bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic data layout for distributed-memory machines
Authors: Kennedy Ken , Kremer Ulrich
Published: October 2002

The goal of languages like Fortran D or High Performance Fortran (HPF) is to provide a simple yet efficient machine-independent parallel programming model. After the algorithm selection, the data layout choice is the key intellectual challenge in writing an efficient program in such languages. The performance of a data layout depends on the target compilation system, the target machine, the problem size, and the number of available processors. This makes the choice of a good layout extremely difficult for most users of such languages. If languages such as HPF are to find general acceptance, the need for data layout selection support has to be addressed. We beleive that the appropriate way to provide the needed support is through a tool that generates data layout specifications automatically. This article discusses the design and implementation of a data layout selection tool that generates HPF-style data layout specifications automatically. Because layout is done in a tool that is not embedded in the target compiler and hence will be run only a few times during the tuning phase of an application, it can use techniques such as integer programming that may be considered too computationally expensive for inclusion in production compilers. The proposed framework for automatic data layout selection builds and examines search spaces of candidate data layouts. A candidate layout is an efficient layout for some part of the program. After the generation of search spaces, a single candidate layout is selected for each program part, resulting in a data layout for the entire program. A good overall data layout may require the remapping of arrays between program parts. A performance estimator based on a compiler model, an execution model, and a machine model are needed to predict the execution time of each candidate layout and the costs of possible remappings between candidate data layouts. In the proposed framework, instances of NP-complete problems are solved during the construction of candidate layout search spaces and the final selection of candidate layouts from each search space. Rather than resorting to heuristics, the framework capitalizes on state-of-the-art 0-1 integer programming technology to compute optimal solutions of these NP-complete problems. A prototype data layout assistant tool based on our framework has been implemented as part of the D system currently under development at Rice University. The article reports preliminary experimental results. The results indicate that the framework is efficient and allows the generation of data layouts of high quality.
A type system for Java bytecode subroutines
Authors: Stata Raymie , Abadi Martin
Published: October 2002

Java is typically compiled into an intermediate language, JVML, that
is interpreted by the Java Virtual Machine. Because mobile JVML code is not always trusted, a bytecode verifier enforces static constraints that prevent various dynamic errors. Given the importance of the bytecode verifier for security, its current descriptions are inadequate. This article proposes using typing rules to describe the bytecode verifier because they are more precise than prose, clearer than code, and easier to reason about than either. JVML has a subroutine construct which is used for the compilation of Java's try-finally statement. Subroutines are a major source of complexity for the bytecode verifier because they are not obviously last-in/first-out and because they require a kind of polymorphism. Focusing on subroutines, we isolate an interesting, small subset of JVML. We give typing rules for this subset and prove their correctness. Our type system constitutes a sound basis for bytecode verification and a rational reconstruction of a delicate part of Sun's bytecode verifier.
From system F to typed assembly language
Authors: Morrisett Greg , Walker David , Crary Karl , Glew Neal
Published: October 2002

We motivate the design of typed assembly language (TAL) and present a type-preserving ttranslation from Systemn F to TAL. The typed assembly language we pressent is based on a conventional RISC assembly language, but its static type sytem provides support for enforcing high-level language abstratctions, such as closures, tuples, and user-defined abstract data types. The type system ensures that well-typed programs cannot violatet these abstractionsl In addition, the typing constructs admit many low-level compiler optimiztaions. Our translation to TAL is specified as a sequence of type-preserving transformations, including CPS and closure conversion phases; type-correct source programs are mapped to type-correct assembly language. A key contribution is an approach to polymorphic closure conversion that is considerably simpler than previous work. The compiler and typed assembly lanugage provide a fully automatic way to produce certified code, suitable for use in systems where unstrusted and potentially malicious code must be checked for safety before execution.
Linear scan register allocation
Authors: Poletto Massimiliano , Sarkar Vivek
Published: October 2002

We describe a new algorithm for fast global register allocation called
linear scan
. This algorithm is not based on graph coloring, but allocates registers to variables in a single linear-time scan of the variables' live ranges. The linear scan algorithm is considerably faster than algorithms based on graph coloring, is simple to implement, and results in code that is almost as efficient as that obtained using more complex and time-consuming register allocators based on graph coloring. The algorithm is of interest in applications where compile time is a concern, such as dynamic compilation systems, “just-in-time” compilers, and interactive development environments.
Detecting global variables in denotational specifications
Authors: Schmidt David A.
Published: October 2002

Sufficient criteria are given for replacing all occurrences of the store argument in a Scott-Strachey denotational definition of a programming language by a single global variable. The criteria and transformation are useful for transforming denotational definitions into compilers and interpreters for imperative machines, for optimizing applicative programs, and for judging the suitability of semantic notations for describing imperative languages. An example transformation of a semantics of a repeat-loop language to one which uses a global store variable is given to illustrate the technique.
Integrating object-oriented programming and protected objects in Ada 95
Authors: Wellings A. J. , Johnson B. , Sanden B. , Kienzle J. , Wolf T. , Michell S.
Published: October 2002

Integrating concurrent and object-oriented programming has been an active research topic since the late 1980's. There is a now a plethora of methods for achieving this integration. The majority of approaches have taken a sequential object-oriented language and made it concurrent. A few approaches have taken a concurrent language and made it object-oriented. The most important of this latter class is the Ada 95 language, which is an extension to the object-based concurrent programming language Ada 83. Arguably, Ada 95 does not fully integrate its models of concurrency and object-oriented programming. For example, neither tasks nor protected objects are extensible. This article discusses ways in which protected objects can be made more extensible.
A fast algorithm for finding dominators in a flowgraph
Authors: Lengauer Thomas , Tarjan Robert Endre
Published: October 2002

A fast algorithm for finding dominators in a flowgraph is presented. The algorithm uses
depth-first search and an efficient method of computing functions defined on paths in trees. A simple implementation of the algorithm runs in
O
(
m
log
n
) time, where
m
is the number of edges and
n
is the number of vertices in the problem graph. A more sophisticated implementation runs in
O
(
m
α(
m
,
n
)) time, where α(
m
,
n
) is a functional inverse of Ackermann's function.

Both versions of the algorithm were implemented in Algol W, a Stanford University version of Algol, and tested on an IBM 370/168. The programs were compared with an implementation by Purdom and Moore of a straightforward
O
(
mn
)-time algorithm, and with a bit vector algorithm described by Aho and Ullman. The fast algorithm beat the straightforward algorithm and the bit vector algorithm on all but the smallest graphs tested.
Simplification by Cooperating Decision Procedures
Authors: Nelson Greg , Oppen Derek C.
Published: October 2002

A method for combining decision procedures for several theories into a single decision procedure for their combination is described, and a simplifier based on this method is discussed. The simplifier finds a normal form for any expression formed from individual variables, the usual Boolean connectives, the equality predicate =, the conditional function if-then-else, the integers, the arithmetic functions and predicates +, -, and ≤, the Lisp functions and predicates car, cdr, cons, and atom, the functions store and select for storing into and selecting from arrays, and uninterpreted function symbols. If the expression is a theorem it is simplified to the constant true, so the simplifier can be used as a decision procedure for the quantifier-free theory containing these functions and predicates. The simplifier is currently used in the Stanford Pascal Verifier.
A Deductive Approach to Program Synthesis
Authors: Manna Zohar , Waldinger Richard
Published: October 2002

Program synthesis is the systematic derivation of a program from a given specification. A deductive approach to program synthesis is presented for the construction of recursive programs. This approach regards program synthesis as a theorem-proving task and relies on a theorem-proving method that combines the features of transformation rules, unification, and mathematical induction within a single framework.
Standard fixpoint iteration for Java bytecode verification
Authors: Qian Zhenyu
Published: October 2002

Java bytecode verification forms the basis for Java-based Internet security and needs a rigorous description. One important aspect of bytecode verification is to check if a Java Virtual Machine (JVM) program is statically well-typed. So far, several formal specifications have been proposed to define what the static well-typedness means. This paper takes a step further and presents a chaotic fixpoint iteration, which represents a family of fixpoint computation strategies to compute a least type for each JVM program within a finite number of iteration steps. Since a transfer function in the iteration is not monotone, we choose to follow the example of a nonstandard fixpoint theorem, which requires that all transfer functions are increasing, and monotone in case the bigger element is already a fixpoint. The resulting least type is the artificial top element if and only if he JVM program is not statically well-typed. The iteration is standard and close to Sun's informal specification and most commercial bytecode verifiers.
An overview of the SR language and implementation
Authors: Andrews Gregory R. , Coffin Michael , Elshoff Irving , Nilsen Kelvin , Townsend Gregg , Olsson Ronald A. , Purdin Titus
Published: October 2002

SR is a language for programming distributed systems ranging from operating systems to application programs. On the basis of our experience with the initial version, the language has evolved considerably. In this paper we describe the current version of SR and give an overview of its implementation. The main language constructs are still resources and operations. Resources encapsulate processes and variables that they share; operations provide the primary mechanism for process interaction. One way in which SR has changed is that both resources and processes are now created dynamically. Another change is that inheritance is supported. A third change is that the mechanisms for operation invocation—call and send—and operation implementation—proc and in—have been extended and integrated. Consequently, all of local and remote procedure call, rendezvous, dynamic process creation, asynchronous message passing, multicast, and semaphores are supported. We have found this flexibility to be very useful for distributed programming. Moreover, by basing SR on a small number of well-integrated concepts, the language has proved easy to learn and use, and it has a reasonably efficient implementation.
Systems semantics: principles, applications, and implementation
Authors: Boute Ray
Published: October 2002

Systems semantics extends the denotational semantics of programming languages to a semantics for the description of arbitrary systems, including objects that are not computations in any sense. By defining different meaning functions, the same formal description may be used to denote different system properties, such as structure, behavior, component cost, and performance aspects (e.g., timing).

The definition of these semantic functions also provides guidance in language design, in particular for the match between language constructs and the system concepts to be expressed. Aiming at compositionality ensures useful properties for formal manipulation. In this fashion, the meaning functions can be made sufficiently simple to serve not only as a direct implementation on a machine but also as rules for reasoning about systems in a transformational manner. As the applications show, however, compositionality can be ensured only through careful consideration of the characteristics of the flow of information inside the system.

Two classes of application are discussed:

Unidirectional systems, in particular digital systems without feedback (combinational) and with feedback (sequential), and a certain class of analog systems.

Nonunidirectional systems, in particular two-port analog networks. The emphasis will be on the functional style of description and on formal reasoning (theorem proving, derivation of properties).

Implementation and rapid prototyping strategies in various system description environments are also briefly discussed. These would permit the concepts of system semantics to be explored without the need for a complete implementation.
Side effects and aliasing can have simple axiomatic descriptions
Authors: Boehm Hans-Juergen
Published: October 2002

We present a different style of axiomatic definition for programming languages. It is oriented toward imperative languages, such as Algol 68, that do not distinguish between statements and expressions. Rather than basing the logic on a notion of pre- or postcondition, we use the value of a programming language expression as the underlying primitive.

A number of language constructs are examined in this framework. We argue that this style of definition gives us a significantly different view of the notion of “easy axiomatixability.” Side effects in expressions as well as aliasing between variables are shown to be “easily axiomatizable” in our system.
Efficient demand-driven evaluation. Part 2
Authors: Pingali Keshav , Arvind
Published: October 2002

In Part 1 of this paper [5], we presented a scheme whereby a compiler could propagate demands through programs in a powerful stream language L. A data-driven evaluation of the transformed program performed exactly the same computation as a demand-driven evaluation of the original program. In this paper we explore a different transformation, which trades the complexity of demand propagation for a
bounded
amount of extra computation on some data lines.
An indexed model of recursive types for foundational proof-carrying code
Authors: Appel Andrew W. , McAllester David
Published: October 2002

The proofs of "traditional" proof carrying code (PCC) are type-specialized in the sense that they require axioms about a specific type system. In contrast, the proofs of foundational PCC explicitly define all required types and explicitly prove all the required properties of those types assuming only a fixed foundation of mathematics such as higher-order logic. Foundational PCC is both more flexible and more secure than type-specialized PCC.For foundational PCC we need semantic models of type systems on von Neumann machines. Previous models have been either too weak (lacking general recursive types and first-class function-pointers), too complex (requiring machine-checkable proofs of large bodies of computability theory), or not obviously applicable to von Neumann machines. Our new model is strong, simple, and works either in λ-calculus or on Pentiums.
Emerging trends in business analytics
Authors: Kohavi Ron , Rothleder Neal J. , Simoudis Evangelos
Published: October 2002

The goal is business effectiveness through 'verticalization,' usability, and integration with operational systems.
CHARMS
Authors: Grinspun Eitan , Krysl Petr , Schröder Peter
Published: October 2002

Finite element solvers are a basic component of simulation applications; they are common in computer graphics, engineering, and medical simulations. Although
adaptive
solvers can be of great value in reducing the often high computational cost of simulations they are not employed broadly. Indeed, building adaptive solvers can be a daunting task especially for 3D finite elements. In this paper we are introducing a new approach to produce
conforming, hierarchical, adaptive refinement methods
(CHARMS). The basic principle of our approach is to refine basis functions, not elements. This removes a number of implementation headaches associated with other approaches and is a general technique independent of domain dimension (here 2D and 3D), element type (e.g., triangle, quad, tetrahedron, hexahedron), and basis function order (piece-wise linear, higher order B-splines, Loop subdivision, etc.). The (un-)refinement algorithms are simple and require little in terms of data structure support. We demonstrate the versatility of our new approach through 2D and 3D examples, including medical applications and thin-shell animations.
Pointshop 3D
Authors: Zwicker Matthias , Pauly Mark , Knoll Oliver , Gross Markus
Published: October 2002

We present a system for interactive shape and appearance editing of 3D point-sampled geometry. By generalizing conventional 2D pixel editors, our system supports a great variety of different interaction techniques to alter shape and appearance of 3D point models, including cleaning, texturing, sculpting, carving, filtering, and resampling. One key ingredient of our framework is a novel concept for interactive point cloud parameterization allowing for distortion minimal and aliasing-free texture mapping. A second one is a dynamic, adaptive resampling method which builds upon a continuous reconstruction of the model surface and its attributes. These techniques allow us to transfer the full functionality of 2D image editing operations to the irregular 3D point setting. Our system reads, processes, and writes point-sampled models without intermediate tesselation. It is intended to complement existing low cost 3D scanners and point rendering pipelines for efficient 3D content creation.
Interactive geometry remeshing
Authors: Alliez Pierre , Meyer Mark , Desbrun Mathieu
Published: October 2002

We present a novel technique, both flexible and efficient, for interactive remeshing of irregular geometry. First, the original (arbitrary genus) mesh is substituted by a series of 2D maps in parameter space. Using these maps, our algorithm is then able to take advantage of established signal processing and halftoning tools that offer real-time interaction and intricate control. The user can easily combine these maps to create a control map --- a map which controls the sampling density over the surface patch. This map is then sampled at interactive rates allowing the user to easily design a tailored resampling. Once this sampling is complete, a Delaunay triangulation and fast optimization are performed to perfect the final mesh.As a result, our remeshing technique is extremely versatile and general, being able to produce arbitrarily complex meshes with a variety of properties including: uniformity, regularity, semi-regularity, curvature sensitive resampling, and feature preservation. We provide a high level of control over the sampling distribution allowing the user to interactively custom design the mesh based on their requirements thereby increasing their productivity in creating a wide variety of meshes.
Geometry images
Authors: Gu Xianfeng , Gortler Steven J. , Hoppe Hugues
Published: October 2002

Surface geometry is often modeled with irregular triangle meshes. The process of remeshing refers to approximating such geometry using a mesh with (semi)-regular connectivity, which has advantages for many graphics applications. However, current techniques for remeshing arbitrary surfaces create only
semi-regular
meshes. The original mesh is typically decomposed into a set of disk-like charts, onto which the geometry is parametrized and sampled. In this paper, we propose to remesh an arbitrary surface onto a
completely regular
structure we call a
geometry image.
It captures geometry as a simple 2D array of quantized points. Surface signals like normals and colors are stored in similar 2D arrays using the same implicit surface parametrization --- texture coordinates are absent. To create a geometry image, we cut an arbitrary mesh along a network of edge paths, and parametrize the resulting single chart onto a square. Geometry images can be encoded using traditional image compression algorithms, such as wavelet-based coders.
Turning to the masters
Authors: Bregler Christoph , Loeb Lorie , Chuang Erika , Deshpande Hrishi
Published: October 2002

In this paper, we present a technique we call "cartoon capture and retargeting" which we use to track the motion from traditionally animated cartoons and retarget it onto 3-D models, 2-D drawings, and photographs. By using animation as the source, we can produce new animations that are expressive, exaggerated or non-realistic.Cartoon capture transforms a digitized cartoon into a cartoon motion representation. Using a combination of affine transformation and key-shape interpolation, cartoon capture tracks non-rigid shape changes in cartoon layers. Cartoon retargeting translates this information into different output media. The result is an animation with a new look but with the movement of the original cartoon.
Interactive global illumination in dynamic scenes
Authors: Tole Parag , Pellacini Fabio , Walter Bruce , Greenberg Donald P.
Published: October 2002

In this paper, we present a system for interactive computation of global illumination in dynamic scenes. Our system uses a novel scheme for caching the results of a high quality pixel-based renderer such as a bidirectional path tracer. The Shading Cache is an object-space hierarchical subdivision mesh with lazily computed shading values at its vertices. A high frame rate display is generated from the Shading Cache using hardware-based interpolation and texture mapping. An image space sampling scheme refines the Shading Cache in regions that have the most interpolation error or those that are most likely to be affected by object or camera motion.Our system handles dynamic scenes and moving light sources efficiently, providing useful feedback within a few seconds and high quality images within a few tens of seconds, without the need for any pre-computation. Our approach allows us to significantly outperform other interactive systems based on caching ray-tracing samples, especially in dynamic scenes. Based on our results, we believe that the Shading Cache will be an invaluable tool in lighting design and modelling while rendering.
Interactive skeleton-driven dynamic deformations
Authors: Capell Steve , Green Seth , Curless Brian , Duchamp Tom , Popović Zoran
Published: October 2002

This paper presents a framework for the skeleton-driven animation of elastically deformable characters. A character is embedded in a coarse volumetric control lattice, which provides the structure needed to apply the finite element method. To incorporate skeletal controls, we introduce line constraints along the bones of simple skeletons. The bones are made to coincide with edges of the control lattice, which enables us to apply the constraints efficiently using algebraic methods. To accelerate computation, we associate regions of the volumetric mesh with particular bones and perform locally linearized simulations, which are blended at each time step. We define a hierarchical basis on the control lattice, so for detailed interactions the simulation can adapt the level of detail. We demonstrate the ability to animate complex models using simple skeletons and coarse volumetric meshes in a manner that simulates secondary motions at interactive rates.
Octree textures
Authors: Benson David , Davis Joel
Published: October 2002

Texturing using a set of two dimensional image maps is an established and widespread practice. However, it has many limitations. Parameterizing a model in texture space can be very difficult, particularly with representations such as implicit surfaces, subdivision surfaces, and very dense or detailed polygonal meshes. This paper proposes the use of a new kind of texture based on an octree, which needs no parameterization other than the surface itself, and yet has similar storage requirements to 2D maps. In addition, it offers adaptive detail, regular sampling over the surface, and continuity across surface boundaries. The paper addresses texture creation, painting, storage, processing, and rendering with octree textures.
Information management in the aftermath of 9/11
Authors: Miller Ralph R.
Published: October 2002

The right to an individual's privacy and the right of a nation to protect itself hang in the balance.
An overview of the sparse basic linear algebra subprograms
Authors: Duff Iain S. , Heroux Michael A. , Pozo Roldan
Published: October 2002

We discuss the interface design for the Sparse Basic Linear Algebra Subprograms (BLAS), the kernels in the recent standard from the BLAS Technical Forum that are concerned with unstructured sparse matrices. The motivation for such a standard is to encourage portable programming while allowing for library-specific optimizations. In particular, we show how this interface can shield one from concern over the specific storage scheme for the sparse matrix. This design makes it easy to add further functionality to the sparse BLAS in the future.We illustrate the use of the Sparse BLAS with examples in the three supported programming languages, Fortran 95, Fortran 77, and C.
Locally adaptive dimensionality reduction for indexing large time series databases
Authors: Chakrabarti Kaushik , Keogh Eamonn , Mehrotra Sharad , Pazzani Michael
Published: October 2002

Similarity search in large time series databases has attracted much research interest recently. It is a difficult problem because of the typically high dimensionality of the data. The most promising solutions involve performing dimensionality reduction on the data, then indexing the reduced data with a multidimensional index structure. Many dimensionality reduction techniques have been proposed, including Singular Value Decomposition (SVD), the Discrete Fourier transform (DFT), and the Discrete Wavelet Transform (DWT). In this article, we introduce a new dimensionality reduction technique, which we call Adaptive Piecewise Constant Approximation (APCA). While previous techniques (e.g., SVD, DFT and DWT) choose a common representation for all the items in the database that minimizes the global reconstruction error, APCA approximates each time series by a set of constant value segments of varying lengths such that their individual reconstruction errors are minimal. We show how APCA can be indexed using a multidimensional index structure. We propose two distance measures in the indexed space that exploit the high fidelity of APCA for fast searching: a lower bounding Euclidean distance approximation, and a non-lower-bounding, but very tight, Euclidean distance approximation, and show how they can support fast exact searching and even faster approximate searching on the same index structure. We theoretically and empirically compare APCA to all the other techniques and demonstrate its superiority.
A survey of graph layout problems
Authors: Díaz Josep , Petit Jordi , Serna Maria
Published: October 2002

Graph layout problems are a particular class of combinatorial optimization problems whose goal is to find a linear layout of an input graph in such way that a certain objective cost is optimized. This survey considers their motivation, complexity, approximation properties, upper and lower bounds, heuristics and probabilistic analysis on random graphs. The result is a complete view of the current state of the art with respect to layout problems from an algorithmic point of view.
Enterprise services
Authors: Fremantle Paul , Weerawarana Sanjiva , Khalaf Rania
Published: October 2002

Examining the emerging field of Web Services and how it is integrated into existing enterprise infrastructures.
Creativity support tools
Authors: Shneiderman Ben
Published: October 2002

Establishing a framework of activities for creative work.
Typed representation of objects by functions
Authors: Steensgaard-Madsen J.
Published: October 2002

A systematic representation of objects grouped into types by constructions similar to the composition of sets in mathematics is proposed. The representation is by lambda expressions, which supports the representation of objects from function spaces. The representation is related to a rather conventional language of type descriptions in a way that is believed to be new. Ordinary control-expressions (i.e.,case- and let-expressions) are derived from the proposed representation.
Type extension through polymorphism
Authors: Burton F. Warren
Published: October 2002

A record data type can be
extended
by addition of more fields. The extended type is a subtype of the original, in that any value of the extended type can be regarded as a value of the original type by ignoring the additional fields. This results in a type hierarchy.

Milner [3] has proposed a polymorphic type system. With the Milner approach, the type of a function may contain type variables. This also results in a type hierarchy.

In a language with a polymorphic type system, if it is anticipated that a record type will need to be extended, then the record type can be defined to have a dummy
extension field
. In the parent type, the extension field will have
null
contents of type
void
. The type of the extension field can differ with different subtypes.

The approach can be extended to allow a type to be subtype of two or more parent types.

To a limited extent, this approach can be used in Ada and other languages with generic program units.
Linearizability: a correctness condition for concurrent objects
Authors: Herlihy Maurice P. , Wing Jeannette M.
Published: October 2002

A concurrent object is a data object shared by concurrent processes. Linearizability is a correctness condition for concurrent objects that exploits the semantics of abstract data types. It permits a high degree of concurrency, yet it permits programmers to specify and reason about concurrent objects using known techniques from the sequential domain. Linearizability provides the illusion that each operation applied by concurrent processes takes effect instantaneously at some point between its invocation and its response, implying that the meaning of a concurrent object's operations can be given by pre- and post-conditions. This paper defines linearizability, compares it to other correctness conditions, presents and demonstrates a method for proving the correctness of implementations, and shows how to reason about concurrent objects, given they are linearizable.
Membrane Traffic Exploited by Protein Toxins
Authors: Sandvig Kirsten , van Deurs Bo
Published: October 2002

▪ Abstract  A large number of protein toxins having enzymatically active A- and B-moieties that bind to cell surface receptors must be endocytosed before the A-moiety is translocated into the cytosol where it exerts its cytotoxic action. The accumulated information about the most well-studied toxins has provided a detailed picture of how they exploit the membrane trafficking systems of cells, and studies of toxin trafficking have revealed the existance of new pathways. The complexity of different endocytic mechanisms, as well as the multiple routes between endosomes and the Golgi apparatus and retrogradely to the endoplasmic reticulum (ER), are being unravelled by investigations of how toxins gain access to their targets. With increasing information about the internalization and intracellular trafficking of these opportunistic toxins, new avenues have been opened for their application in areas of medicine such as drug delivery and therapy.
Type III Protein Secretion in Yersinia Species
Authors: Ramamurthi Kumaran S. , Schneewind Olaf
Published: October 2002

▪ Abstract  The type III mechanism of protein secretion is a pathogenic strategy shared by a number of gram-negative pathogens of plants and animals that has evolved in order to inject virulence proteins into the cytosol of target eukaryotic cells. The pathogens of the Yersinia genus represent a model system where much progress has been made in understanding this secretion pathway. Herein, we review what has been recently learned in yersiniae about the various environmental signals that induce type III secretion, how the synthesis of secretion substrates is regulated, and how such a diverse group of proteins is recognized as a substrate for secretion.
Autoinhibitory Domains: Modular Effectors of Cellular Regulation
Authors: Pufall Miles A. , Graves Barbara J.
Published: October 2002

▪ Abstract  Autoinhibitory domains are regions of proteins that negatively regulate the function of other domains via intramolecular interactions. Autoinhibition is a potent regulatory mechanism that provides tight “on-site” repression. The discovery of autoinhibition generates valuable clues to how a protein is regulated within a biological context. Mechanisms that counteract the autoinhibition, including proteolysis, post-translational modifications, as well as addition of proteins or small molecules in trans, often represent central regulatory pathways. In this review, we document the diversity of instances in which autoinhibition acts in cell regulation. Seven well-characterized examples (e.g., σ70, Ets-1, ERM, SNARE and WASP proteins, SREBP, Src) are covered in detail. Over thirty additional examples are listed. We present experimental approaches to characterize autoinhibitory domains and discuss the implications of this widespread phenomenon for biological regulation in both the normal and diseased states.
Proteolysis and Sterol Regulation
Authors: Hampton Randolph Y.
Published: October 2002

▪ Abstract  The mammalian cell continuously adjusts its sterol content by regulating levels of key sterol synthetic enzymes and levels of LDL receptors that mediate uptake of cholesterol-laden particles. Control is brought about by sterol-regulated transcription of relevant genes and by regulated degradation of the committed step enzyme HMG-CoA reductase (HMGR). Current work has revealed that proteolysis is at the heart of each of these mechanistically distinct axes. Transcriptional control is effected by regulated cleavage of the membrane-bound transcription factor sterol regulatory element binding protein (SREBP), and HMGR degradation is brought about by ubiquitin-mediated degradation. In each case, ongoing cell biological processes are being harnessed to bring about regulation. The secretory pathway plays a central role in allowing sterol-mediated control of transcription. The constitutively active endoplasmic reticulum (ER) quality control apparatus is employed to bring about regulated destruction of HMGR. This review describes the methods and results of various studies to understand the mechanisms and molecules involved in these distinct but interrelated aspects of sterol regulation and the intriguing similarities that appear to exist at the levels of protein sequence and cell biology.
Membrane Fusion in Eukaryotic Cells
Authors: Mayer Andreas
Published: October 2002

▪ Abstract  Membrane fusion is a fundamental biochemical reaction and the final step in all vesicular trafficking events. It is crucial for the transfer of proteins and lipids between different compartments and for exo- and endocytic traffic of signaling molecules and receptors. It leads to the reconstruction of organelles such as the Golgi or the nuclear envelope, which decay into fragments during mitosis. Hence, controlled membrane fusion reactions are indispensible for the compartmental organization of eukaryotic cells; for their communication with the environment via hormones, neurotransmitters, growth factors, and receptors; and for the integration of cells into multicellular organisms. Intracellular pathogenic bacteria, such as Mycobacteria or Salmonellae, have developed means to control fusion reactions in their host cells. They persist in phagosomes whose fusion with lysosomes they actively suppress—a means to ensure survival inside host cells. The past decade has witnessed rapid progress in the elucidation of parts of the molecular machinery involved in these membrane fusion reactions. Whereas some elements of the fusion apparatus are remarkably similar in several compartments, there is an equally striking divergence of others. The purpose of this review is to highlight common features of different fusion reactions and the concepts that emerged from them but also to stress the differences and challenge parts of the current hypotheses. This review covers only the endoplasmic fusion reactions mentioned above, i.e., reactions initiated by contacts of membranes with their cytoplasmic faces. Ectoplasmic fusion events, which depend on an initial contact of the fusion partners via the membrane surfaces exposed to the surrounding medium are not discussed, nor are topics such as the entry of enveloped viruses, formation of syncytia, gamete fusion, or vesicle scission (a fusion reaction that leads to the fission of, e.g., transport vesicles).
Angiographic Findings of the Multicenter Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL)
Authors: Regar E. , Serruys P.W. , Bode C. , Holubarsch C. , Guermonprez J.L. , Wijns W. , Bartorelli A. , Constantini C. , Degertekin M. , Tanabe K. , Disco C. , Wuelfert E. , Morice M.C.
Published: October 2002

Background—

Restenosis remains the major limitation of coronary catheter-based intervention. In small vessels, the amount of neointimal tissue is disproportionately greater than the vessel caliber, resulting in higher restenosis rates. In the Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL) trial, ≈40% of the vessels were small (<2.5 mm). The present study evaluates the relationship between angiographic outcome and vessel diameter for sirolimus-eluting stents.

Methods and Results—

Patients were randomized to receive either an 18-mm bare metal Bx VELOCITY (BS group, n=118), or a sirolimus-eluting Bx VELOCITY stent (SES group, n=120). Subgroups were stratified into terciles according to their reference diameter (RD; stratum I, RD <2.36 mm; stratum II, RD 2.36 mm to 2.84 mm; stratum III, RD >2.84 mm). At 6-month follow-up, the restenosis rate in the SES group was 0% in all strata (versus 35%, 26%, and 20%, respectively, in the BS group). In-stent late loss was 0.01±0.25 versus 0.80±0.43 mm in stratum I, 0.01±0.38 versus 0.88±0.57 mm in stratum II, and −0.06±0.35 versus 0.74±0.57 mm in stratum III (SES versus BS). In SES, the minimal lumen diameter (MLD) remained unchanged (Δ −0.72 to 0.72 mm) in 97% of the lesions and increased (=late gain, ΔMLD <−0.72 mm) in 3% of the lesions. Multivariate predictors for late loss were treatment allocation (
P
<0.001) and postprocedural MLD (
P
= 0.008).

Conclusions—

Sirolimus-eluting stents prevent neointimal proliferation and late lumen loss irrespective of the vessel diameter. The classic inverse relationship between vessel diameter and restenosis rate was seen in the bare stent group but not in the sirolimus-eluting stent group.
Twisted Bodies: Aspects of Female Contortionism in the Letters of a Connoisseur
Authors: Toepfer Karl
Published: October 2002

Investigating a little known art—sexual, perverse, fascinating—as revealed in the letters and photographs of Eduardo Titus, a man obsessed with bodies pliant yet strong, vulnerable yet bold.
To explore the pathogenesis and scientific connotation of non‐alcoholic fatty liver based on the theory of turbid toxin of traditional Chinese medicine
Authors: Kou Guanjun , Luo Hongwei , Huang Xing , Bai Mingxue , Cao Ke , Ma Hongyu , Lv Xiang
Published: January 2024

Non‐alcoholic fatty liver disease (NAFLD) is a metabolic liver disease characterized by the accumulation of excessive liver lipids without alcohol‐induced damage. It has emerged as a significant global health issue. A recent research has indicated that dysregulation of lipid decomposition, uptake, production, oxidation, and secretion causes alterations in various types of lipids, leading to organelle dysfunction and metabolic signaling pathway impairment. Scholars propose that turbid toxin is crucial in the pathogenesis of NAFLD. This article elucidates the meaning of turbid toxin in conjunction with the current literature and analyzes the modern pathophysiological mechanism underlying the development of NAFLD, including turbid toxic substance production, related organelle involvement, biological processes, and pathways, ultimately leading to disease outcomes. The relationship between traditional Chinese medicine and the turbid toxin is also explored to establish a foundation for further mechanistic research on NAFLD.
Unclosing Premature Mortality Gap Among Patients With Gout in the US General Population, Independent of Serum Urate and Atherosclerotic Cardiovascular Risk Factors
Authors: McCormick Natalie , Lin Kehuan , Yokose Chio , Lu Na , Zhang Yuqing , Choi Hyon K.
Published: January 2024

Objective

Gout flares are followed by transient major cardiovascular (CV) risk, implicating the role of inflammation; the aim of this study was to determine whether premature mortality rates in patients with gout and CV risk are independent of serum urate (SU) and atherosclerotic CV disease (ASCVD) risk factors.

Methods

Using serial US nationwide prospective cohorts, we evaluated the independent association of prevalent gout with all‐cause and CV mortality, adjusting for SU, ASCVD risk factors, comorbidities, medications, and kidney function and compared mortality rates between the early (1988–1994 baseline) and late cohorts (2007–2016 baseline). We replicated late cohort findings among patients with gout in a nationwide UK cohort (2006–2010 baseline).

Results

Adjusted hazard ratios (HRs) for mortality rates in patients with prevalent gout were similar in early and late US cohorts (1.20 [1.03–1.40] and 1.19 [1.04–1.37], respectively); HRs with further adjustment for SU were 1.19 (1.02–1.38) and 1.19 (1.03–1.37), respectively. Adjusted HR among patients with gout from the UK late cohort was 1.61 (1.47–1.75); these associations were larger among women (P = 0.04) and prominent among Black individuals. Adjusted HR for CV mortality rates in the late US cohort was 1.39 (1.09–1.78); those for circulatory, CV, and coronary heart disease deaths among UK patients with incident gout were 1.48 (1.24–1.76), 1.49 (1.20–1.85), and 1.59 (1.26–1.99), respectively.

Conclusions

Patients with gout experience a persistent mortality gap in all‐cause and CV deaths, even adjusting for SU and ASCVD risk factors, supporting a role for gout‐specific pathways (eg, flare inflammation). These findings suggest gaps in current care, particularly in women and possibly among Black patients.

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“What Came First?” Population‐Based Evaluation of Health Care Encounters for Depression and Anxiety Before and After Inflammatory Arthritis Diagnosis: Disentangling the Relationship Between Mental Health and Arthritis
Authors: Howren Alyssa , Sayre Eric C. , Avina‐Zubieta J. Antonio , Puyat Joseph H. , Da Costa Deborah , Xie Hui , Davidson Eileen , De Vera Mary A.
Published: January 2024

Objective

The study objective was to describe patterns of depression and anxiety health care use before and after diagnosis among patients with inflammatory arthritis (IA), namely, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis.

Methods

We used population‐based linked administrative health data from British Columbia, Canada, to build a cohort of individuals (≥18 years) with incident IA and individuals without IA (“IA‐free controls”) matched on age and sex. We computed the proportion of individuals with IA and controls who had one or more depression or one or more anxiety health care encounters and the use of one or more antidepressants or one or more anxiolytics in each yearly interval five years before and after IA diagnosis. We used multivariable logistic regression models to evaluate the association between IA status and aforementioned depression and anxiety health care use outcomes in each yearly interval.

Results

A total of 80,238 individuals with IA (62.9% female; mean ± SD age 56.2 ± 16.7 years) and 80,238 IA‐free controls (62.9% female; mean ± SD age 56.2 ± 16.6 years) were identified between January 1, 2001, and March 31, 2018. Individuals with IA had significantly increased odds of depression and anxiety health care encounters and dispensation of antidepressants and anxiolytics for each yearly interval before and after diagnosis. Adjusted odds ratios (ORs) were highest in the year immediately before (one or more depression visits: adjusted OR 1.61, 95% confidence interval [CI] 1.55–1.66; one or more anxiolytics: adjusted OR 1.71, 95% CI 1.66–1.77) or after (one or more antidepressants: adjusted OR 1.95, 95% CI 1.89–2.00) IA diagnosis.

Conclusion

Findings suggest a role for depression and anxiety in characterizing the IA prodrome period and generate hypotheses regarding overlapping biopsychosocial processes that link IA and mental health comorbidities.

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Polyoxometalate‐Structured Materials: Molecular Fundamentals and Electrocatalytic Roles in Energy Conversion
Authors: Ma Tian , Yan Rui , Wu Xizheng , Wang Mao , Yin Bo , Li Shuang , Cheng Chong , Thomas Arne
Published: January 2024

Polyoxometalates (POMs), a kind of molecular metal oxide cluster with unique physical–chemical properties, have made essential contributions to creating efficient and robust electrocatalysts in renewable energy systems. Due to the fundamental advantages of POMs, such as the diversity of molecular structures and large numbers of redox active sites, numerous efforts have been devoted to extending their application areas. Up to now, various strategies of assembling POM molecules into superstructures, supporting POMs on heterogeneous substrates, and POMs‐derived metal compounds have been developed for synthesizing electrocatalysts. From a multidisciplinary perspective, the latest advances in creating POM‐structured materials with a unique focus on their molecular fundamentals, electrocatalytic roles, and the recent breakthroughs of POMs and POM‐derived electrocatalysts, are systematically summarized. Notably, this paper focuses on exposing the current states, essences, and mechanisms of how POM‐structured materials influence their electrocatalytic activities and discloses the critical requirements for future developments. The future challenges, objectives, comparisons, and perspectives for creating POM‐structured materials are also systematically discussed. It is anticipated that this review will offer a substantial impact on stimulating interdisciplinary efforts for the prosperities and widespread utilizations of POM‐structured materials in electrocatalysis.