bluuebunny/crossref_metadata_2025 huggingface dataset:
AN EFFICIENT AND SIMPLE QUAD EDGE CONVERSION OF POLYGONAL MAINFOLD OBJECTS
Authors: OH KWANG-MAN , CHOI JEONG-DAN , LEE CHAN-SU , PARK CHAN-JONG , LEE EE-TAEK
Published: July 2002

This paper presents an efficient and simple quad edge conversion method of polygonal (manifold) objects. In a wide variety of applications such as scientific visualization, virtual reality and computer aided geometric design, polygonal objects are expected to be visualized and manipulated within a given time constraint. To achieve these expectations, it is necessary to introduce an efficient data structure as well as high performance graphics hardware and real-time processing techniques such as simplification and level of details. The quad edge data structure is very efficient for handling polygonal objects even though it was originally designed to handle the subdivisions of manifold objects such as Delaunay triangulations and Voronoi diagrams. It, however, has not been used widely because there is no efficient algorithm for quad edge conversion of conventional polygonal objects.

In this paper, we propose a new incremental quad edge conversion algorithm that processes the triangles one by one. Since quad edge has only the splice as a topological operator, the quad edge conversion of each triangle is done by applying three splice operations, a splice per vertex. As an applicaion for the quad edge, a simplification of conventional polygonal objects is implemented. It includes the removing, moving, replacing, and inserting of vertices and edges.
DIRECT MANIPULATION GRAPHICS FOR DATA MINING
Authors: UNWIN ANTONY R. , HOFMANN HEIKE , WILHELM ADALBERT F. X.
Published: July 2002

Data mining has attracted a lot of attention in recent years, but there has been proportionately little attention paid to the contribution data visualisation could make. Checking data quality, monitoring analyses, interpreting and comparing results are all areas in which modern graphics tools have a role to play. Some existing graphical displays can be scaled up successfully, some new displays will be needed, but all should be directly interactive. This paper outlines the key ideas of direct manipulation graphics for data visualisation and describes the contribution they can make to all stages of the data mining process.
Adaptive agent driven routing in communication networks: comparison with a classical approach
Authors: Heusse Martin , Snyers Dominique , Kermarrec Yvon
Published: July 2002

This paper follows an earlier publication in the Advances in Complex Systems journal (Heusse et al., 1998) where we presented a new algorithm based on collaborative agents for routing in communication networks. In this document, we shall investigate its load-balancing capability. This capability is required as a first step to achieve quality of delivery and service. We also compare our new approach to the classical ones and discuss their respective benefits.
Algorithm 721: MTIEU1 and MTIEU2
Authors: Shirts Randall B.
Published: July 2002

Two FORTRAN routines are described which calculate eigenvalues and eigenfunctions of Mathieu's differential equation for noninteger as well as integer order, MTIEU1 uses standard matrix techniques with dimension parameterized to give accuracy in the eigenvalue of one part in 10
12
. MTIEU2 used continued fraction techniques and is optimized to give accuracy in the eigenvalue of one part in 10
14
. The limitations of the algorithms are also discussed and illustrated.
Dynamic fault-tolerant clock synchronization
Authors: Dolev Danny , Halpern Joseph Y. , Simons Barbara , Strong Ray
Published: July 2002

This paper gives two simple efficient distributed algorithms: one for keeping clocks in a network synchronized and one for allowing new processors to join the network with their clocks synchronized. Assuming a fault-tolerant authentication protocol, the algorithms tolerate both link and processor failures of any type. The algorithm for maintaining synchronization works for arbitrary networks (rather than just completely connected networks) and tolerates any number of processor or communication link faults as long as the correct processors remain connected by fault-free paths. It thus represents an improvement over other clock synchronization algorithms such as those of Lamport and Melliar Smith and Welch and Lynch, although, unlike them, it does require an authentication protocol to handle Byzantine faults. Our algorithm for allowing new processors to join requires that more than half the processors be correct, a requirement that is provably necessary.
HCSM
Authors: Cremer James , Kearney Joseph , Papelis Yiannis
Published: July 2002

This paper presents HCSM, a framework for behavior and scenario control based on communicating hierarchical, concurrent state machines. We specify the structure and an operational execution model of HCSM's state machines. Without providing formal semantics, we provide enough detail to implement the state machines and an execution engine to run them. HCSM explicitly marries the reactive (or logical) portion of system behavior with the control activities that produce the behavior. HCSM state machines contain
activity functions
that produce outputs each time a machine is executed. An activity function's output value is computed as a function of accessible external data and the outputs of lower-level state machines. We show how this enables HCSM to model behaviors that involve attending to multiple concurrent concerns and arbitrating between conflicting demands for limited resources. The execution algorithm is free of order dependencies that cause robustness and stability problems in behavior modeling. In addition, we examine the problems of populating virtual environments with autonomous agents exhibiting interesting behavior and of authoring scenarios involving such agents. We argue that HCSM is well suited for modeling the reactive behavior of autonomous agents and for directing such agents to produce desired situations. We demonstrate use of HCSM for modeling vehicle behavior and orchestrating scenarios in the Iowa Driving Simulator, an immersive real-time virtual driving environment.
Self-spacial join selectivity estimation using fractal concepts
Authors: Belussi Alberto , Faloutsos Christos
Published: July 2002

The problem of selectivity estimation for queries of nontraditional databases is still an open issue. In this article, we examine the problem of selectivity estimation for some types of spatial queries in databases containing
real data
. We have shown earlier [Faloutsos and Kamel 1994] that real point sets typically have a
nonuniform
distribution, violating consistently the uniformity and independence assumptions. Moreover, we demonstrated that the theory of fractals can help to describe real point sets. In this article we show how the concept of fractal dimension, i.e., (noninteger) dimension, can lead to the solution for the selectivity estimation problem in spatial databases. Among the infinite family of fractal dimensions, we consider here the Hausdorff fractal dimension
D
0
and the “Correlation” fractal dimension
D
2
. Specifically, we show that (a) the average number of neighbors for a given point set follows a power law, with
D
2
as exponent, and (b) the average number of nonempty range queries follows a power law with
E − D
0
as exponent (
E
is the dimension of the embedding space). We present the formulas to estimate the selectivity for “biased” range queries, for self-spatial joins, and for the average number of nonempty range queries. The result of some experiments on real and synthetic point sets are shown. Our formulas achieve very low relative errors, typically about 10%, versus 40%–100% of the formulas that are based on the uniformity and independence assumptions.
Broadcast protocols to support efficient retrieval from databases by mobile users
Authors: Datta Anindya , VanderMeer Debra E. , Celik Aslihan , Kumar Vijay
Published: July 2002

Mobile computing has the potential for managing information globally. Data management issues in mobile computing have received some attention in recent times, and the design of
adaptive braodcast protocols
has been posed as an important probllem. Such protocols are employed by database servers to decide on the content of bbroadcasts dynamically, in response to client mobility and demand patterns. In this paper we design such protocols and also propose efficient retrieval strategies that may be employed by clients to download information from broadcasts. The goal is to design
cooperative
strategies between server and client to provide access to information in such a way as to minimize energy expenditure by clients. We evaluate the performance of our protocols both analytically and through simulation.
A Remark on Post Normal Systems
Authors: Yasuhara Ann
Published: July 2002

Let
N
(
T
) be the normal system of Post which corresponds to the Thue system,
T
, as in Martin Davis,
Computability and Unsolvability
(McGraw-Hill, New York, 1958), pp. 98-100. It is proved that for any recursively enumerable degree of unsolvability,
D
, there exists a normal system,
N

T
(
D
)

, such that the decision problem for
N

T
(
D
)

is of degree
D
. Define a generalized normal system as a normal system without initial assertion. For such a
GN
the decision problem is to determine for any enunciations
A
and
B
whether or not
A
and
B
are equivalent in
GN
. Thus the generalized system corresponds more naturally to algebraic problems. It is proved that for any recursively enumerable degree of unsolvability,
D
, there exists a generalized normal system,
GN

T
(
D
)

, such that the decision problem for
GN

T
(
D
)

, such that the decision problem for
GN

T
(
D
)

is of degree
D
.
Toeplitz Matrix Inversion: The Algorithm of W. F. Trench
Authors: Zohar Shalhav
Published: July 2002

The algorithm of W. F. Trench for the inversion of Toeplitz matrices is presented with a detailed proof for the case of non-Hermitian matrices. The only condition necessary to insure the validity of the algorithm is that all principal minors be nonzero.
A heuristic problem solving design system for equipment or furniture layouts
Authors: Pfefferkorn Charles E.
Published: July 2002

The Designer Problem Solver (DPS) demonstrates that the computer can perform simple design tasks. In particular, it designs furniture and equipment layouts. This task was chosen because it is simple, well defined, and characteristic of many design tasks in architecture, engineering, urban planning, and natural resource management. These space planning tasks usually involve manipulating two-dimensional representations of objects to create feasible or optimal solutions for problems involving topological and metric spatial constraints. The paper describes extensive tests performed on the program.

DPS is a heuristic problem solver with a planning phase prefixed to it. It uses the planning process to give it a sense of direction, diagnostic procedures to locate difficulties, and remedial actions to recover from difficulties. It uses a convex polygon representation to accurately describe the objects and the layout. This representation allows topological and metric constraints to be tested and the design to be easily updated.

DPS has been applied to 50 problems. While it is slow and limited in scope, the ideas behind it are general. It demonstrates the need for selectivity in controlling search and the methods used to achieve it: task-specific information, planning, diagnostic procedures, remedial actions, and selective alternative generators.
A note on hash linking
Authors: Bobrow Daniel G.
Published: July 2002

In current machine designs, a machine address gives the user direct access to a single piece of information, namely the contents of that machine word. This note is based on the observation that it is often useful to associate additional information, with some (relatively few) address locations determined at run time, without the necessity of preallocating the storage at all possible such addresses. That is, it can be useful to have an effective extra bit, field, or address in some words without every word having to contain a bit (or bits) to mark this as a special case. The key idea is that this extra associated information can be found by a table search. Although it could be found by any search technique (e.g. linear, binary sorted, etc.), we suggest that an appropriate low overhead mechanism is to use hash search on a table in which the key is the address of the cell to be augmented.
A method for composing simple traditional music by computer
Authors: Rader Gary M.
Published: July 2002

A method is described for composing musical rounds by computer. This method uses some music theory plus additional heuristics. Fundamental to the method is a set of productions together with sets of applicability rules and weight rules which operate on the productions deciding when and to what extent they are available for use.

Several rounds generated by the computer implementation of the method are presented. Generally, the resultant music sounds mediocre to the professional although usually pleasing to the layman. It appears that full-blown music theory is not needed for rounds—all the hardware required for structural levels is not necessary for these pieces. The author has tried to address both musicians and computer scientists.
A program for the syntactic analysis of English sentences
Authors: Dewar Hamish , Bratley Paul , Thorne James Peter
Published: July 2002

A program is described which produces syntactic analyses of English sentences with respect to a transformational grammar. The main features of the analyzer are that it uses only a limited dictionary of English words and that it pursues all analysis paths simultaneously while processing the sentence from left to right.

The form of representation used for the dictionary and the grammar is indicated and an outline account is given of the analysis procedure. Techniques for keeping the size of the analysis record within reasonable limits and for avoiding the need for dynamic application of certain transformational rules are described.

A number of examples of output produced by the program are given. The output includes timing information.
A Class Inference Scheme With Dempster-Shafer Theory for Learning Fuzzy-Classifier Systems
Authors: Shiraishi Hiroki , Ishibuchi Hisao , Nakata Masaya
Published: February 2025

The decision-making process significantly influences the predictions of machine learning models. This is especially important in rule-based systems such as Learning Fuzzy-Classifier Systems (LFCSs) where the selection and application of rules directly determine prediction accuracy and reliability. LFCSs combine evolutionary algorithms with supervised learning to optimize fuzzy classification rules, offering enhanced interpretability and robustness. Despite these advantages, research on improving decision-making mechanisms (i.e., class inference schemes) in LFCSs remains limited. Most LFCSs use voting-based or single-winner-based inference schemes. These schemes rely on classification performance on training data and may not perform well on unseen data, risking overfitting. To address these limitations, this article introduces a novel class inference scheme for LFCSs based on the Dempster-Shafer Theory of Evidence (DS theory). The proposed scheme handles uncertainty well. By using the DS theory, the scheme calculates belief masses (i.e., measures of belief) for each specific class and the “I don’t know” state from each fuzzy rule and infers a class from these belief masses. Unlike the conventional schemes, the proposed scheme also considers the “I don’t know” state that reflects uncertainty, thereby improving the transparency and reliability of LFCSs. Applied to a variant of LFCS (i.e., Fuzzy-UCS), the proposed scheme demonstrates statistically significant improvements in terms of test macro F1 scores across 30 real-world datasets compared to conventional voting-based and single-winner-based fuzzy inference schemes. It forms smoother decision boundaries, provides reliable confidence measures, and enhances the robustness and generalizability of LFCSs in real-world applications.
Document architecture and text formatting
Authors: Peels Arno J. H. , Janssen Norbert J. M. , Nawijn Wop
Published: July 2002

The formalization of the architecture of documents and text formatting are the central issues of this paper. Besides a fundamental and theoretical approach toward these topics, an overview is presented of the COBATEF system. The COBATEF system is a context-based text formatting system, for which a software, as well as a hardware, implementation is available.

A unique feature of the system is its automatic text-element recognition mechanism, which is context based and consequently takes advantage of the implicit structure of text. A predefined layout for each type of text element then opens the way for a fully automatic text-processing system in which user control information can be reduced to an absolute minimum.
DITROFF/FFORTID, an adaptation of the UNIX/DITROFF for formatting bidirectional text
Authors: Buchman Cary , Berry Daniel M. , Gonczarowski Jakob
Published: July 2002

DITROFF/FFORTID
, a collection of pre- and postprocessors for the UNIX
DITROFF
(Device Independent Typesetter RunOFF) is described.
DITROFF/FFORTID
permits formatting of text involving a mixture of languages written from left to right and from right to left, such as English and Hebrew. The programs are table driven or macro-generated to permit them to be used for any languages written from left to right and from right to left so long as fonts with the proper character sets can be mounted on a typesetting device supported by
DITROFF
. The preprocessors are set up to permit phonetic, unidirectional input of all of the alphabets needed using only the two alphabets (each case counts as an alphabet) available on the input device. These macro-generated preprocessors can be adjusted to the user's pronunciation, the language's rules about a letter's form, depending on its position in the word, and the language of the user's input keyboard. The postprocessor is set up to properly change direction of formatting when the text switches to a language written in a different direction. The collection of programs is also designed to allow use of any of
DITROFF
's preprocessors, such as
PIC
,
EQN
,
TBL
, and the various device drivers.
Average case selection
Authors: Cunto Walter , Munro J. Ian
Published: July 2002

It is shown that
n
+
k
-
O
(1) comparisons are necessary, on average, to find the
k
th smallest of
n
numbers (
k
⪇
n
/2). This lower bound matches the behavior of the technique of Floyd and Rivest to within a lower-order term. 7
n
/4 ±
o
(
n
) comparisons, on average, are shown to be necessary and sufficient to find the maximum and median of a set. An upper bound of 9
n
/4 ±
o
(
n
) and a lower bound of 2
n
-
o
(
n
) are shown for the max-min-median problem.
Independent general principles for constructing responsive software systems
Authors: Smith Connie U.
Published: July 2002

Three general principles are presented that can be applied in early software life cycle stages for the definition of software requirements and designs with acceptable performance. They are genuine high-level considerations for meeting responsiveness goals without sacrificing understandability and maintainability, and without increasing development time and cost. The principles are derived from the interrelationships of two performance models: a queueing network based on computer system model and an execution graph software model. The performance effect of each of the principles is quantified using the models. Examples are given that illustrate how they can be applied to software systems.
Algorithm 678: BTPEC: sampling from the binomial distribution
Authors: Kachitvichyanukul Voratas , Schmeiser Bruce W.
Published: July 2002

The FORTRAN implementation of an exact, uniformly fast algorithm for generating the binomial, random variables is presented. The algorithm is numerically stable and is faster than other published algorithms. The code uses only standard FORTRAN statements and is portable to most computers; it has been tested on the IBM 370, 3033, 4381, DEC VAX 11/780, SUN 3/50, CDC 6500-6600, ENCORE Multimax, and Apple Mcintosh Plus. A driver program is also included.
Functions and Mechanisms of Histone Modifications in Plants
Authors: Le Huy , Simmons Carl H. , Zhong Xuehua
Published: February 2025

Histones are far more than just the basic units of chromatin. Posttranslational modifications of histone tails have emerged as important regulatory mechanisms for diverse biological processes, including genome organization, gene expression, transposable element suppression, development, and environmental responses. This field is expanding rapidly with the development of new technologies and growing interest from both the basic and translational research communities. The past two decades have witnessed tremendous progress in our understanding of the complex, multilayered regulation and actions of histone modifications in plants. This review summarizes the characteristics, localization, and molecular functions of histone modifications with an emphasis on the well-studied marks in Arabidopsis. We further discuss their functions in developmental transitions and environmental responses as well as their contributions to epigenomic diversity and plasticity. By highlighting the functions and fundamental mechanisms of epigenetic modifications in model plants, this review underscores the potential to harness epigenetic regulation for agricultural improvement.
Alternative Splicing Dynamics in Plant Adaptive Responses to Stress
Authors: Alhabsi Abdulrahman , Ling Yu , Crespi Martin , Reddy Anireddy S.N. , Mahfouz Magdy
Published: February 2025

Plants thrive in dynamic environments by activating sophisticated molecular networks that fine-tune their responses to stress. A key component of these networks is gene regulation at multiple levels, including precursor messenger RNA (pre-mRNA) splicing, which shapes the transcriptome and proteome landscapes. Through the precise action of the spliceosome complex, noncoding introns are removed and coding exons are joined to produce spliced RNA transcripts. While constitutive splicing always generates the same messenger RNA (mRNA), alternative splicing (AS) produces multiple mRNA isoforms from a single pre-mRNA, enriching proteome diversity. Remarkably, 80% of multiexon genes in plants generate multiple isoforms, underscoring the importance of AS in shaping plant development and responses to abiotic and biotic stresses. Recent advances in CRISPR-Cas genome and transcriptome editing technologies offer revolutionary tools to dissect AS regulation at molecular levels, unveiling the functional significance of specific isoforms. In this review, we explore the intricate mechanisms of pre-mRNA splicing and AS in plants, with a focus on stress responses. Additionally, we examine how leveraging AS insights can unlock new opportunities to engineer stress-resilient crops, paving the way for sustainable agriculture in the face of global environmental challenges.
Toward Principles of Brain Network Organization and Function
Authors: Kulkarni Suman , Bassett Dani S.
Published: February 2025

The brain is immensely complex, with diverse components and dynamic interactions building upon one another to orchestrate a wide range of behaviors. Understanding the patterns of these complex interactions and how they are coordinated to support collective neural function is critical for parsing human and animal behavior, treating mental illness, and developing artificial intelligence. Rapid experimental advances in imaging, recording, and perturbing neural systems across various species now provide opportunities to distill underlying principles of brain organization and function. Here, we take stock of recent progress and review methods used in the statistical analysis of brain networks, drawing from fields of statistical physics, network theory, and information theory. Our discussion is organized by scale, starting with models of individual neurons and extending to large-scale networks mapped across brain regions. We then examine organizing principles and constraints that shape the biological structure and function of neural circuits. We conclude with an overview of several critical frontiers, including expanding current models, fostering tighter feedback between theory and experiment, and leveraging perturbative approaches to understand neural systems. Alongside these efforts, we highlight the importance of contextualizing their contributions by linking them to formal accounts of explanation and causation.
Molecular Level Super-Resolution Fluorescence Imaging
Authors: Radmacher Niels , Chizhik Alexey I. , Nevskyi Oleksii , Gallea José Ignacio , Gregor Ingo , Enderlein Jörg
Published: February 2025

Over the last 30 years, fluorescence microscopy, renowned for its sensitivity and specificity, has undergone a revolution in resolving ever-smaller details. This advancement began with stimulated emission depletion (STED) microscopy and progressed with techniques such as photoactivatable localization microscopy and stochastic optical reconstruction microscopy (STORM). Single-molecule localization microscopy (SMLM), which encompasses methods like direct STORM, has significantly enhanced image resolution. Even though its speed is slower than that of STED, SMLM achieves higher resolution by overcoming photobleaching limitations, particularly through DNA point accumulation for imaging in nanoscale topography (DNA-PAINT), which continuously renews fluorescent labels. Additionally, cryo-fluorescence microscopy and advanced techniques like minimal photon fluxes imaging (MINFLUX) have pushed the boundaries toward molecular resolution SMLM. This review discusses the latest developments in SMLM, highlighting methods like resolution enhancement by sequential imaging (RESI) and PAINT-MINFLUX and exploring axial localization techniques such as supercritical angle fluorescence and metal-induced energy transfer. These advancements promise to revolutionize fluorescence microscopy, providing resolution comparable to that of electron microscopy.
The Perils and Promises of Unequal Democracy: Insights from the Sociology of India
Authors: Agarwala Rina , Roychowdhury Poulami
Published: February 2025

Why has India, the world's largest liberal democracy, joined the global turn toward authoritarianism? Drawing on the sociological literature on Indian politics, we argue that India's authoritarian turn emerges from the difficulty of sustaining democracy within an unequal society. The Indian state historically managed this difficulty by balancing the interests of opposed social groups: responding favorably to underprivileged groups’ demands for welfare and rights while simultaneously maintaining elite power and privilege. This approach ensured that everyone enjoyed some wins but also faced some disappointments. For decades, the Indian state's ability to sustain this juggling act was credited for the success of India's liberal democracy. Over time, however, the Indian state's attempt to appease opposed social groups became perilous for democracy. The more the state catered to elite and nonelite demands, the more empowered both groups became to express their dissatisfaction and demand more. Elites, resentful that their privilege was being chipped away to make room for nonelites, and nonelites, frustrated with continued poverty and marginalization at the hands of elites, both began seeking solutions from an alternative, authoritarian-style regime. Recent events suggest that one ray of hope for a more just future in India resides in the social movements that emerged from India's democracy and have recently tried to hold its increasingly authoritarian regime in check. By tracing the social basis of India's democratic fluctuations, sociological literature on India provides important insights for other unequal democracies, where similar elite resentments and nonelite frustrations are fueling authoritarianism.
SUBTRACTIVE CLONING: Past, Present, and Future
Authors: Sagerström C. G. , Sun B. I. , Sive H. L.
Published: July 2002

Subtractive cloning is a powerful technique for isolating genes expressed or present in one cell population but not in another. This method and a related one termed positive selection have their origins in nucleic acid reassociation techniques. We discuss the history of subtractive techniques, and fundamental information about the nucleic acid composition of cells that came out of reassociation analyses. We then explore current techniques for subtractive cloning and positive selection, discussing the merits of each. These techniques include cDNA library–based techniques and PCR-based techniques. Finally, we briefly discuss the future of subtractive cloning and new approaches that may augment or supersede current methods.
3-D Visualization in Biomedical Applications
Authors: Robb Richard A.
Published: July 2002

▪ Abstract  Visualizable objects in biology and medicine extend across a vast range of scale, from individual molecules and cells through the varieties of tissue and interstitial interfaces to complete organs, organ systems, and body parts. These objects include functional attributes of these systems, such as biophysical, biomechanical, and physiological properties. Visualization in three dimensions of such objects and their functions is now possible with the advent of high-resolution tomographic scanners and imaging systems. Medical applications include accurate anatomy and function mapping, enhanced diagnosis, accurate treatment planning and rehearsal, and education/training. Biologic applications include study and analysis of structure-to-function relationships in individual cells and organelles. The potential for revolutionary innovation in the practice of medicine and in biologic investigations lies in direct, fully immersive, real-time multisensory fusion of real and virtual information data streams into online, real-time visualizations available during actual clinical procedures or biological experiments. Current high-performance computing, advanced image processing, and high-fidelity rendering capabilities have facilitated major progress toward realization of these goals. With these advances in hand, there are several important applications of three-dimensional visualization that will have a significant impact on the practice of medicine and on biological research.
Neuroengineering Models of Brain Disease
Authors: Finkel Leif H.
Published: July 2002

▪ Abstract  The techniques of computational simulation have begun to be applied to modeling neurological disease and mental illness. Such neuroengineering models provide a conceptual bridge between molecular/cellular pathology and cognitive performance. We consider models of Alzheimer's disease, Parkinson's disease, and schizophrenia. Each of these diseases involves a disorder of neuromodulation coupled with underlying neuronal pathology. Parallels arising between these models suggests that a common set of computational mechanisms may account for functional loss across a spectrum of brain diseases. In particular, we focus on attractor-based network dynamics and how they arise from neural architectures, on mechanisms for linking sequences of attractor states and their role in cognition, and on the role of neuromodulation in controlling these processes. These studies suggest new approaches to understanding the forebrain circuits underlying cognition, and point toward a new tool for dissecting the pathophysiology of brain disease.
PHOSPHOINOSITIDE LIPIDS AS SIGNALING MOLECULES: Common Themes for Signal Transduction, Cytoskeletal Regulation, and Membrane Trafficking
Authors: Martin T. F. J.
Published: July 2002

▪ Abstract  Signaling roles for phosphoinositides that involve their regulated hydrolysis to generate second messengers have been well characterized. Recent work has revealed additional signaling roles for phosphoinositides that do not involve their hydrolysis. PtdIns 3-P, PtdIns 3,4,5-P3, and PtdIns 4,5-P2function as site-specific signals on membranes that recruit and/or activate proteins for the assembly of spatially localized functional complexes. A large number of phosphoinositide-binding proteins have been identified as the potential effectors for phosphoinositide signals. Common themes of localized signal generation and the spatially localized recruitment of effector proteins appear to underlie mechanisms employed in signal transduction, cytoskeletal, and membrane trafficking events.
Molecular Basis of Celiac Disease
Authors: Sollid Ludvig M.
Published: July 2002

Celiac disease (CD) is an intestinal disorder with multifactorial etiology. HLA and non-HLA genes together with gluten and possibly additional environmental factors are involved in disease development. Evidence suggests that CD4+T cells are central in controlling an immune response to gluten that causes the immunopathology, but the actual mechanisms responsible for the tissue damage are as yet only partly characterized. CD provides a good model for HLA-associated diseases, and insight into the mechanism of this disease may well shed light on oral tolerance in humans. The primary HLA association in the majority of CD patients is with DQ2 and in the minority of patients with DQ8. Gluten-reactive T cells can be isolated from small intestinal biopsies of celiac patients but not of non-celiac controls. DQ2 or DQ8, but not other HLA molecules carried by patients, are the predominant restriction elements for these T cells. Lesion-derived T cells predominantly recognize deamidated gluten peptides. A number of distinct T cell epitopes within gluten exist. DQ2 and DQ8 bind the epitopes so that the glutamic acid residues created by deamidation are accommodated in pockets that have a preference for negatively charged side chains. Evidence indicates that deamidation in vivo is mediated by the enzyme tissue transglutaminase (tTG). Notably, tTG can also cross-link glutamine residues of peptides to lysine residues in other proteins including tTG itself. This may result in the formation of complexes of gluten-tTG. These complexes may permit gluten-reactive T cells to provide help to tTG-specific B cells by a mechanism of intramolecular help, thereby explaining the occurrence of gluten-dependent tTG autoantibodies that is a characteristic feature of active CD.
Collagenous Colitis and Lymphocytic Colitis
Authors: Zeroogian John M. , Chopra Sanjiv
Published: July 2002

Collagenous and lymphocytic colitis are newly recognized causes of choric watery diarrhea that typically affect middle-aged patients. Although endoscopic studies are normal, inflammatory changes and (in the case of collagenous colitis) collagen deposition occur histologically in the colonic mucosa. The pathogenesis of these disorders remains a mystery, but the possible causes are intriguing. Patients may experience spontaneous remissions and relapses, but treatment with sulfasalazine or prednisone is usually effective for patients with distressing symptoms.
TRINUCLEOTIDE INSTABILITY: A Repeating Theme in Human Inherited Disorders
Authors: Gusella, Ph.D James F. , MacDonald, Ph.D Marcy E.
Published: July 2002

▪ Abstract  In recent years, a completely new mechanism of mutation has emerged in a number of disorders that display perplexing and paradoxical features of genetic inheritance. This mechanism involves the expansion and intergenerational instability of stretches of consecutive identical nucleotide triplets that also exist as shorter stable segments on normal chromosomes. The unstable nature of the trinucleotide segments has solved many of the genealogic puzzles in these disorders and has provided a new tool for predictive testing. Treatments for the disorders await a better understanding of the different pathogenic processes that are triggered by various expanded repeats. The existence of numerous other disorders with peculiarities of genetic inheritance suggests that this mutational mechanism may be a major cause of human inherited disease.
RECENT ADVANCES IN SURGERY FOR EMPHYSEMA
Authors: Lefrak, MD Stephen S. , Yusen, MD Roger D. , Trulock, MD Elbert P. , Pohl, RN MHS Mary S. , Patterson, MD Alexander , Cooper, MD Joel D.
Published: July 2002

▪ Abstract  Volume reduction surgery is based on the removal of volume-occupying but nonfunctioning emphysematous lung, which is thought to improve pulmonary elastic recoil. The reduction in thoracic volume may also improve thoracic cage and inspiratory muscle function. In addition, dyspnea is lessened, exercise tolerance is increased, and measured pulmonary function is improved. Alveolar gas exchange may also be improved. Selection criteria include marked airway obstruction secondary to emphysema, marked hyperinflation of the chest wall, and regional heterogeneity in the distribution of the emphysema. The best results are obtained with a bilateral procedure utilizing stapling resection. The two surgical approaches are median sternotomy and video-assisted thoracic surgery.
Chronic Pain
Authors: Russo Cathy M. , Brose William G.
Published: July 2002

Chronic pain is an emotional experience and is defined as pain lasting greater than six months. It is important to understand the neurophysiology of pain in order to treat it. Nociceptors in the periphery travel to the substantia gelatinosa of the spinal cord while secondary and tertiary afferents transmit information from the dorsal horn to the brain. Modification of pain information may take place in these ascending pathways or in descending pathways. Treatment of chronic pain is most successful when it is approached in a multidisciplinary fashion with the focus not only on treatment of underlying etiology, but also on the secondary impacts of pain on the patient's life. The management of chronic pain requires special expertise. Most of the experts in chronic pain assessment and management organize themselves into pain treatment centers. These centers vary widely in their approach to the problem. The most sophisticated is a multidisciplinary center that is university-based and includes teaching and research. Treatment of chronic pain includes a variety of medications, psychological support, and rehabilitation. Multidisciplinary pain management is also an integral part of the palliative care and hospice concept used to treat cancer pain.
The Molecular Ggenetics of the Long QT Syndrome: Genes Causing Fainting and Sudden Death
Authors: Vincent, MD G. Michael
Published: July 2002

The congenital long QT syndrome is an autosomal-dominant genetic disorder of cardiac electrical repolarization. It is caused by mutations of at least six genes, of which four, all encoding for cardiac ion channels, have been identified: KVLQT1, HERG, and Min K encode for cardiac potassium ion channels, and SCN5A encodes for the cardiac sodium ion channel. In each case the altered ion channel function produces prolongation of the action potential and propensity to torsade de pointes ventricular tachycardia. A fifth gene locus is known to be on chromosome 4, but the gene has not been isolated. At least one other gene must exist, and there may be several more. Long QT syndrome is a frequent but often overlooked cause of unexpected syncope and sudden death in children and young adults. Characteristic findings are prolongation of the QT interval and T wave abnormalities on the electrocardiogram. However, the QT interval at presentation is normal about 10% of the time and just borderline prolonged another 30%, so diagnosis may be difficult. Symptoms are syncope and sudden death, typically occurring during exercise or emotional upset. The manifestations vary, depending on the genotype present. The phenotype also probably varies, depending on the specific mutation involved. Phenotypic heterogeneity is also caused by variable penetrance and expressivity.
Root Nodulation and Infection Factors Produced by Rhizobial Bacteria
Authors: Spaink Herman P.
Published: July 2002

▪ Abstract  Rhizobia are soil bacteria that can engage in a symbiosis with leguminous plants that produces nitrogen-fixing root nodules. This symbiosis is based on specific recognition of signal molecules, which are produced by both the bacterial and plant partners. In this review, recognition factors from the bacterial endosymbionts are discussed, with particular attention to secreted and cell surface glycans. Glycans that are discussed include the Nod factors, the extracellular polysaccharides, the lipopolysaccharides, the K-antigens, and the cyclic glucans. Recent advances in the understanding of the biosynthesis, secretion, and regulation of production of these glycans are reviewed, and their functions are compared with glycans produced by other bacteria, such as plant pathogens.
Altered DNA Methylation: A Secondary Mechanism Involved in Carcinogenesis
Authors: Goodman Jay I. , Watson Rebecca E.
Published: July 2002

This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?
ClC AND CFTR CHLORIDE CHANNEL GATING
Authors: Foskett J. Kevin
Published: July 2002

▪ Abstract  Chloride channels are widely expressed and play important roles in cell volume regulation, transepithelial transport, intracellular pH regulation, and membrane excitability. Most chloride channels have yet to be identified at a molecular level. The ClC gene family and the cystic fibrosis transmembrane conductance regulator (CFTR) are distinct chloride channels expressed in many cell types, and mutations in their genes are the cause of several diseases including myotonias, cystic fibrosis, and kidney stones. Because of their molecular definition and roles in disease, these channels have been studied intensively over the past several years. The focus of this review is on recent studies that have provided new insights into the mechanisms governing the opening and closing, i.e. gating, of the ClC and CFTR chloride channels.
GENETICS OF SYNAPTIC VESICLE FUNCTION: Toward the Complete Functional Anatomy of an Organelle
Authors: Fernández-Chacón Rafael , Südhof Thomas C.
Published: July 2002

▪ Abstract  Synaptic transmission starts with the release of neurotransmitters by exocytosis of synaptic vesicles. As a relatively simple organelle with a limited number of components, synaptic vesicles are in principle accessible to complete structural and functional genetic analysis. At present, the majority of synaptic vesicle proteins has been characterized, and many have been genetically analyzed in mice, Drosophila, and Caenorhabditis elegans. These studies have shown that synaptic vesicles contain proteins with diverse structures and functions. Although the genetic studies are as yet unfinished, they promise to lead to a full description of synaptic vesicles as macromolecular machines involved in all aspects of presynaptic neurotransmitter release.
The Prognostic Significance of the DBIL/HDLC Ratio in Patients With Dilated Cardiomyopathy
Authors: Wang Xinyi , Song Qiqi , Zhang Qingqing , Li Xinyi , Wang Jiaqi , Gong Jiantao , Zhang Ziyi , Tan Ning , Ying Tsang Suk , Wong Wing-tak , Ma Dunliang , Jiang Lei
Published: February 2025

Background: In cardiovascular pathology, both direct bilirubin (DBIL) and high‐density lipoprotein cholesterol (HDLC) have been associated with adverse clinical outcomes. However, the prognostic significance of these biomarkers in the context of dilated cardiomyopathy (DCM) remains unclear. To address this gap, this study conducted a retrospective analysis to evaluate the prognostic value of the DBIL/HDLC ratio in patients diagnosed with DCM.

Methods and Results: A total of 986 consecutive DCM patients were retrospectively enrolled from January 2010 to December 2019 and divided into two groups based on the DBIL/HDLC ratio cut‐off value: ≤ 4.45 (n = 483) and > 4.45 (n = 503). Patients with lower DBIL/HDLC (≤ 4.45) experienced lower in‐hospital mortality, long‐term mortality, and major adverse clinical events (MACEs) (0.8%, 32.9%, and 12.2%, respectively) compared to those with higher DBIL/HDLC (> 4.45) (6.4%, 59.1%, and 16.7%, respectively). Multivariate analysis identified DBIL/HDLC as an independent risk factor for long‐term mortality (odds ratio: 1.026; 95% confidence interval (CI): 1.005–1.048; p = 0.016) and all‐cause mortality over a median follow‐up of 67 ± 1.8 months (hazard ratio: 1.011; 95% CI: 1.005–1.018; p < 0.001). The receiver operating characteristic curve showed good discrimination for long‐term mortality (area under the curve (AUC): 0.675; 95% CI: 0.692–0.708; p < 0.001). The Kaplan–Meier survival analysis demonstrated a better prognosis for patients with DBIL/HDLC ≤ 4.45 (log‐rank χ2 = 40.356, p < 0.001). Furthermore, the impact of additional variables on the results was investigated by a subgroup analysis.

Conclusion: The DBIL/HDLC ratio could serve as a simple and cost‐effective tool for evaluating prognosis in DCM.
Unveiling Autism’s Patterns: The Deep Dynamic Levenberg–Marquardt Approach
Authors: Sha Mohemmed , Alqahtani Abdullah , Alsubai Shtwai , Dutta Ashit Kumar
Published: February 2025

ASD (autism spectrum disorder) is a neurodevelopmental disorder affecting people’s social interaction, learning, and communication skills worldwide. It is a behaviorally distinct syndrome that is combined with several unknown and known disorders. The symptoms include sleep disorders, seizures, gastrointestinal tract symptoms, anxiety, wandering, hyperactivity/attention‐deficit disorder, and obesity. Hence, early detection of ASD is significant. However, clinically standardized screening tests are considered a prolonged diagnostic time, which is prone to errors and also leads to a rise in medical costs. Therefore, to decrease the time required for diagnosis and improve the precision of the model, AI (artificial intelligence) (machine learning (ML)) techniques are used to complement other traditional methods. Hence, this study has proposed a modified deep dynamic Levenberg–Marquardt (DDLM) optimized approach, which enhances the accuracy and classifier’s precision for implementing binary classification of children with ASD and children without ASD and tackles the issues in early detection. The process starts by preprocessing the data using label encoding and feature scaling techniques for eradicating irrelevant and noisy data, and then classification proceeds by utilizing the modified DDLM model. The dataset used in the proposed model is an amalgamation of datasets, which are ASD meta‐abundance and GSE113690_Autism_16S_rRNA. Additionally, a comparison of classifiers with three ML‐based algorithms, namely, MLP (multilayer perceptron), NB (naïve Bayes), and XGBoost (extreme gradient boost), is performed to analyze the effectiveness of the proposed system in the binary classification of ASD. The efficacy of the proposed system is evaluated using performance factors such as specificity, precision, F1‐score, accuracy, and recall.