Research papers

Cyclooxygenases: Structural, Cellular, and Molecular Biology

William L. Smith, David L. DeWitt, R. Michael Garavito

The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors. We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression.

EMBOSS: The European Molecular Biology Open Software Suite

Peter Rice, Ian Longden, Alan J. Bleasby

Gene Ontology: tool for the unification of biology

Michael Ashburner, Catherine A. Ball, Judith A. Blake, David Botstein, H. Butler, J. Michael Cherry, Allan Peter Davis, Kara…

Diffraction and low-<i>x</i>physics

J. Bartels

We review issues of low- x physics and hard diffraction at LEP, HERA, and at the Tevatron.

The Biology of Chemokines and their Receptors

Dévora L. Rossi, Albert Zlotnik

During the last five years, the development of bioinformatics and EST databases has been primarily responsible for the identification of many new chemokines and chemokine receptors. The chemokine field has also received considerable attention since chemokine receptors were found to act as co-receptors for HIV infection (1). In addition, chemokines, along with adhesion molecules, are crucial during inflammatory responses for a timely recruitment of specific leukocyte subpopulations to sites of tissue damage. However, chemokines and their receptors are also important in dendritic cell maturation (2), B (3), and T (4) cell development, Th1 and Th2 responses, infections, angiogenesis, and tumor growth as well as metastasis (5). Furthermore, an increase in the number of chemokine/receptor transgenic and knock-out mice has helped to define the functions of chemokines in vivo. In this review we discuss some of the chemokines' biological effects in vivo and in vitro, described in the last few years, and the implications of these findings when considering chemokine receptors as therapeutic targets.

Biodiversity hotspots for conservation priorities

Norman Myers, Russell A. Mittermeier, Cristina G. Mittermeier, Gustavo A. B. da Fonseca, Jennifer Kent

International Journal of Nursing Studies

This is a methodological study in which a case report is used to retrospectively analyse the link between a successful pilot study and stalled main study to identify potential methodological weaknesses in the planning process. The analysis identified unanticipated influences related to hospital processes and discipline boundaries that adversely influenced participant recruitment and retention for a clinical trial. The findings of the study demonstrate that, whilst the pilot is an important step in research planning to confirm the design and operational processes for a study, a thorough analysis of the relevant health service environment is an important additional objective for the pilot study. Author Keywords: Pilot study; Research methodology; Postoperative pain 1.

A Theoretical Extension of the Technology Acceptance Model: Four Longitudinal Field Studies

Viswanath Venkatesh, Fred D. Davis

The present research develops and tests a theoretical extension of the Technology Acceptance Model (TAM) that explains perceived usefulness and usage intentions in terms of social influence and cognitive instrumental processes. The extended model, referred to as TAM2, was tested using longitudinal data collected regarding four different systems at four organizations (N = 156), two involving voluntary usage and two involving mandatory usage. Model constructs were measured at three points in time at each organization: preimplementation, one month postimplementation, and three months postimplementation. The extended model was strongly supported for all four organizations at all three points of measurement, accounting for 40%–60% of the variance in usefulness perceptions and 34%–52% of the variance in usage intentions. Both social influence processes (subjective norm, voluntariness, and image) and cognitive instrumental processes (job relevance, output quality, result demonstrability, and perceived ease of use) significantly influenced user acceptance. These findings advance theory and contribute to the foundation for future research aimed at improving our understanding of user adoption behavior.

Self-determination theory and the facilitation of intrinsic motivation, social development, and well-being.

Richard M. Ryan, Edward L. Deci

Human beings can be proactive and engaged or, alternatively, passive and alienated, largely as a function of the social conditions in which they develop and function. Accordingly, research guided by self-determination theory has focused on the social-contextual conditions that facilitate versus forestall the natural processes of self-motivation and healthy psychological development. Specifically, factors have been examined that enhance versus undermine intrinsic motivation, self-regulation, and well-being. The findings have led to the postulate of three innate psychological needs--competence, autonomy, and relatedness--which when satisfied yield enhanced self-motivation and mental health and when thwarted lead to diminished motivation and well-being. Also considered is the significance of these psychological needs and processes within domains such as health care, education, work, sport, religion, and psychotherapy.

The Hallmarks of Cancer

Douglas Hanahan, Robert A. Weinberg

The Protein Data Bank

Helen M. Berman

The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.

Lecture Notes in Computer Science 1867

JF Baldwin, Trevor Martin, Aimilia Tzanavari

Mixed MNL models for discrete response

Daniel McFadden, Kenneth Train

This paper considers mixed, or random coefficients, multinomial logit (MMNL) models for discrete response, and establishes the following results. Under mild regularity conditions, any discrete choice model derived from random utility maximization has choice probabilities that can be approximated as closely as one pleases by a MMNL model. Practical estimation of a parametric mixing family can be carried out by Maximum Simulated Likelihood Estimation or Method of Simulated Moments, and easily computed instruments are provided that make the latter procedure fairly efficient. The adequacy of a mixing specification can be tested simply as an omitted variable test with appropriately defined artificial variables. An application to a problem of demand for alternative vehicles shows that MMNL provides a flexible and computationally practical approach to discrete response analysis. Copyright © 2000 John Wiley & Sons, Ltd.

Structural Equation Modeling and Regression: Guidelines for Research Practice

David Gefen, Detmar W. Straub, Marie‐Claude Boudreau

The growing interest in Structured Equation Modeling (SEM) techniques and recognition of their importance in IS research raises the need to compare and contrast the different types of SEM techniques so that research designs can be selected appropriately. After assessing the extent to which these techniques are currently being used in IS research, the article presents a running example which analyzes the same dataset via three very different statistical techniques. It then compares two classes of SEM: covariance-based SEM and partial-least-squares-based SEM. Finally, the article discusses linear regression models and suggests guidelines as to when SEM techniques and when regression techniques should be used. The article concludes with heuristics and rule of thumb thresholds to guide practice, and a discussion of the extent to which practice is in accord with these guidelines.

Modeling Survival Data: Extending the Cox Model

Terry M. Therneau, Patricia M. Grambsch

Longman Grammar of Spoken and Written English

Kathleen M. Broussard, Douglas Biber, Stig Johansson, Geoffrey Leech, Susan Conrad, Edward Finegan

Introduction Since its publication in 1985, the outstanding 1,800-page Comprehensive Grammar of the English Language, by Randolph Quirk, Sidney Greenbaum, Geoffrey Leech, and Jan Svartvik, has been the definitive description of the grammar of English and an in-. dispensable reference for any research in the analysis or generation of English that attempts serious coverage of the syntactic phenomena of the language. The new Longman Grammar of Spoken and Written English, by Douglas Biber, Stig Johansson, Geoffrey Leech, Susan Conrad, and Edward Finegan, is an important complement to the earlier work, extending and sometimes revising the descriptions of Quirk et al., by means of an extensive corpus analysis by the five authors and their research assistants. Now, the bookshelf of any researcher in English linguistics is incomplete without both volumes. Like Quirk et al. (hereafter CGEL), Biber and his colleagues attempt a detailed description of all the syntactic phenomena of English. But

Four Horizons for Enhancing the Performance of Parallel Simulations Based on Partial Differential Equations

David E. Keyes

The Mathematics of Infectious Diseases

Herbert W. Hethcote

Abstract. Many models for the spread of infectious diseases in populations have been analyzed mathematically and applied to specific diseases. Threshold theorems involving the basic reproduction number R0, the contact number σ, and the replacement number R are reviewed for the classic SIR epidemic and endemic models. Similar results with new expressions for R0 are obtained for MSEIR and SEIR endemic models with either continuous age or age groups. Values of R0 and σ are estimated for various diseases including measles in Niger and pertussis in the United States. Previous models with age structure, heterogeneity, and spatial structure are surveyed.

From molecular to modular cell biology

Leland H. Hartwell, J. J. Hopfield, Stanislas Leibler, Andrew W. Murray

Out-of-plane measurements of the fifth response function of the exclusive electronuclear response

S. Dolfini, Ricardo Alarcón, H. Arenhövel, R. Beck, A. M. Bernstein, W. Bertozzi, W. Boeglin, S. Boffi, J. R. Comfort, D. Da…

The first measurements of ${f}_{\mathrm{LT}}^{\ensuremath{'}},$ known as the fifth response function, have been made for the ${}^{2}\mathrm{H}(\stackrel{\ensuremath{\rightarrow}}{e}{,e}^{\ensuremath{'}}p)$ and ${}^{12}\mathrm{C}(\stackrel{\ensuremath{\rightarrow}}{e}{,e}^{\ensuremath{'}}p)$ reactions. This response is directly related to the imaginary part of the interference between the transverse and longitudinal nuclear electromagnetic currents. Its observation requires longitudinally polarized electron beams and out-of-plane detection, the latter made possible by the newly developed out-of-plane spectrometer system. The initial measurements were made by using a 560-MeV polarized electron beam and quasielastic kinematics at ${Q}^{2}=3.3 {\mathrm{fm}}^{\ensuremath{-}2}.$ The development of the methodology for out-of-plane physics, and the analysis of the data from the initial experiments are described in detail. The measured fifth response and the related asymmetry in the coincidence cross section are in agreement, albeit with large statistical errors, with the theoretical predictions. Future extensions of the out-of-plane program are also discussed.

Methods of Mathematical Physics

Harold Jeffreys, Bertha Jeffreys

This well-known text and reference contains an account of those parts of mathematics that are most frequently needed in physics. As a working rule, it includes methods which have applications in at least two branches of physics. The authors have aimed at a high standard of rigour and have not accepted the often-quoted opinion that 'any argument is good enough if it is intended to be used by scientists'. At the same time, they have not attempted to achieve greater generality than is required for the physical applications: this often leads to considerable simplification of the mathematics. Particular attention is also paid to the conditions under which theorems hold. Examples of the practical use of the methods developed are given in the text: these are taken from a wide range of physics, including dynamics, hydrodynamics, elasticity, electromagnetism, heat conduction, wave motion and quantum theory. Exercises accompany each chapter.

Statistical Learning Theory

Yuhai Wu, Vladimir Vapnik

A comprehensive look at learning and generalization theory. The statistical theory of learning and generalization concerns the problem of choosing desired functions on the basis of empirical data. Highly applicable to a variety of computer science and robotics fields, this book offers lucid coverage of the theory as a whole. Presenting a method for determining the necessary and sufficient conditions for consistency of learning process, the author covers function estimates from small data pools, applying these estimations to real-life problems, and much more.

Emergence of Scaling in Random Networks

Albert-Ĺaszló Barabási, Réka Albert

Systems as diverse as genetic networks or the World Wide Web are best described as networks with complex topology. A common property of many large networks is that the vertex connectivities follow a scale-free power-law distribution. This feature was found to be a consequence of two generic mechanisms: (i) networks expand continuously by the addition of new vertices, and (ii) new vertices attach preferentially to sites that are already well connected. A model based on these two ingredients reproduces the observed stationary scale-free distributions, which indicates that the development of large networks is governed by robust self-organizing phenomena that go beyond the particulars of the individual systems.

Advanced inorganic chemistry

For more than a quarter century, Cotton and Wilkinson's Advanced Inorganic Chemistry has been the source that students and professional chemists have turned to for the background needed to understand current research literature in inorganic chemistry and aspects of organometallic chemistry. Like its predecessors, this updated Sixth Edition is organized around the periodic table of elements and provides a systematic treatment of the chemistry of all chemical elements and their compounds. It incorporates important recent developments with an emphasis on advances in the interpretation of structure, bonding, and reactivity.From the reviews of the Fifth Edition:* The first place to go when seeking general information about the chemistry of a particular element, especially when up-to-date, authoritative information is desired. -Journal of the American Chemical Society.* Every student with a serious interest in inorganic chemistry should have [this book]. -Journal of Chemical Education.* A mine of information . . . an invaluable guide. -Nature.* The standard by which all other inorganic chemistry books are judged.-Nouveau Journal de Chimie.* A masterly overview of the chemistry of the elements.-The Times of London Higher Education Supplement.* A bonanza of information on important results and developments which could otherwise easily be overlooked in the general deluge of publications. -Angewandte Chemie.