bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized Quasiparticle Energies in Many-Body Perturbation Theory
Authors: Surján Peter R. , Kőhalmi Dóra , Szabados Ágnes
Published: March 2003

For the calculation of the electron correlation energy, usual Koopmans one-electron energies (used in Møller-Plesset partitioning) are replaced by energy-optimized ones to form the denominators of the many-body perturbation theory. Changing these quasiparticle energies can be interpreted as applying special level shifts to the zero-order Hamiltonian, thus it is related to the problem of partitioning in the perturbation theory. The energy functional chosen to be optimized with respect to the quasiparticle energies is the Rayleigh quotient evaluated with the first-order wavefunction Ansatz, expanded up to the third order. The resulting level shifts preserve size extensivity of the many-body perturbation theory.
Towards Universal R12 Consistent Basis Sets
Authors: Noga Jozef , Valiron Pierre
Published: March 2003

Using H- and H2 as examples, it is demonstrated that parameters of the one-electron basis sets optimized for explicitly correlated R12 calculations are quite different from those developed for conventional calculations that utilize a usual configuration interaction expansion for the wavefunction. Systematic development of universal R12 suited basis sets is suggested, using the even-tempered paradigm. In explicitly correlated calculations, such R12 consistent basis sets should describe the given atom in a variety of bonding situations with a few μEh absolute accuracy.
The Laplace Transform Perturbative Triples Correction Ansatz
Authors: Constans Pere , Scuseria Gustavo E.
Published: March 2003

We describe the implementation of the spin-unrestricted Laplace transform fourth-order perturbative triples correction. A reduction in the computational scaling with respect to canonical implementations is attained without relying on the large molecule asymptote. The intrinsic scaling difficulties that the Laplace equations exhibit upon increasing the size of the basis sets are properly addressed. The method is suited for medium-size molecules.
Similarity-Transformed Hamiltonians by Means of Gaussian-Damped Interelectronic Distances
Authors: Zweistra Henk J. A. , Samson Claire C. M. , Klopper Wim
Published: March 2003

A method is presented to improve the description of electron correlation in configuration interaction (CI) calculations. In this method, the standard CI expansion ψ is multiplied by a correlation function ϕ = exp (F) with F = Σ(from m = 1 to M) cm Σ(for i < j) rij exp(-γmrij2). With this correlation function, the total wavefunction Ψ = ϕψ exhibits the right behavior when two electron coalesce while F vanishes for large interelectronic distances. The correlation function is implemented using the methodology of similarity-transformed Hamiltonians and is applied to two-electron systems. A generalization to many-electron systems is indicated. The new method yields more accurate results than standard CI calculations of the energy and interelectronic distance of the He atom. The H2 molecule was chosen to study the long-range behavior of the correlation function.
Electronic Structure and Bonding Nature of the Ground State Monocarbide Cations, ScC+, TiC+, VC+, and CrC+
Authors: Kerkines Ioannis S. K. , Mavridis Aristides
Published: March 2003

The ground states of the transition-metal diatomic carbide cations, MC+ (M = Sc, Ti, V, and Cr), are studied using multireference configuration interaction (MRCI) methods in conjunction with quantitative basis sets. Full potential energy curves are calculated for all four systems. When 3s23p6 core/valence correlation contributions and scalar relativistic effects are taken into account, our best estimates for the zero-point-corrected dissociation energies of the MC+ series are in good agreement with relevant experimental results. For TiC+, the recent correlation-consistent-type basis sets for Ti of Bauschlicher are also exploited to extract complete basis set limits of selected properties. The ground states of VC+(X 3∆) and CrC+(X 2∆) are reported for the first time in the literature. For CrC+ an interesting competition is revealed between the 2∆ and 4Σ- states; although 4Σ- is formally the ground state at the MRCI level of theory, when core/valence and/or relativistic effects are included, the ground state of CrC+ becomes of 2∆ symmetry, with a calculated energy separation (a 4Σ- ← X 2∆) of 2.3 kcal/mol.
Electronic States of Fe2S-/0/+
Authors: Hübner Olaf , Sauer Joachim
Published: March 2003

The relative energies of a multitude of low-lying electronic states of Fe2S-/0/+ are determined by complete active space self-consistent field (CASSCF) calculations. The numerous states obtained are assigned to spin ladders. For selected states, dynamic correlation has been included by multireference configuration interaction (MRCI) and the structures of some high-spin states have been optimized by CASSCF/MRCI. Comparison is made with structures obtained by density-functional theoretical calculations. The ground states of Fe2S-/0/+ are 10B2, 1A1 and 8A2, respectively, and the total splittings of the lowest-energy spin ladders are about 0.18, 0.07 and 0.13 eV, respectively. The spin ladders of Fe2S qualitatively reflect the picture of Heisenberg spin coupling. While both Fe2S- and Fe2S+ show an Fe-Fe distance of about 270 pm, that of Fe2S is about 100 pm longer. The calculated adiabatic electron affinity of Fe2S is 1.2 eV and the ionization energy 6.6 eV. An interpretation of the observed photoelectron spectrum of Fe2S- is given.
An audit of job application forms in response to adverts in the British Medical Journal
Authors: Taylor F G M , Daniels I R , George C D
Published: March 2003

Objective

The aim of this study was to examine the speed of response of human resources departments to requests for job application forms for posts advertised in the British Medical Journal (BMJ). Of particular interest was the closing date for applications, postage cost, and the period to reply.

Design

Twenty posts were randomly selected and application forms requested by telephone and then 20 by letter on two separate dates from the BMJ Classified (issues of 21 July 2001 and 28 July 2001). During the first week the forms were requested by telephone on receipt of the BMJ (Friday afternoon). During the second week the forms were requested by first class post. All letters were sent out on Saturday morning.

Outcome measures

The date of receipt of the application form/information pack, the cost of postage, and the closing date for application were recorded for each position.

Results

Fifteen forms were received after the telephone application and 18 forms after the letter applications. One trust sent two replies spaced one week apart for the same job and two replies contained job application forms for the wrong job. The response rates to telephone requests varied from four to 10 days and by letter from three to 12 days. The minimum time between the reply being received and the closing date was one day, and the maximum 21 days. The time between the closing date for applications and the start date of the job varied from minus one week (closing date before advertisement) to three months. Thirteen replies gave no indication of the start date of the job. The cost of postage varied from 27p to £1.90. Thirty one trusts used first class postage.

Conclusion

There is very limited scope to return job application forms on time, and significant delays in sending out application forms and information packs compound this problem. It is recommended that trust human resources departments place advertisements early and respond promptly to requests for application forms.
Effects of the civil procedure rules on clinical negligence claims
Authors: Mayberry M K
Published: March 2003

The frequency with which clinicians can expect to face allegations of clinical negligence and court proceedings related to those allegations is likely to increase in coming years. The processes of investigation and defence have been modified by the introduction of the Civil Procedure Rules in 1999. This review outlines these developments and emphasises the need for speedy and comprehensive responses by doctors involved in such procedures.
Brachial plexus injury as an unusual complication of coronary artery bypass graft surgery
Authors: Chong A Y , Clarke C E , Dimitri W R , Lip G Y H
Published: March 2003

Brachial plexus injury is an unusual and under-recognised complication of coronary artery bypass grafting especially when internal mammary artery harvesting takes place. It is believed to be due to sternal retraction resulting in compression of the brachial plexus. Although the majority of cases are transient, there are cases where the injury is permanent and may have severe implications as illustrated in the accompanying case history.
Signals for Sorting of Transmembrane Proteins to Endosomes and Lysosomes
Authors: Bonifacino Juan S. , Traub Linton M.
Published: March 2003

▪ Abstract  Sorting of transmembrane proteins to endosomes and lysosomes is mediated by signals present within the cytosolic domains of the proteins. Most signals consist of short, linear sequences of amino acid residues. Some signals are referred to as tyrosine-based sorting signals and conform to the NPXY or YXXØ consensus motifs. Other signals known as dileucine-based signals fit [DE]XXXL[LI] or DXXLL consensus motifs. All of these signals are recognized by components of protein coats peripherally associated with the cytosolic face of membranes. YXXØ and [DE]XXXL[LI] signals are recognized with characteristic fine specificity by the adaptor protein (AP) complexes AP-1, AP-2, AP-3, and AP-4, whereas DXXLL signals are recognized by another family of adaptors known as GGAs. Several proteins, including clathrin, AP-2, and Dab2, have been proposed to function as recognition proteins for NPXY signals. YXXØ and DXXLL signals bind in an extended conformation to the μ2 subunit of AP-2 and the VHS domain of the GGAs, respectively. Phosphorylation events regulate signal recognition. In addition to peptide motifs, ubiquitination of cytosolic lysine residues also serves as a signal for sorting at various stages of the endosomal-lysosomal system. Conjugated ubiquitin is recognized by UIM, UBA, or UBC domains present within many components of the internalization and lysosomal targeting machinery. This complex array of signals and recognition proteins ensures the dynamic but accurate distribution of transmembrane proteins to different compartments of the endosomal-lysosomal system.
Genomic Organization of the MammalianMhc
Authors: Kumánovics Attila , Takada Toyoyuki , Lindahl Kirsten Fischer
Published: March 2003

The Human Genome Project transformed the quest of more than 50 years to understand the major histocompatibility complex (Mhc). The sequence of the Mhc from human and mouse, together with a large amount of sequence and mapping information from several other species, allows us to draw general conclusions about the organization and origin of this crucial part of the immune system. The Mhc is a mosaic of stretches formed by conserved and nonconserved genes. Surprisingly, of the ∼3.6-Mb Mhc, the stretches that encode the class I and class II genes, which epitomize the Mhc, are the least conserved part, whereas the ∼1.7-Mb stretches that encode at least 115 other genes are highly conserved. We summarize the available data to answer the questions (a) What is the Mhc? and (b) How can we define it in a general, not species-specific, way? Knowing what is essential and what is incidental helps us understand the fundamentals of the Mhc, and defining the species differences makes the model organisms more useful.
The Meandering 45-Year Odyssey of a Clinical Immunologist
Authors: Waldmann Thomas A.
Published: March 2003

My work on basic and clinical immunology has focused on the regulation of the human immune response and how its dysregulation can lead to immunodeficiency, autoimmune, and malignant disorders. The early focus in our laboratory was on pathogenic mechanisms underlying hypogammaglobulinemia. Our demonstration of active suppression by human suppressor T cells changed thinking about the pathogenesis of certain immunodeficiency disorders. Recently we have focused on the cytokines interleukin-2 (IL-2) and IL-15, which have competitive functions in adaptive immune responses. IL-2 is necessary to destroy self-reactive lymphocytes and thus favors peripheral tolerance to self-antigens, whereas IL-15 favors the persistence of lymphocytes involved in the memory and effector responses to invading pathogens but risks the development of inflammatory autoimmune diseases. Our murine anti-Tac monoclonal antibody exploits these differences, as does a humanized form (daclizumab) now approved for the prevention of renal allograft rejection. New forms of therapy directed at IL-2 and IL-15 receptors may be effective against certain neoplastic diseases and autoimmune disorders and in the prevention of allograft rejection.
Molecular Mechanisms RegulatinG Th1 Immune Responses
Authors: Szabo Susanne J. , Sullivan Brandon M. , Peng Stanford L. , Glimcher Laurie H.
Published: March 2003

The T helper lymphocyte is responsible for orchestrating the appropriate immune response to a wide variety of pathogens. The recognition of the polarized T helper cell subsets Th1 and Th2 has led to an understanding of the role of these cells in coordinating a variety of immune responses, both in responses to pathogens and in autoimmune and allergic disease. Here, we discuss the mechanisms that control lineage commitment to the Th1 phenotype. What has recently emerged is a rich understanding of the cytokines, receptors, signal transduction pathways, and transcription factors involved in Th1 differentiation. Although the picture is still incomplete, the basic pathways leading to Th1 differentiation can now be understood in in vitro and a number of infection and disease models.
CD45: A Critical Regulator of Signaling Thresholds in Immune Cells
Authors: Hermiston Michelle L. , Xu Zheng , Weiss Arthur
Published: March 2003

▪ Abstract  Regulation of tyrosine phosphorylation is a critical control point for integration of environmental signals into cellular responses. This regulation is mediated by the reciprocal actions of protein tyrosine kinases and phosphatases. CD45, the first and prototypic receptor-like protein tyrosine phosphatase, is expressed on all nucleated hematopoietic cells and plays a central role in this process. Studies of CD45 mutant cell lines, CD45-deficient mice, and CD45-deficient humans initially demonstrated the essential role of CD45 in antigen receptor signal transduction and lymphocyte development. It is now known that CD45 also modulates signals emanating from integrin and cytokine receptors. Recent work has focused on regulation of CD45 expression and alternative splicing, isoform-specific differences in signal transduction, and regulation of phosphatase activity. From these studies, a model is emerging in which CD45 affects cellular responses by controlling the relative threshold of sensitivity to external stimuli. Perturbation of this function may contribute to autoimmunity, immunodeficiency, and malignancy. Moreover, recent advances suggest that modulation of CD45 function can have therapeutic benefit in many disease states.
Collectins and Ficolins: Humoral Lectins of the Innate Immune Defense
Authors: Holmskov Uffe , Thiel Steffen , Jensenius Jens C.
Published: March 2003

Collectins and ficolins, present in plasma and on mucosal surfaces, are humoral molecules of the innate immune systems, which recognize pathogen-associated molecular patterns. The human collectins, mannan-binding lectin (MBL) and surfactant protein A and D (SP-A and SP-D), are oligomeric proteins composed of carbohydrate-recognition domains (CRDs) attached to collagenous regions and are thus structurally similar to the ficolins, L-ficolin, M-ficolin, and H-ficolin. However, they make use of different CRD structures: C-type lectin domains for the collectins and fibrinogen-like domains for the ficolins. Upon recognition of the infectious agent, MBL and the ficolins initiate the lectin pathway of complement activation through attached serine proteases (MASPs), whereas SP-A and SP-D rely on other effector mechanisms: direct opsonization, neutralization, and agglutination. This limits the infection and concurrently orchestrates the subsequent adaptive immune response. Deficiencies of the proteins may predispose to infections or other complications, e.g., reperfusion injuries or autoimmune diseases. Structure, function, clinical implications, and phylogeny are reviewed.
IgA Fc Receptors
Authors: Monteiro Renato C. , van de Winkel Jan G. J.
Published: March 2003

The IgA receptor family comprises a number of surface receptors including the polymeric Ig receptor involved in epithelial transport of IgA/IgM, the myeloid specific IgA Fc receptor (FcαRI or CD89), the Fcα/μR, and at least two alternative IgA receptors. These are the asialoglycoprotein receptor and the transferrin receptor, which have been implicated in IgA catabolism, and tissue IgA deposition. In this reviewwe focus on the biology of FcαRI (CD89). FcαRI is expressed on neutrophils, eosinophils, monocytes/macrophages, dendritic cells, and Kupffer cells. This receptor represents a heterogeneously glycosylated transmembrane protein that binds both IgA subclasses with low affinity. A single gene encoding FcαRI has been isolated, which is located within the leukocyte receptor cluster on chromosome 19. The FcαRI α chain lacks canonical signal transduction domains but can associate with the FcR γ-chain that bears an activation motif (ITAM) in the cytoplasmic domain, allowing activatory functions. FcαRI expressed alone mediates endocytosis and recyling of IgA. No FcαRI homologue has been defined in the mouse, and progress in defining the in vivo role of FcαRI has been made using human FcαRI transgenic (Tg) mice. FcαRI-Tg mice demonstrated FcαRI expression on Kupffer cells and so defined a key role for the receptor in mucosal defense. The receptor functions as a second line of antibacterial defense involving serum IgA rather than secretory IgA. Studies in FcαRI-Tg mice, furthermore, defined an essential role for soluble FcαRI in the development of IgA nephropathy by formation of circulating IgA-FcαRI complexes. Finally, recent work points out a role for human IgA in treatment of infectious and neoplastic diseases.
B Cell Chronic Lymphocytic Leukemia: Lessons Learned from Studies of the B Cell Antigen Receptor
Authors: Chiorazzi Nicholas , Ferrarini Manlio
Published: March 2003

B cell chronic lymphocytic leukemia (B-CLL) is an accumulative disease of slowly proliferating CD5+B lymphocytes that develops in the aging population. Whereas some patients with B-CLL have an indolent course and die after many years from unrelated causes, others progress very rapidly and succumb within a few years from this currently incurable leukemia. Over the past decade studies of the structure and function of the B cell antigen receptor (BCR) used by these leukemic cells have helped redefine the nature of this disease. In this review we summarize and reinterpret several aspects of these BCR-related studies and how they might relate to the disease. In particular, we address the ability of antigens to select out and drive B cell clones from the normal state to overt leukemic cells by binding to BCRs that are relatively unique and characteristic of B-CLL cells. The differential capacity of some B-CLL cases to continue to transduce signals through the BCR during the leukemic phase and the consequences for the in vivo biology of the leukemic clone is also considered. Finally, we discuss current and emerging views of the cellular origin of B-CLL cells and the differentiation pathways down which we believe these cells progress.
Location is Everything: Lipid Rafts and Immune Cell Signaling
Authors: Dykstra Michelle , Cherukuri Anu , Sohn Hae Won , Tzeng Shiang-Jong , Pierce Susan K.
Published: March 2003

The cells of both the adaptive and innate immune systems express a dizzying array of receptors that transduce and integrate an enormous amount of information about the environment that allows the cells to mount effective immune responses. Over the past several years, significant advances have been made in elucidating the molecular details of signal cascades initiated by the engagement of immune cell receptors by their ligands. Recent evidence indicates that immune receptors and components of their signaling cascades are spatially organized and that this spatial organization plays a central role in the initiation and regulation of signaling. A key organizing element for signaling receptors appears to be cholesterol- and sphingolipid-rich plasma membrane microdomains termed lipid rafts. Research into the molecular basis of the spatial segregation and organization of signaling receptors provided by rafts is adding fundamentally to our understanding of the initiation and prolongation of signals in the immune system.
Control of Apoptosis in the Immune System: Bcl-2, BH3-Only Proteins and More
Authors: Marsden Vanessa S. , Strasser Andreas
Published: March 2003

Apoptotic cell death plays a critical role in the development and functioning of the immune system. During differentiation, apoptosis weeds out lymphocytes lacking useful antigen receptors and those expressing dangerous ones. Lymphocyte death is also involved in limiting the magnitude and duration of immune responses to infection. In this review, we describe the role of the Bcl-2 protein family, and to a lesser extent that of death receptors (members of the tumor necrosis factor receptor family with a death domain), in the control of lymphoid and myeloid cell survival. We also consider the pathogenic consequences of failure of apoptosis in the immune system.
Molecular Interactions Mediating T Cell Antigen Recognition
Authors: Merwe P. Anton van der , Davis Simon J.
Published: March 2003

▪ Abstract  Over the past decade, key protein interactions contributing to T cell antigen recognition have been characterized in molecular detail. These have included interactions involving the T cell antigen receptor (TCR) itself, its coreceptors CD4 and CD8, the accessory molecule CD2, and the costimulatory receptors CD28 and CTLA-4. A clear view is emerging of how these molecules interact with their ligands at the cell-cell interface. Structural and binding studies have confirmed that the proteins span small but comparable distances and that, overall, they interact very weakly. However, there have been important surprises as well: that TCR interactions with peptide-MHC are topologically constrained and characterized by considerable conformational flexibility at the binding interface; that coreceptors engage peptide-MHC with extraordinarily fast kinetics and at angles apparently precluding direct interactions with the TCR bound to the same peptide-MHC; that the structural mechanisms allowing recognition by costimulatory and accessory molecules to be weak and yet specific are very heterogeneous; and that because of differences in both binding affinity and stoichiometry, there is enormous variation in the stability of the various costimulatory receptor/ligand complexes. These studies provide the necessary framework for exploring how these molecular interactions initiate T cell activation.
Tolerogenic Dendritic Cells
Authors: Steinman Ralph M. , Hawiger Daniel , Nussenzweig Michel C.
Published: March 2003

▪ Abstract  Dendritic cells (DCs) have several functions in innate and adaptive immunity. In addition, there is increasing evidence that DCs in situ induce antigen-specific unresponsiveness or tolerance in central lymphoid organs and in the periphery. In the thymus DCs generate tolerance by deleting self-reactive T cells. In peripheral lymphoid organs DCs also induce tolerance to antigens captured by receptors that mediate efficient uptake of proteins and dying cells. Uptake by these receptors leads to the constitutive presentation of antigens on major histocompatibility complex (MHC) class I and II products. In the steady state the targeting of DC antigen capture receptors with low doses of antigens leads to deletion of the corresponding T cells and unresponsiveness to antigenic rechallenge with strong adjuvants. In contrast, if a stimulus for DC maturation is coadministered with the antigen, the mice develop immunity, including interferon-γ-secreting effector T cells and memory T cells. There is also new evidence that DCs can contribute to the expansion and differentiation of T cells that regulate or suppress other immune T cells. One possibility is that distinct developmental stages and subsets of DCs and T cells can account for the different pathways to peripheral tolerance, such as deletion or suppression. We suggest that several clinical situations, including autoimmunity and certain infectious diseases, can be influenced by the antigen-specific tolerogenic role of DCs.
On Natural and Artificial Vaccinations
Authors: Zinkernagel Rolf M.
Published: March 2003

This review summarizes the general parameters of cell- and antibody-mediated immune protection and the basic mechanisms responsible for what we call immunological memory. From this basis, the various successes and difficulties of vaccines are evaluated with respect to the role of antigen in maintaining protective immunity. Based on the fact that in humans during the first 12–48 months maternal antibodies from milk and serum protect against classical acute childhood and other infections, the concept is developed that maternal antibodies attenuate most infections of babies and infants and turn them into effective vaccines. If this “natural vaccination” under passive protective conditions does not occur, acute childhood diseases may be severe, unless infants are actively vaccinated with conventional vaccines early enough, i.e., in synchronization with the immune system's maturation. Although vaccines are available against the classical childhood diseases, they are not available for many seemingly milder childhood infections such as gastrointestinal and respiratory infections; these may eventually trigger immunopathological diseases. These changing balances between humans and infections caused by changes in nursing habits but also in hygiene levels may well be involved in changing disease patterns including increased frequencies of certain autoimmune and degenerative diseases.
Poxviruses and Immune Evasion
Authors: Seet Bruce T. , Johnston J.B. , Brunetti Craig R. , Barrett John W. , Everett Helen , Cameron Cheryl , Sypula Joanna , Nazarian Steven H. , Lucas Alexandra , McFadden Grant
Published: March 2003

Large DNA viruses defend against hostile assault executed by the host immune system by producing an array of gene products that systematically sabotage key components of the inflammatory response. Poxviruses target many of the primary mediators of innate immunity including interferons, tumor necrosis factors, interleukins, complement, and chemokines. Poxviruses also manipulate a variety of intracellular signal transduction pathways such as the apoptotic response. Many of the poxvirus genes that disrupt these pathways have been hijacked directly from the host immune system, while others have demonstrated no clear resemblance to any known host genes. Nonetheless, the immunological targets and the diversity of strategies used by poxviruses to disrupt these host pathways have provided important insights into diverse aspects of immunology, virology, and inflammation. Furthermore, because of their anti-inflammatory nature, many of these poxvirus proteins hold promise as potential therapeutic agents for acute or chronic inflammatory conditions.
T Cell Dynamics in HIV-1 Infection
Authors: Douek Daniel C. , Picker Louis J. , Koup Richard A.
Published: March 2003

▪ Abstract  In the absence of antiretroviral treatment, HIV-1 establishes a chronic, progressive infection of the human immune system that invariably, over the course of years, leads to its destruction and fatal immunodeficiency. Paradoxically, while viral replication is extensive throughout the course of infection, deterioration of conventional measures of immunity is slow, including the characteristic loss of CD4+T cells that is thought to play a key role in the development of immunodeficiency. This conundrum suggests that CD4+T cell–directed viral cytopathicity alone cannot explain the course of disease. Indeed, recent advances now indicate that HIV-1 pathogenesis is likely to result from a complex interplay between the virus and the immune system, particularly the mechanisms responsible for T cell homeostasis and regeneration. We review these data and present a model of HIV-1 pathogenesis in which the protracted loss of CD4+T cells results from early viral destruction of selected memory T cell populations, followed by a combination of profound increases in overall memory T cell turnover, damage to the thymus and other lymphoid tissues, and physiological limitations in peripheral CD4+T cell renewal.
The Regulatory Role of Vα14 NKT Cells in Innate and Acquired Immune Response
Authors: Taniguchi Masaru , Harada Michishige , Kojo Satoshi , Nakayama Toshinori , Wakao Hiroshi
Published: March 2003

A novel lymphocyte lineage, Vα14 natural killer T (NKT) cells, is now well established as distinct from conventional αβ T cells. Vα14 NKT cells express a single invariant Vα14 antigen receptor that is essential for their development. Successful identification of a specific ligand, α-galactosylceramide(α-GalCer), and the establishment of gene-manipulated mice with selective loss of Vα14 NKT cells helped elucidate the remarkable functional diversity of Vα14 NKT cells in various immune responses such as host defense by mediating anti-nonself innate immune reaction, homeostatic regulation of anti-self responses, and antitumor immunity.
The Biology of IgE and the Basis of Allergic Disease
Authors: Gould Hannah J. , Sutton Brian J. , Beavil Andrew J. , Beavil Rebecca L. , McCloskey Natalie , Coker Heather A. , Fear David , Smurthwaite Lyn
Published: March 2003

Allergic individuals exposed to minute quantities of allergen experience an immediate response. Immediate hypersensitivity reflects the permanent sensitization of mucosal mast cells by allergen-specific IgE antibodies bound to their high-affinity receptors (FcεRI). A combination of factors contributes to such long-lasting sensitization of the mast cells. They include the homing of mast cells to mucosal tissues, the local synthesis of IgE, the induction of FcεRI expression on mast cells by IgE, the consequent downregulation of FcγR (through an insufficiency of the common γ-chains), and the exceptionally slow dissociation of IgE from FcεRI. To understand the mechanism of the immediate hypersensitivity phenomenon, we need explanations of why IgE antibodies are synthesized in preference to IgG in mucosal tissues and why the IgE is so tenaciously retained on mast cell–surface receptors. There is now compelling evidence that the microenvironment of mucosal tissues of allergic disease favors class switching to IgE; and the exceptionally high affinity of IgE for FcεRI can now be interpreted in terms of the recently determined crystal structures of IgE-FcεRI and IgG-FcγR complexes. The rate of local IgE synthesis can easily compensate for the rate of the antibody dissociation from its receptors on mucosal mast cells. Effective mechanisms ensure that allergic reactions are confined to mucosal tissues, thereby minimizing the risk of systemic anaphylaxis.
T Cell Anergy
Authors: Schwartz Ronald H.
Published: March 2003

T cell anergy is a tolerance mechanism in which the lymphocyte is intrinsically functionally inactivated following an antigen encounter, but remains alive for an extended period of time in a hyporesponsive state. Models of T cell anergy affecting both CD4+and CD8+cells fall into two broad categories. One, clonal anergy, is principally a growth arrest state, whereas the other, adaptive tolerance or in vivo anergy, represents a more generalized inhibition of proliferation and effector functions. The former arises from incomplete T cell activation, is mostly observed in previously activated T cells, is maintained by a block in the Ras/MAP kinase pathway, can be reversed by IL-2 or anti-OX40 signaling, and usually does not result in the inhibition of effector functions. The latter is most often initiated in naïve T cells in vivo by stimulation in an environment deficient in costimulation or high in coinhibition. Adaptive tolerance can be induced in the thymus or in the periphery. The cells proliferate and differentiate to varying degrees and then downregulate both functions in the face of persistent antigen. The state involves an early block in tyrosine kinase activation, which predominantly inhibits calcium mobilization, and an independent mechanism that blocks signaling through the IL-2 receptor. Adaptive tolerance reverses in the absence of antigen. Aspects of both of the anergic states are found in regulatory T cells, possibly preventing them from dominating initial immune responses to foreign antigens and shutting down such responses prematurely.
CD8 T Cell Responses to Infectious Pathogens
Authors: Wong Phillip , Pamer Eric G.
Published: March 2003

CD8 T cells respond to viral infections but also participate in defense against bacterial and protozoal infections. In the last few years, as new methods to accurately quantify and characterize pathogen-specific CD8 T cells have become available, our understanding of in vivo T cell responses has increased dramatically. Pathogen-specific T cells, once thought to be quite rare following infection, are now known to be present at very high frequencies, particularly in peripheral, nonlymphoid tissues. With the ability to visualize in vivo CD8 T cell responses has come the recognition that T cell expansion is programmed and, to a great extent, independent of antigen concentrations. Comparison of CD8 T cell responses to different pathogens also highlights the intricate relationship between microbially induced innate inflammatory responses and the kinetics, magnitude, and character of long-term T cell responses. This review describes recent progress in some of the major murine models of CD8 T cell–mediated immunity to viral, bacterial, and protozoal infection.
Toll-Like Receptors
Authors: Takeda Kiyoshi , Kaisho Tsuneyasu , Akira Shizuo
Published: March 2003

The innate immune system in drosophila and mammals senses the invasion of microorganisms using the family of Toll receptors, stimulation of which initiates a range of host defense mechanisms. In drosophila antimicrobial responses rely on two signaling pathways: the Toll pathway and the IMD pathway. In mammals there are at least 10 members of the Toll-like receptor (TLR) family that recognize specific components conserved among microorganisms. Activation of the TLRs leads not only to the induction of inflammatory responses but also to the development of antigen-specific adaptive immunity. The TLR-induced inflammatory response is dependent on a common signaling pathway that is mediated by the adaptor molecule MyD88. However, there is evidence for additional pathways that mediate TLR ligand-specific biological responses.
Does the Immune System See Tumors as Foreign or Self?
Authors: Pardoll Drew
Published: March 2003

Given the vast number of genetic and epigenetic changes associated with carcinogenesis, it is clear that tumors express many neoantigens. A central question in cancer immunology is whether recognition of tumor antigens by the immune system leads to activation (i.e., surveillance) or tolerance. Paradoxically, while strong evidence exists that specific immune surveillance systems operate at early stages of tumorigenesis, established tumors primarily induce immune tolerance. A unifying hypothesis posits that the fundamental processes of cancer progression, namely tissue invasion and metastasis, are inherently proinflammatory and thus activating for innate and adaptive antitumor immunity. To elude immune surveillance, tumors must develop mechanisms that block the elaboration and sensing of proinflammatory danger signals, thereby shifting the balance from activation to tolerance induction. Elucidation of these mechanisms provides new strategies for cancer immunotherapy.
Regulatory Mechanisms that Determine the Development and Function of Plasma Cells
Authors: Calame Kathryn L. , Lin Kuo-I , Tunyaplin Chainarong
Published: March 2003

Plasma cells are terminally differentiated final effectors of the humoral immune response. Plasma cells that result from antigen activation of B-1 and marginal zone B cells provide the first, rapid response to antigen. Plasma cells that develop after a germinal center reaction provide higher-affinity antibody and often survive many months in the bone marrow. Transcription factors Bcl-6 and Pax5, which are required for germinal center B cells, block plasmacytic differentiation and repress Blimp-1 and XBP-1, respectively. When Bcl-6-dependent repression of Blimp-1 is relieved, Blimp-1 ensures that plasmacytic development is irreversible by repressing BCL-6 and PAX5. In plasma cells, Blimp-1, XBP-1, IRF4, and other regulators cause cessation of cell cycle, decrease signaling from the B cell receptor and communication with T cells, inhibit isotype switching and somatic hypermutation, downregulate CXCR5, and induce copious immunoglobulin synthesis and secretion. Thus, commitment to plasmacytic differentiation involves inhibition of activities associated with earlier B cell developmental stages as well as expression of the plasma cell phenotype.
IL-13 Effector Functions
Authors: Wynn Thomas A.
Published: March 2003

IL-13 was first recognized for its effects on B cells and monocytes, where it upregulated class II expression, promoted IgE class switching and inhibited inflammatory cytokine production. It was also thought to be functionally redundant with IL-4. However, studies conducted with knockout mice, neutralizing antibodies, and novel antagonists demonstrate that IL-13 possesses several unique effector functions that distinguish it from IL-4. Resistance to most gastrointestinal nematodes is mediated by type-2 cytokine responses, in which IL-13 plays a dominant role. By regulating cell-mediated immunity, IL-13 modulates resistance to intracellular organisms including Leishmania major, Leishmania mexicana, and Listeria monocytogenes. In the lung, IL-13 is the central mediator of allergic asthma, where it regulates eosinophilic inflammation, mucus secretion, and airway hyperresponsiveness. Manipulation of IL-13 effector function may also prove useful in the treatment of some cancers like B-cell chronic lymphocytic leukemia and Hodgkin's disease, where IL-13 modulates apoptosis or tumor cell growth. IL-13 can also inhibit tumor immunosurveillance. As such, inhibitors of IL-13 might be effective as cancer immunotherapeutics by boosting type-1-associated anti-tumor defenses. Finally, IL-13 was revealed as a potent mediator of tissue fibrosis in both schistosomiasis and asthma, which indicates that it is a key regulator of the extracellular matrix. The mechanisms that regulate IL-13 production and/or function have also been investigated, and IL-4, IL-12, IL-18, IFN-γ, IL-10, TGF-β, TNF-α, and the IL-4/IL-13 receptor complex play important roles. This review highlights the effector functions of IL-13 and describes multiple pathways for modulating its activity in vivo.
BAFF and APRIL: A Tutorial on B Cell Survival
Authors: Mackay Fabienne , Schneider Pascal , Rennert Paul , Browning Jeffrey
Published: March 2003

BAFF, a member of the TNF family, is a fundamental survival factor for transitional and mature B cells. BAFF overexpression leads to an expanded B cell compartment and autoimmunity in mice, and elevated amounts of BAFF can be found in the serum of autoimmune patients. APRIL is a related factor that shares receptors with BAFF yet appears to play a different biological role. The BAFF system provides not only potential insight into the development of autoreactive B cells but a relatively simple paradigm to begin considering the balancing act between survival, growth, and death that affects all cells.
TRADE, FOREIGNINVESTMENT, ANDSECURITY
Authors: Rosecrance Richard , Thompson Peter
Published: March 2003

▪ Abstract  Trade interdependence does not always reduce hostility between states. It depends on whether the trade represents vulnerability or sensitivity interdependence. Portfolio investment also does not represent a tie that binds politically. Even more important, foreign direct investment (FDI) represents a link that is costly (and time-consuming) to break. Thus, FDI links between countries are more likely to reduce conflict than trading links. Evidence shows that symmetrical FDI is the most stable guarantor of low conflict between countries. One factor generating conflict may be that scarce factors of production are in political command. Abundant factors, now more generally in power among developed states, may be partly responsible for the diminishment of conflict among these states in recent years.
WHATROLEDOESPREJUDICEPLAY INETHNICCONFLICT?
Authors: Green Donald P. , Seher Rachel L.
Published: March 2003

▪ Abstract  The extensive literatures on prejudice and ethnic conflict exist largely in isolation from one another. This essay attempts to bridge the gap between the social-psychological study of prejudice and macropolitical explanations of ethnic conflict. We argue that social-psychological inquiry could be strengthened by cross-national field research. Macro-level investigation of ethnic conflict would profit from more systematic research design, particularly where authors seek to establish the influence of micro-level mechanisms, such as persuasion by the mass media.
X-ray powder diffraction data for In3.85Zr2.80Sn0.35O12
Authors: Koster Herman
Published: March 2003

X-ray powder diffraction data for In3.85Zr2.80Sn0.35O12 are reported. The powders were prepared using a wet-chemical precipitation method. The XRD data could be fitted with a rhombohedral unit cell in space group R3 (No. 148). The Rietveld refined unit cell parameters are a=0.951 49(2) nm and c=0.889 51(2)nm in a hexagonal setting with Z=3 and Dx=6.69(1)g/cm3.
Update in a Rietveld analysis program for x-ray powder spectro-diffractometry
Authors: Xiao Yanan , Izumi Fujio , Graber Timothy , Viccaro P. James , Wittmer Dale E.
Published: March 2003

A computer program for refining anomalous scattering factors using x-ray powder diffraction data was revised on the basis of the latest version of a versatile pattern-fitting system, RIETAN-2000. The effectiveness of the resulting program was confirmed by applying it to simulated and measured powder-diffraction patterns of Mn3O4 taken at a synchrotron light source.
Structural investigations of UTeO4
Authors: Tripathi S. N. , Namboodiri P. N.
Published: March 2003

Our X-ray powder diffraction data determine that UTeO4 has an orthorhombic unit cell with parameters: a=10.115±0.003 Å, b=10.706±0.002 Å, c=7.833±0.002 Å, and v=848±0.40 (Å)3, i.e., the cell volume twice as large as that of UTeO5. IR spectral studies show that UTeO4 and UTeO5 have almost an identical molecular symmetry. In UTeO4, the effective environment of U and Te remains nearly the same as in UTeO5 and the UO2 group is noncentrosymmetric and nonlinear with little or no interaction with equatorial oxygen. Frequencies of the characteristic stretching bands of UTeO4 are (cm−1): νas (O=U=O)=945, νs (O=U=O)=880, νs (Te–O)eq=818, νas (Te–O)eq=749, νas (Te–O)ax=649, νs (Te–O)ax=561.
Rietveld refinement X-ray powder data of Pr0.7Ba0.3MnO3
Authors: Ellouze M. , Boujelben W. , Fuess H.
Published: March 2003

Powder X-ray diffraction (XRD) data were collected for Pr0.7Ba0.3MnO3. This sample was prepared using the conventional solid state reaction by mixing Pr6O11, Mn2O3, and BaCO3 up to 99.9% purity at 1400 °C in air for 60 h. XRD analysis using the Rietveld method was carried out and it was found that this manganite sample has orthorhombic symmetry with Pnma space group. The lattice parameters are found to be a=5.4900 Å, b=7.7578 Å, and c=5.5227 Å.
X-ray powder diffraction analysis of 2-exo-(β-pyridyl)-6-exo-phenyl-7-oxa-1-azabicyclo[2.2.1]heptane
Authors: Poveda J. C. , Henao J. A. , Pinilla J. A. , Kouznetsov V. V. , Ochoa C.
Published: March 2003

The X-ray powder diffraction pattern for a bridgehead heterocyclic system was determined. 2-exo-(β-pyridyl)-6-exo-phenyl-7-oxa-1-azabicyclo[2.2.1]heptane, C16H16N2O, is triclinic with refined unit cell parameters a=1.1012(2), b=1.3950(2), c=1.0074(3) nm, α=111.09(2)°, β=104.97(2)°, γ=77.38(2)°, V=1.3813(3) nm3, Z=4, and Dx=1.212 g/cm3 with space group P-1 (No. 2).
Synthesis and crystallographic data of a new copper phosphate CuPO4H⋅0.5H2O
Authors: Sierra Germa´n Alberto , Isaza Adriana Echavarria , Palacio Luz Amparo , Saldarriaga Carlos
Published: March 2003

A new copper phosphate, CuPO4H⋅0.5H2O, was synthesized using a low temperature hydrothermal method and characterized by powder X-ray diffraction, thermogravimetric analysis, and chemical analysis. The material is monoclinic, space group P21/c, with a=10.6524(2), b=8.4730(2), c=9.2204(2), β=92.43(0), and V=831.47 Å3.
A versatile and inexpensive XRD specimen holder for highly radioactive or hazardous specimens
Authors: Strachan D. M. , Schaef H. T. , Schweiger M. J. , Simmons K. L. , Woodcock L. J. , Krouse M. K.
Published: March 2003

Two XRD specimen holders we designed for use with highly radioactive specimens are described. An injection mold was fabricated to allow inexpensive production of one of the holders. These holders are suitable for single-time use. The ease of use and disposable nature of this holder resulted in a dramatic reduction in personnel exposure and an uncontaminated diffraction unit. A second holder, based on the design of the first, is used to obtain XRD patterns from powders where preferred orientation is an issue and from clays. Both holders result in negligible background, since the specimen is essentially levitated in the X-ray beam. This is a benefit over other methods, such as collodion, that introduce significant background to the XRD pattern.
Polymorphism of tricalcium silicate in Portland cement: A fast visual identification of structure and superstructure
Authors: Courtial M. , de Noirfontaine M.-N. , Dunstetter F. , Gasecki G. , Signes-Frehel M.
Published: March 2003

So-called alite is a solid solution of tricalcium silicate Ca3SiO5 with a few percent of impurities. It constitutes the major phase of anhydrous Portland cement. In industrial compounds, alite crystallizes into two monoclinic forms designated M1 and M3. The possibility of correlation between the crystallographic structure of the clinker and its reactivity is still an open question. The answer of such a question involves a proper quantitative analysis of the various phases—including the exact alite polymorph—of the industrial product. The rather similar structure of the two alites makes it difficult to distinguish them from their XRD patterns. This paper shows that five angular windows in the X-ray diffraction patterns can be used with synthetic alites as well as industrial compounds, to identify the nature of the actual polymorph (M1 or M3) present and the structural model to be used (with or without superstructure) in subsequent Rietveld analysis of the data.
Powder diffraction of the cubic perovskite Ba0.5Sr0.5Co0.8Fe0.2O3−δ
Authors: Koster Herman , Mertins Fre´de´ric H. B.
Published: March 2003

X-ray powder diffraction data for Ba0.5Sr0.5Co0.8Fe0.2O3−δ are reported. The powder was prepared using a metal-EDTA complexing method. The XRD data could be fitted with a primitive cubic unit cell in space group Pm3m (No. 221). The Rietveld refined unit cell parameter is ac=0.398 30(3) nm with Z=1 and Dx=5.75 g/cm3.