons to neuronal nuclei that influence survival, growth, and plasticity. The distances between distal dendrites and/or distal axons and cell bodies of neurons can be hundreds of microns to more than one meter. This long-range biochemical signal propagation from distal dendrites and distal axons to neuronal nuclei is entirely unique to neurons. This review is focused on excitatory neurotransmitter signaling from dendritic synapses to neuronal nuclei as well as on retrograde growth factor signaling from distal axons to neuronal nuclei.