bluuebunny/crossref_metadata_2025 huggingface dataset:
Specification and verification of pipelining in the ARM2 RISC microprocessor
Authors: Huggins James K. , Campenhout David Van
Published: July 2002

Gurevich Abstract State Machines (ASMs) provide a sound mathematical basis for the specification and verification of systems. An application of the ASM methodology to the verification of a pipelined microprocessor (an ARM2 implementation) is described. Both the sequential execution model and final pipelined model are formalized using ASMs. A series of intermediate models are introduced that gradually expose the complications of pipelining. The first intermediate model is proven equivalent to the sequential model in the absence of structural, control, and data hazards. In the following steps, these simplifying assumptions are lifted one by one, and the original proof is refined to establish the equivalence of each intermediate model with the sequential model, leading ultimately to a full proof of equivalence of the sequential and pipelined models.
Two-level logic minimization for low power
Authors: Tseng Jyh-Mou , Jou Jing-Yang
Published: July 2002

In this paper we present a complete Boolean method for reducing the power consumption in two-level combinational circuits. The two-level logic optimizer performs the logic minimization for low power targeting static PLA, general logic gates, and dynamic PLA implementations. We modify the espresso algorithm by adding our heuristics, which bias logic minimization toward lowering power dissipation. In our heuristics, signal probabilities and transition densities are two important parameters. The experimental results are promising.
Algorithm 791: TSHEP2D
Authors: Renka Robert J. , Brown Ron
Published: July 2002

We describe a new algorithm for scattered data interpolation. It is based on a modified Shepard method similar to that of Algorithm 660 but uses 10-parameter cosine series nodal functions in place of quadratic polynomials. Also, the interpolant has continuous second partial derivatives. An accompanying survey article presents test results that show the method to be more accurate than polynomial-based methods in terms of reproducing test functions with large variations and steep gradients.
The Independence of Inherent Ambiguity From Complementedness Among Context-Free Languages
Authors: Hibbard Thomas N. , Ullian Joseph
Published: July 2002

Call a (context-free) language unambiguous if it is not inherently ambiguous. In the absence of evidence to the contrary, the suspicion has arisen that the unambiguous languages might be precisely those languages with context-free complements. The two theorems presented in this paper lay the suspicion to rest by providing (1) an inherently ambiguous language with context-free complement and (2) an unambiguous language without context-free complement. This establishes the independence of inherent ambiguity from complementedness among the context-free languages.
On the Compatibility of a Given Solution With the Data of a Linear System
Authors: Rigal J. L. , Gaches J.
Published: July 2002

Some new theorems generalizing a result of Oettli and Prager are applied to the a posteriori analysis of the
compatibility
of a computed solution to the uncertain data of a linear system (or of a polynomial equation).
A Formal Deductive Problem-Solving System
Authors: Quinlan J. R. , Hunt E. B.
Published: July 2002

A formalism is defined in which solutions to theorem-proving and similar problems take the form of a sequence of transformations of states into other states. The data used to solve a problem then consists of a set of rewriting rules which defines the allowable transformations. A method for selecting “useful” transformations, i.e. those which will most probably lead to a solution, is developed.

Two problem-solving processes based on the above are defined; one, called the FORTRAN Deductive System (FDS) is shown to be more powerful than the other. A class of problems to which FDS will always find solutions is constructed. Examples of solutions found by a computer implementation of FDS are given and, in some cases, are compared with human performance.

Finally, FDS is compared with some of the better-known problem-solving systems.
Linear Multistep Methods for Volterra Integro-Differential Equations
Authors: Linz Peter
Published: July 2002

The Dahlquist stability analysis for ordinary differential equations is extended to the case of Volterra integro-differential equations. Thus the standard multistep methods can be generalized to furnish algorithms for solving integro-differential equations. Special starting procedures are discussed, and some numerical examples are presented.
A New Method of Interpolation and Smooth Curve Fitting Based on Local Procedures
Authors: Akima Hiroshi
Published: July 2002

A new mathematical method is developed for interpolation from a given set of data points in a plane and for fitting a smooth curve to the points. This method is devised in such a way that the resultant curve will pass through the given points and will appear smooth and natural. It is based on a piecewise function composed of a set of polynomials, each of degree three, at most, and applicable to successive intervals of the given points. In this method, the slope of the curve is determined at each given point locally, and each polynomial representing a portion of the curve between a pair of given points is determined by the coordinates of and the slopes at the points. Comparison indicates that the curve obtained by this new method is closer to a manually drawn curve than those drawn by other mathematical methods.
Scheduling Algorithms for Multiprogramming in a Hard-Real-Time Environment
Authors: Liu C. L. , Layland James W.
Published: July 2002

The problem of multiprogram scheduling on a single processor is studied from the viewpoint of the characteristics peculiar to the program functions that need guaranteed service. It is shown that an optimum fixed priority scheduler possesses an upper bound to processor utilization which may be as low as 70 percent for large task sets. It is also shown that full processor utilization can be achieved by dynamically assigning priorities on the basis of their current deadlines. A combination of these two scheduling techniques is also discussed.
A Code for the Transportation Problem of Linear Programming
Authors: Harris Britton
Published: July 2002

Methods are described and results presented for greatly reducing the computation time for long narrow problems of the transportation problem of linear programming. The code builds on known methods with two principal innovations: a substantial reduction in the size of the tree representation of shipments, and a set of methods for calculating improved starting solutions.
A plausibility-driven approach to computer architecture design
Authors: Agüero Ulises , Sasgupta Subrata
Published: July 2002

A dilemma skirting the discipline of computer architecture concerns the plausibility of architectural designs. To counter the widely held perception that architecture is a nebulous entity is a proposal to view such designs as specifications of constraints to be satisfied.
Integration of synchronous and asynchronous collaboration activities
Authors: Jackson Larry S. , Grossman Ed
Published: July 2002

The inegrated synchronous and asynchronous collaboration (ISAAC) project [1] is constructing a communication and collaboration system to bridge traditional workgroup barriers of time and space. Possible applications include military command and control, corporate real-time collaboration, and distributed teams of research scientists. Thus, this system must host the widest possible range of applications, and must run on heterogeneous hardware.

ISAAC incorporates real-time (synchronous) collaboration technologies developed by the Habanero® project [2,3] at the National Center for Supercomputing Applications at the
University of Illinois Urbana-Champaign, with asynchronous extensions. ISAAC research is aimed at moving information between synchronous and asynchronous modes. ISAAC's session capture conceptually transforms a real-time multiple tool collaboration into multimedia document, which can be analyzed and reused by other programs. Automated segmentation and indexing of captured audio and videoteleconference traffic adds further information.
Symbolic synthesis of clock-gating logic for power optimization of synchronous controllers
Authors: Benini L. , De Micheli G. , Macii E. , Poncino M. , Scarsi R.
Published: July 2002

Recent results have shown that dynamic power management is effective in reducing the total power consumption of sequential circuits. In this paper, we propose a bottom-up approach for the automatic extraction and synthesis of dynamic power management circuitry starting from structural logic-level specifications. Our techniques leverage the compact BDD-based representation of Boolean and pseudo-Boolean functions to detect idle conditions where the clock can be stopped without compromising functional correctness. Moreover, symbolic techniques allow accurate probabilistic computations; in particular, they enable the use of non-equiprobable primary input distributions, a key step in the construction of models that match the behavior of real hardware devices with a high degree of fidelity. The results are encouraging, since power savings of up to 34% have been obtained on standard benchmark circuits.
Structural gate decomposition for depth-optimal technology mapping in LUT-based FPGA designs
Authors: Cong Jason , Hwang Yean-Yow
Published: July 2002

In this paper we study structural gate decomposition in general, simple gate networks for depth-optimal technology mapping using
K
-input Lookup-Tables (
K
-LUTs). We show that (1) structural gate decomposition in any
K
-bounded network results in an optimal mapping depth smaller than or equal to that of the original network, regardless of the decomposition method used; and (2) the problem of structural gate decomposition for depth-optimal technology mapping is NP-hard for
K
-unbounded networks when
K
≥3 and remains NP-hard for
K
-boundeds networks when
K
≥5. Based on these results, we propose two new structural gate decomposition algorithms, named DOGMA and DOGMA-m, which combine the level-driven node-packing technique (used in FlowMap) and the network flow-based labeling technique (used in Chortle-d) for depth-optimal technology mapping. Experimental results show that (1) among five structural gate decompostion algorithms, DOGMA-m results in the best mapping solutions; and (2) compared with speed_up(an algebraic algorithm) and TOS (a Boolean approach), DOGMA-m completes, decomposition of all tested benchmarks in a short time while speed_up and TOS fail in several cases. However, speed_up results in the smallest depth and area in the following technology mapping steps.
Using the visual differences predictor to improve performance of progressive global illumination computation
Authors: Volevich Valdimir , Myszkowski Karol , Khodulev Andrei , Kopylov Edward A.
Published: July 2002

A novel view-independent technique for progressive global illumination computing that uses prediction of visible differences to improve both efficiency and effectiveness of physically-sound lighting solutions has been developed. The technique is a mixture of stochastic (density estimation) and deterministic (adaptive mesh refinement) algorithms used in a sequence and optimized to reduce the differences between the intermediate and final images as perceived by the human observer in the course of lighting computation. The quantitive measurements of visibility were obtained using the model of human vision captured in the visible differences predictor (VDP) developed by Daly [1993]. The VDP responses were used to support the selection of the best component algorithms from a pool of global illumination solutions, and to enhance the selected algorithms for even better progressive refinement of image quality. The VDP was also used to determine the optimal sequential order of component-algorithm execution, and to choose the points at which switchover between algorithms should take place. As the VDP is computationally expensive, it was applied exclusively at the design and tuning stage of the composite technique, and so perceptual considerations are embedded into the resulting solution, though no VDP calculations were performed during lighting simulation.

The proposed illumination technique is also novel, providing intermediate image solutions of high quality at unprecedented speeds, even for complex scenes. One advantage of the technique is that local estimates of global illumination are readily available at the early stages of computing, making possible the development of a more robust adaptive mesh subdivision, which is guided by local contrast information. Efficient object space filtering, also based on stochastically-derived estimates of the local illumination error, is applied to substantially reduce the visible noise inherent in stochastic solutions.
A generic model for reflective design
Authors: Louridas Panagiotis , Loucopoulos Pericles
Published: July 2002

Rapid technological change has had an impact on the nature of software. This has led to new exigencies and to demands for software engineering paradigms that pay particular atttention to meeting them. We advocate that such demands can be met, at least in large parts, through the adoption of software engineering processes that are founded on a reflective stance. To this end, we turn our attention to the field of Design Rationale. We analyze and characterize Design Rationale approaches and show that despite surface differences between different approaches, they all tend to be variants of a relatively small set of static and dynamic affinities. We use the synthesis of static and dynamic affinities to develop a generic model for reflective design. The model is nonprescriptive and affects minimally the design process. It is context-independent and is intended to be used as a facilitator in participative design, supporting group communication and deliberation. The potential utility of the model is demonstrated through two examples, one from the world of business design and the other from programming language design
Reflections on trusting trust
Authors: Thompson Ken
Published: July 2002

To what extent should one trust a statement that a program is free of Trojan horses? Perhaps it is more important to trust the people who wrote the software.
Implications of structured programming for machine architecture
Authors: Tanenbaum Andrew S.
Published: July 2002

Based on an empirical study of more than 10,000 lines of program text written in a GOTO-less language, a machine architecture specifically designed for structured programs is proposed. Since assignment, CALL, RETURN, and IF statements together account for 93 percent of all executable statements, special care is given to ensure that these statements can be implemented efficiently. A highly compact instruction encoding scheme is presented, which can reduce program size by a factor of 3. Unlike a Huffman code, which utilizes variable length fields, this method uses only fixed length (1-byte) opcode and address fields. The most frequent instructions consist of a single 1-byte field. As a consequence, instruction decoding time is minimized, and the machine is efficient with respect to both space and time.
A comparison of simulation event list algorithms
Authors: Vaucher Jean G. , Duval Pierre
Published: July 2002

Four algorithms are considered which can be used to schedule events in a general purpose discrete simulation system. Two of the algorithms are new, one is based on an end-order tree structure for event notices, and another uses an indexed linear list. The algorithms are tested with a set of typical stochastic scheduling distributions especially chosen to show the advantages and limitations of the algorithms. The end-order tree algorithm is shown to be an advantageous, immediate replacement for the algorithm in use with current simulation languages. The most promising algorithm uses the indexed list concept. It will require an adaptive routine before it can be employed in general purpose simulators, but its performance is such that further study would be fruitful.
A computer system for transformational grammar
Authors: Friedman Joyce
Published: July 2002

A comprehensive system for transformational grammar has been designed and implemented on the IBM 360/67 computer. The system deals with the transformational model of syntax, along the lines of Chomsky's
Aspects of the Theory of Syntax
. The major innovations include a full, formal description of the syntax of a transformational grammar, a directed random phrase structure generator, a lexical insertion algorithm, an extended definition of analysis, and a simple problem-oriented programming language in which the algorithm for application of transformations can be expressed. In this paper we present the system as a whole, first discussing the general attitudes underlying the development of the system, then outlining the system and discussing its more important special features. References are given to papers which consider some particular aspect of the system in detail.
Programming Techniques: Regular expression search algorithm
Authors: Thompson Ken
Published: July 2002

A method for locating specific character strings embedded in character text is described and an implementation of this method in the form of a compiler is discussed. The compiler accepts a regular expression as source language and produces an IBM 7094 program as object language. The object program then accepts the text to be searched as input and produces a signal every time an embedded string in the text matches the given regular expression. Examples, problems, and solutions are also presented.
Processor verification using efficient reductions of the logic of uninterpreted functions to propositional logic
Authors: Bryant Randal E. , German Steven , Velev Miroslav N.
Published: July 2002

The logic of Equality with Uninterpreted Functions (EUF) provides a means of abstracting the manipulation of data by a processor when verifying the correctness of its control logic. By reducing formulas in this logic to propositional formulas, we can apply Boolean methods such as ordered Binary Decision Diagrams (BDDs) and Boolean satisfiability checkers to perform the verification. We can exploit characteristics of the formulas describing the verification conditions to greatly simplfy the propostional formulas generated. We identify a class of terms we call “p-terms” for which equality comparisons can only be used in monotonically positive formulas. By applying suitable abstractions to the hardware model, we can express the functionality of data values and instruction addresses flowing through an instruction pipeline with p-terms. A decision procedure can exploit the restricted uses of p-terms by considering only “maximally diverse” interpretations of the associated function symbols, where every function application yields a different value execept when constrainted by functional consistency. We present two methods to translate formulas in EUF into propositional logic. The first interprets the formula over a domain of fixed-length bit vectors and uses vectors of propositional variables to encode domain variables. The second generates formulas encoding the conditions under which pairs of terms have equal valuations, introducing propostional variables to encode the equality relations between pairs of terms. Both of these approaches can exploit maximal diversity to greatly reduce the number of propositional variables that need to be introduced and to reduce the overall formula sizes. We present experimental results demonstrating the efficiency of this approach when verifying pipelined processors using the method proposed by Burch and Dill. Exploiting positive equality allows us to overcome the experimental blow-up experienced previously when verifying microprocessors with load, store, and branch instructions.
Algorithm 810: The SLEIGN2 Sturm-Liouville Code
Authors: Bailey P. B. , Everitt W. N. , Zettl A.
Published: July 2002

The SLEIGN2 code is based on the ideas and methods of the original SLEIGN code of 1979. The main purpose of the SLEIGN2 code is to compute eigenvalues and eigenfunctions of regular and singular self-adjoint Sturm-Liouville problems, with both separated and coupled boundary conditions, and to approximate the continuous spectrum in the singular case. The code uses some new algorithms, which we describe, and has a driver program that offers a user-friendly interface. In this paper the algorithms and their implementations are discussed, and the class of problems to which each algorithm applied is identified.
Rule-based systems
Authors: Hayes-Roth Frederick
Published: July 2002

Rule-based systems automate problem-solving know-how, provide a means for capturing and refining human expertise, and are proving to be commercially viable.
An optimal strategy for sellers in an online auction
Authors: Guo Xin
Published: July 2002

We consider an online auction setting where the seller attempts to sell an item. Bids arrive over time and the seller has to make an instant decision to either accept this bid and close the auction or reject it and move on to the next bid, with the hope of higher gains. What should be the seller's strategy to maximize gains? Using techniques from convex analysis, we provide an explicit closed-form optimal solution (and hence a simple optimum online algorithm) for the seller.Our methodology is attractive to online auction systems that have to make an instant decision, especially when it is not humanly possible to evaluate each bid individually, when the number of bids is large or unknown ahead of time, and when the bidders are unwilling to wait.
Prefetching for improved bus wrapper performance in cores
Authors: Lysecky Roman , Vahid Frank
Published: July 2002

Reuse of cores can reduce design time for systems-on-a-chip. Such reuse is dependent on being able to easily interface a core to any bus. To enable such interfacing, many propose separating a core's interface from its internals by using a bus wrapper. However, this separation can lead to a performance penalty when reading a core's internal registers. In this paper, we introduce prefetching, which is analogous to caching, as a technique to reduce or eliminate this performance penalty, involving a tradeoff with power and size. We describe the prefetching technique, classify different types of registers, describe our initial prefetching architectures and heuristics for certain classes of registers, and highlight experiments demonstrating the performance improvements and size/power tradeoffs. We further introduce a technique for automatically designing a prefetch unit that satisfies user-imposed register-access constraints. The technique benefits from mapping the prefetching problem to the well-known real-time process scheduling problem. We then extend the technique to allow user-specified register interdependencies, using a Petri net model, resulting in even more efficient prefetch schedules.
Satisfiability models and algorithms for circuit delay computation
Authors: Guerra e Silva Luís , Marques-Silva João , Silveira L. Miguel , Sakallah Karem A.
Published: July 2002

The existence of false paths represents a significant and computationally complex problem in the estimation of the true delay of combinational and sequential circuits. In this article we conduct a comprehensive study of modeling circuit delay computation, accounting for false paths, as a sequence of instances of Boolean satisfiability. Several path sensitization models and delay models are studied. In addition we evaluate some of the most competitive Boolean satisfiability algorithms seeking to identify which are best suited for solving circuit delay computation problems. Finally, realistic delay modeling (taking into account extracted interconnect delays and fanout data) is considered in order to experimentally evaluate the complexity of solving real-world instances.
The application of scene synthesis techniques to the display of multidimensional image data
Authors: Robertson Philip K. , O'Callaghan John F.
Published: July 2002

Superimposition of two image data sets allows the spatial distribution of one to be directly related to that of the other. If the two data sets have different spatial structures, the composite image is generally confusing and difficult to interpret. A method of representing image data sets in the form of naturally occurring variables in a realistic apparently three-dimensional scene is presented. One data set is represented by the topography of a surface, depicted by shaded-relief methods, while another is represented by the color of the surface, or by the color of an overlaid transparency. Presentation in this form exploits the normal scene decomposition abilities of the human visual system, allowing intuitive appreciation and separation of the scene, and hence data set, variables. The method relies on techniques for the modeling of surfaces and surface reflectance to render the synthesised scenes realistically.
Comments on "Grosch's law re-revisited: CPU power and the cost of computation"
Authors: Kang Young Moo , Miller Robert B. , Pick Roger Alan
Published: July 2002

Taking Ein-Dor's recent reevaluation of Grosch's law one step further, the authors find evidence of different slopes for different classes of computers and the utility of an additional variable: the IBM or IBM-compatible factor. The analysis indicates that Grosch's law no longer applies to minicomputers.
Approximating grammar probabilities
Authors: Chaudhuri R. , Rao A. N. V.
Published: July 2002

It is proved that the production probabilities of a probabilistic context-free grammar may be obtained as the limit of the estimates inferred from an increasing sequence of randomly drawn samples from the language generated by the grammar.
Adapting UNIX for a multiprocessor environment
Authors: Janssens M. D , Annot J. K , Van De Goor A. J
Published: July 2002

Existing Unix data protection and synchronization mechanisms present difficulties when adapting Unix to a multiprocessor environment, but solutions do exist.
Applications of combinatorial designs in computer science
Authors: Colbourn Charles J. , van Oorschot Paul C.
Published: July 2002

The theory of combinatorial designs has been used in widely different areas of computation concerned with the design and analysis of both algorithms and hardware. Combinatorial designs capture a subtle balancing property that is inherent in many difficult problems and hence can provide a sophisticated tool for addressing these problems. The role of combinatorial designs in solving many problems that are basic to the field of computing is explored in this paper. Case studies of many applications of designs to computation are given; these constitute a first survey, which provides a representative sample of uses of designs. More importantly, they suggest paradigms in which designs can be used profitably in algorithm design and analysis.
An evaluation tool for measuring authoring system performance
Authors: MacKnight Carol B. , Balagopalan Santosh
Published: July 2002

A model for producing objective and precise measurements of the power and performance of authoring systems is described. An animation task is given as an example of the model's potential as a tool for evaluating authoring systems along the dimensions of functionality, flexibility, and productivity.
Algorithm 685: a program for solving separable elliptic equations
Authors: Kaufman Linda , Warner Daniel D.
Published: July 2002

This paper persents a program SERRG2 that solves separable elliptic equations on a rectangle. The program uses a matrix decomposition technique to directly solve the linear system arising from a Rayleigh-Ritz-Galerkin approach with tensor product B-splines to solve the separable partial differential equation. This approach permits high-order discretizations, variable meshes, and multiple knots.
DWARF GALAXIES OF THE LOCAL GROUP
Authors: Mateo Mario
Published: July 2002

▪ Abstract  The Local Group dwarf galaxies offer a unique window to the detailed properties of the most common type of galaxy in the Universe. In this review, I update the census of Local Group dwarfs based on the most recent distance and radial velocity determinations. I then discuss the detailed properties of this sample, including (a) the integrated photometric parameters and optical structures of these galaxies, (b) the content, nature, and distribution of their interstellar medium (ISM), (c) their heavy-element abundances derived from both stars and nebulae, (d) the complex and varied star-formation histories of these dwarfs, (e) their internal kinematics, stressing the relevance of these galaxies to the “dark matter problem” and to alternative interpretations, and (f) evidence for past, ongoing, and future interactions of these dwarfs with other galaxies in the Local Group and beyond. To complement the discussion and to serve as a foundation for future work, I present an extensive set of basic observational data in tables that summarize much of what we know and do not know about these nearby dwarfs. Our understanding of these galaxies has grown impressively in the past decade, but fundamental puzzles remain that will keep the Local Group at the forefront of galaxy evolution studies for some time.
Membrane Fusion and Exocytosis
Authors: Jahn Reinhard , Südhof Thomas C.
Published: July 2002

▪ Abstract  Membrane fusion involves the merger of two phospholipid bilayers in an aqueous environment. In artificial lipid bilayers, fusion proceeds by means of defined transition states, including hourglass-shaped intermediates in which the proximal leaflets of the fusing membranes are merged whereas the distal leaflets are separate (fusion stalk), followed by the reversible opening of small aqueous fusion pores. Fusion of biological membranes requires the action of specific fusion proteins. Best understood are the viral fusion proteins that are responsible for merging the viral with the host cell membrane during infection. These proteins undergo spontaneous and dramatic conformational changes upon activation. In the case of the paradigmatic fusion proteins of the influenza virus and of the human immunodeficiency virus, an amphiphilic fusion peptide is inserted into the target membrane. The protein then reorients itself, thus forcing the fusing membranes together and inducing lipid mixing. Fusion of intracellular membranes in eukaryotic cells involves several protein families including SNAREs, Rab proteins, and Sec1/Munc-18 related proteins (SM-proteins). SNAREs form a novel superfamily of small and mostly membrane-anchored proteins that share a common motif of about 60 amino acids (SNARE motif). SNAREs reversibly assemble into tightly packed helical bundles, the core complexes. Assembly is thought to pull the fusing membranes closely together, thus inducing fusion. SM-proteins comprise a family of soluble proteins that bind to certain types of SNAREs and prevent the formation of core complexes. Rab proteins are GTPases that undergo highly regulated GTP-GDP cycles. In their GTP form, they interact with specific proteins, the effector proteins. Recent evidence suggests that Rab proteins function in the initial membrane contact connecting the fusing membranes but are not involved in the fusion reaction itself.
AKT/PKB and Other D3 Phosphoinositide-Regulated Kinases: Kinase Activation by Phosphoinositide-Dependent Phosphorylation
Authors: Chan Tung O. , Rittenhouse Susan E. , Tsichlis Philip N.
Published: July 2002

▪ Abstract  The protein kinase Akt/PKB is activated via a multistep process by a variety of signals. In the early steps of this process, PI-3 kinase-generated D3-phosphorylated phosphoinositides bind the Akt PH domain and induce the translocation of the kinase to the plasma membrane where it co-localizes with phosphoinositide-dependent kinase-1. By binding to the PH domains of both Akt and phosphoinositide-dependent kinase-1, D3-phosphorylated phosphoinositides appear to also induce conformational changes that permit phosphoinositide-dependent kinase-1 to phosphorylate the activation loop of Akt. The paradigm of Akt activation via phosphoinositide-dependent phosphorylation provided a framework for research into the mechanism of activation of other members of the AGC kinase group (p70S6K, PKC, and PKA) and members of the Tec tyrosine kinase family (TecI, TecII, Btk/Atk, Itk/Tsk/Emt, Txk/Rlk, and Bm/Etk). The result was the discovery that these kinases and Akt are activated by overlapping pathways. In this review, we present our current understanding of the regulation and function of the Akt kinase and we discuss the common and unique features of the activation processes of Akt and the AGC and Tec kinase families. In addition, we present an overview of the biosynthesis of phosphoinositides that contribute to the regulation of these kinases.
DNA Replication Fidelity
Authors: Kunkel Thomas A. , Bebenek Katarzyna
Published: July 2002

▪ Abstract  DNA replication fidelity is a key determinant of genome stability and is central to the evolution of species and to the origins of human diseases. Here we review our current understanding of replication fidelity, with emphasis on structural and biochemical studies of DNA polymerases that provide new insights into the importance of hydrogen bonding, base pair geometry, and substrate-induced conformational changes to fidelity. These studies also reveal polymerase interactions with the DNA minor groove at and upstream of the active site that influence nucleotide selectivity, the efficiency of exonucleolytic proofreading, and the rate of forming errors via strand misalignments. We highlight common features that are relevant to the fidelity of any DNA synthesis reaction, and consider why fidelity varies depending on the enzymes, the error, and the local sequence environment.
How Matrix Metalloproteinases Regulate Cell Behavior
Authors: Sternlicht Mark D. , Werb Zena
Published: July 2002

▪ Abstract  The matrix metalloproteinases (MMPs) constitute a multigene family of over 25 secreted and cell surface enzymes that process or degrade numerous pericellular substrates. Their targets include other proteinases, proteinase inhibitors, clotting factors, chemotactic molecules, latent growth factors, growth factor–binding proteins, cell surface receptors, cell-cell adhesion molecules, and virtually all structural extracellular matrix proteins. Thus MMPs are able to regulate many biologic processes and are closely regulated themselves. We review recent advances that help to explain how MMPs work, how they are controlled, and how they influence biologic behavior. These advances shed light on how the structure and function of the MMPs are related and on how their transcription, secretion, activation, inhibition, localization, and clearance are controlled. MMPs participate in numerous normal and abnormal processes, and there are new insights into the key substrates and mechanisms responsible for regulating some of these processes in vivo. Our knowledge in the field of MMP biology is rapidly expanding, yet we still do not fully understand how these enzymes regulate most processes of development, homeostasis, and disease.
CHINESE LOESS AND THE PALEOMONSOON
Authors: Liu Tungsheng , Ding Zhongli
Published: July 2002

▪ Abstract  This paper presents a general review of the recent research advances of the East Asian paleomonsoon, based mainly on studies of the loess-soil sequences in the Chinese Loess Plateau. In the last 2.6 million years, the paleomonsoonal history may be divided into about 166 events on a time scale of the Earth's orbital variations. During the last glacial period, millenial-scale oscillations of the monsoon system were prominent, which can be fairly well correlated with the Dansgaard-Oeschger cycles recognized in the Greenland ice cores. The monsoonal rainfall belt has experienced a wide, repeated advance-retreat change during the glacial-interglacial cycles of the Pleistocene. Both temporal and spatial changes of the monsoon system in the Quaternary could have been linked closely to global ice-volume variations.
LABORATORY-DERIVED FRICTION LAWS AND THEIR APPLICATION TO SEISMIC FAULTING
Authors: Marone Chris
Published: July 2002

▪ Abstract  This paper reviews rock friction and the frictional properties of earthquake faults. The basis for rate- and state-dependent friction laws is reviewed. The friction state variable is discussed, including its interpretation as a measure of average asperity contact time and porosity within granular fault gouge. Data are summarized showing that friction evolves even during truly stationary contact, and the connection between modern friction laws and the concept of “static” friction is discussed. Measurements of frictional healing, as evidenced by increasing static friction during quasistationary contact, are reviewed, as are their implications for fault healing. Shear localization in fault gouge is discussed, and the relationship between microstructures and friction is reviewed. These data indicate differences in the behavior of bare rock surfaces as compared to shear within granular fault gouge that can be attributed to dilation within fault gouge. Physical models for the characteristic friction distance are discussed and related to the problem of scaling this parameter to seismic faults. Earthquake afterslip, its relation to laboratory friction data, and the inverse correlation between afterslip and shallow coseismic slip are discussed in the context of a model for afterslip. Recent observations of the absence of afterslip are predicted by the model.
IT'S NOT EASY BEING GREEN: Environmental Technologies Enhance Conventional Hydropower's Role in Sustainable Development
Authors: March Patrick A. , Fisher Richard K.
Published: July 2002

▪ Abstract  Conventional hydroelectric generation uses a renewable energy source and currently supplies ∼10% of the annual output of electricity in the United States and ∼20% of electricity generated worldwide. To provide a significant contribution to sustainable development, the hydropower industry must address a variety of environmental concerns, including water quality and fish passage issues. The paper discusses new technologies for turbine design and control systems to improve dissolved oxygen levels in turbine discharges and survival of fish during turbine passage. The paper describes development, testing, and test results for these technologies, with an emphasis on collaboration of stakeholders and balance between environmental stewardship and economical power production.
MOLECULARORIENTATIONEFFECTS INVISCOELASTICITY
Authors: Suen Jason K.C. , Joo Yong Lak , Armstrong Robert C.
Published: July 2002

▪ Abstract  Recent advances in the computational modeling of molecular conformational and orientational effects in the flow of viscoelastic fluids are described. These advances involve the coupling of molecular models for the underlying microstructure of macromolecules with the macroscopic equations of change. The kinetic theory for polymeric liquids is described along with the most useful micromechanical models for computing the fluid flow of polymeric liquids. Three levels of description are covered for the computation of molecular orientation effects: methods for molecular models for which closed-form, continuum-like evolution equations for average quantities describing molecular conformations can be obtained, hybrid methods that involve coupling direct solution of the Fokker-Planck equation describing the distribution function for molecular orientations with the equations of change, and hybrid methods that couple stochastic simulations of individual molecule trajectories with the macroscopic equations of change. Illustrative results for rheometric flows (flows with homogeneous, fixed kinematics) and complex flows are given.
GENETICS OF ERYTHROPOIESIS: Induced Mutations in Mice and Zebrafish
Authors: Orkin Stuart H. , Zon Leonard I.
Published: July 2002

▪ Abstract  Production of red blood cells (erythropoiesis) in the vertebrate embryo is critical to its survival and subsequent development. As red cells are the first blood cells to appear in embryogenesis, their origin reflects commitment of mesoderm to an hematopoietic fate and provides an avenue by which to examine the development of the hematopoietic system, including the hematopoietic stem cell (HSC). We discuss the genetics of erythropoiesis as studied in two systems: the mouse and zebrafish (Danio rerio). In the mouse, targeted disruption has established several genes as essential at different stages of hematopoiesis or erythroid precursor cell maturation. In the zebrafish, numerous mutants displaying a wide range of phenotypes have been isolated, although the affected genes are unknown. In comparing mouse knockout and zebrafish mutant phenotypes, we propose a pathway for erythropoiesis that emphasizes the apparent similarity of the mutants and the complementary nature of investigation in the two species. We speculate that further genetic studies in mouse and zebrafish will identify the majority of essential genes and define a regulatory network for hematopoiesis in vertebrates.
G. Ledyard Stebbins and the Evolutionary Synthesis
Authors: Smocovitis Vassiliki Betty
Published: July 2002

[Figure: see text]

▪ Abstract  More than any other individual, Stebbins synthesized knowledge from a disparate set of areas that included plant genetics, systematics, and evolution. This work culminated in 1950 with the appearance of his magnum opus, Variation and Evolution in Plants. This book gave plant evolution a coherent framework that was compatible with that emerging from the work of Theodosius Dobzhansky, Ernst Mayr, G. G. Simpson, and Julian Huxley, and others associated with establishing the synthetic theory of evolution. For this work he is regarded as the botanical “architect” of the evolutionary synthesis.
Current Concepts in the Polycystic Ovary Syndrome
Authors: Dunaif Andrea , Thomas Abraham
Published: July 2002

▪ Abstract  Over the past 20 years, it has been clearly documented that the polycystic ovary syndrome (PCOS) has major metabolic sequelae related to insulin resistance and that insulin resistance plays an important role in the pathogenesis of the reproductive disturbances of the disorder. Family studies have indicated a genetic susceptibility to PCOS. Polycystic ovaries and hyperandrogenemia are present in ∼50% of sisters of affected women. Increased androgen secretion and insulin resistance persist in cultured theca cells and skin fibroblasts, respectively, from women with PCOS; this finding suggests that these are intrinsic, presumably genetic, defects. Insulin resistance and elevated low-density lipoprotein (LDL) levels also cluster in the sisters of women with PCOS, consistent with genetic traits. Moreover, the brothers of women with PCOS have insulin resistance and elevated dehydroepiandrosterone sulfate (DHEAS) levels, which supports a genetic basis for these findings. Family-based studies of linkage and association have implicated several genes in the pathogenesis of PCOS. The strongest evidence to date points to a gene in the region of the insulin receptor. Insulin-sensitizing therapy mitigates the reproductive disturbances of PCOS.
Kaposi's Sarcoma–Associated Herpesvirus: A New DNA Tumor Virus
Authors: Boshoff C. , Chang Y.
Published: July 2002

▪ Abstract  Kaposi's sarcoma–associated herpesvirus (KSHV) is a newly identified gammaherpesvirus associated with all clinical forms of Kaposi's sarcoma (KS), body-cavity–based, primary effusion lymphomas (PELs), and a subset of Castleman's disease (CD). Sequence analysis of the KSHV genome demonstrates an extensive array of genes with homology to cellular genes involved in cell cycle regulation, cell proliferation, apoptosis, and immune modulation. Functional studies indicate that these genes may modify the host cell environment, contributing to the pathogenesis of KSHV-associated disorders. Several KSHV genes have been found to cause dysregulated cell proliferation or to interfere with established tumor suppressor pathways. The epidemiologic association of KSHV with malignancies and the coding features of its genome suggest that it is a new DNA tumor virus.
Ammonia-Oxidizing Bacteria: A Model for Molecular Microbial Ecology
Authors: Kowalchuk George A. , Stephen John R.
Published: July 2002

▪ Abstract  The eutrophication of many ecosystems in recent decades has led to an increased interest in the ecology of nitrogen transformation. Chemolitho-autotrophic ammonia-oxidizing bacteria are responsible for the rate-limiting step of nitrification in a wide variety of environments, making them important in the global cycling of nitrogen. These organisms are unique in their ability to use the conversion of ammonia to nitrite as their sole energy source. Because of the importance of this functional group of bacteria, understanding of their ecology and physiology has become a subject of intense research over recent years. The monophyletic nature of these bacteria in terrestrial environments has facilitated molecular biological approaches in studying their ecology, and progress in this field has been rapid. The ammonia-oxidizing bacteria of the β-subclass Proteobacteria have become somewhat of a model system within molecular microbial ecology, and this chapter reviews recent progress in our knowledge of their distribution, diversity, and ecology.
MOLECULAR BIOLOGY OF ODORANT RECEPTORS IN VERTEBRATES
Authors: Mombaerts Peter
Published: July 2002

▪ Abstract  The initial step in olfactory discrimination involves the interaction of odorous ligands with specific receptors on the surface of olfactory sensory neurons. The foundation for a molecular understanding of odor recognition in vertebrates was provided by the identification of a family of genes encoding putative odorant receptors, by Buck & Axel in 1991 . Odorant receptor (OR) genes form the largest gene family in the vertebrate genome. This review summarizes progress over the past seven years. Major new insights are: Olfaction is accomplished in vertebrates by a very large number of receptors; olfactory sensory neurons express a small subset of the OR repertoire; in rat and mouse, axons of neurons expressing the same OR converge onto defined glomeruli in the olfactory bulb.
CHARACTERIZATION OF GLYCOSYLPHOSPHATIDYLINOSITIOL-ANCHORED, SECRETED, AND INTRACELLULAR VERTEBRATE MONO-ADP-RIBOSYLTRANSFERASES
Authors: Okazaki Ian J. , Moss Joel
Published: July 2002

▪ Abstract  Mono-ADP-ribosylation is a posttranslational modification of proteins in which the ADP-ribose moiety of nicotinamide adenine dinucleotide is transferred to an acceptor amino acid. Five mammalian ADP-ribosyltransferases (ART1–ART5) have been cloned and expression is restricted to tissues such as cardiac and skeletal muscle, leukocytes, brain, and testis. ART1 and ART2 are glycosylphosphatidylinositol (GPI)-anchored ectoenzymes. ART5 appears not to be GPI-linked and may be secreted. In skeletal muscle and lymphocytes, ART1 modifies specific members of the integrin family of adhesion molecules, suggesting that ADP-ribosylation affects cell-matrix or cell-cell interactions. In lymphocytes, ADP-ribosylation of surface proteins is associated with changes in p56lcktyrosine kinase-mediated signaling. The catalytic sites of bacterial toxins and vertebrate transferases have conserved structural features, consistent with a common reaction mechanism. ADP-ribosylation can be reversed by ADP-ribosylarginine hydrolases, resulting in the regeneration of free arginine. Thus, an ADP-ribosylation cycle may play a regulatory role in vertebrate tissues.