bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclodiene Insecticide Resistance: From Molecular to Population Genetics
Authors: ffrench-Constant Richard H. , Anthony Nicola , Aronstein Kate , Rocheleau Thomas , Stilwell Geoff
Published: July 2002

▪ Abstract  This review follows progress in the analysis of cyclodiene insecticide resistance from the initial isolation of the mutant, through cloning of the resistance gene, to an examination of the distribution of resistance alleles in natural populations. Emphasis is given to the use of a resistant Drosophila mutant as an entry point to cloning the associated γ-aminobutyric acid (GABA) receptor subunit gene, Resistance to dieldrin. Resistance is associated with replacements of a single amino acid (alanine302) in the chloride ion channel pore of the protein. Replacements of alanine302 not only directly affect the drug binding site but also allosterically destabilize the drug preferred conformation of the receptor. Resistance is thus conferred by a unique dual mechanism associated with alanine302, which is the only residue replaced in a wide range of different resistant insects. The underlying mutations appear either to have arisen once, or multiply, depending on the population biology of the pest insect. Although resistance frequencies decline in the absence of selection, resistance alleles can persist at relatively high frequency and may cause problems for compounds to which cross-resistance is observed, such as the novel fipronils.
THE PHENOMENOLOGY OF SMALL-SCALE TURBULENCE
Authors: Sreenivasan K. R. , Antonia R. A.
Published: July 2002

I have sometimes thought that what makes a man's work classic is often just this multiplicity [of interpretations], which invites and at the same time resists our craving for a clear understanding.

Wright (1982, p. 34) , on Wittgenstein's philosophy

▪ Abstract  Small-scale turbulence has been an area of especially active research in the recent past, and several useful research directions have been pursued. Here, we selectively review this work. The emphasis is on scaling phenomenology and kinematics of small-scale structure. After providing a brief introduction to the classical notions of universality due to Kolmogorov and others, we survey the existing work on intermittency, refined similarity hypotheses, anomalous scaling exponents, derivative statistics, intermittency models, and the structure and kinematics of small-scale structure—the latter aspect coming largely from the direct numerical simulation of homogeneous turbulence in a periodic box.
NONINTRUSIVE MEASUREMENTS FOR HIGH-SPEED, SUPERSONIC, AND HYPERSONIC FLOWS
Authors: Bonnet J. P. , Grésillon D. , Taran J. P.
Published: July 2002

▪ Abstract  The need to develop new diagnostics for turbulent flows at supersonic and hypersonic regimes is discussed. New experimental results can be obtained in supersonic flows by using the collective light scattering method. Typical results obtained by this method in a supersonic mixing layer are illustrated. The collective light scattering method is a directional densitometer (with a new type of spectral analysis of density fluctuations), a nonparticle anemometer, a Mach-meter (or thermometer), and a directional remote microphone. Various other optical techniques that can be applied for point, line-of-sight, or imaging measurements are reviewed. For point measurements, light-scattering methods such as Raman, Rayleigh, or electron beam fluorescence are discussed, but only briefly, since they are of little use, especially when enthalpy is very high and flow naturally bright. Emphasis is placed instead on nonlinear laser spectroscopy such as coherent anti-Stokes Raman scattering, which has recently been successful in determining temperature and density in high-enthalpy shocks. A description of diode laser absorption spectroscopy follows. A high data-rate instrument now routinely gives the static temperature and the velocity of the stream in the hot shot facility F4 of ONERA, at stagnation enthalpies in excess of 15 MJ/kg. Finally, electron beam fluorescence imaging in the same facility has made it possible to perform measurements of velocity across the external boundary layer into the flow core using a high-energy–pulsed electron gun.
NONLINEAR GRAVITY AND CAPILLARY-GRAVITY WAVES
Authors: Dias Frédéric , Kharif Christian
Published: July 2002

▪ Abstract  This review deals primarily with the bifurcation, stability, and evolution of gravity and capillary-gravity waves. Recent results on the bifurcation of various types of capillary-gravity waves, including two-dimensional solitary waves at the minimum of the dispersion curve, are reviewed. A survey of various mechanisms (including the most recent ones) to explain the frequency downshift phenomenon is provided. Recent significant results are given on “horseshoe” patterns, which are three-dimensional structures observable on the sea surface under the action of wind or in wave tank experiments. The so-called short-crested waves are then discussed. Finally, the importance of surface tension effects on steep waves is studied.
ROSSBY WAVE HYDRAULICS
Authors: Johnson ER , Clarke SR
Published: July 2002

▪ Abstract  Models are considered for rotating flows over sills, through straits, and along coasts where the variation in geometry in the flow direction is slow but otherwise unrestricted. In addition to the (rotation-modified) free surface waves of nonrotating open channel hydraulics, with their predominantly vertical signature, slow Rossby or vorticity waves are possible when the background potential vorticity varies. In all but the simplest cases the conservation of energy and momentum fluxes is no longer sufficient to determine the flow behavior. Various additional modeling assumptions are reviewed, and time-dependent finite-amplitude and weakly nonlinear theories that include long Rossby wave dynamics are summarized.
POPULATION GENETICS AND EVOLUTION OF GENOMIC IMPRINTING
Authors: Spencer Hamish G
Published: July 2002

▪ Abstract  At a small number of mammalian loci, only one of the two copies of a gene is expressed. Just which copy is expressed depends on the sex of the parent from which that copy was inherited. Such genes are said to be imprinted. The functional haploidy implied by imprinting has a number of population genetic consequences. Moreover, since diploidy is widely believed to be advantageous, the evolution of this non-Mendelian form of expression requires an explanation. Here I examine some of the theoretical and mathematical models investigating these two aspects of imprinting. For instance, the dynamics and equilibrium properties of many models of natural selection at imprinted loci are formally equivalent to models without imprinting. And different approaches to modeling the problem of the evolution of imprinting reveal the weakness of several of the apparent predictions of various verbal hypotheses about why imprinting has evolved.
DIMERIZATION AS A REGULATORY MECHANISM IN SIGNAL TRANSDUCTION
Authors: Klemm Juli D. , Schreiber Stuart L. , Crabtree Gerald R.
Published: July 2002

▪ Abstract  Dynamic protein-protein interactions are a key component of biological regulatory networks. Dimerization events—physical interactions between related proteins—represent an important subset of protein-protein interactions and are frequently employed in transducing signals from the cell surface to the nucleus. Importantly, dimerization between different members of a protein family can generate considerable functional diversity when different protein combinations have distinct regulatory properties. A survey of processes known to be controlled by dimerization illustrates the diverse physical and biological outcomes achieved through this regulatory mechanism. These include: facilitated proximity and orientation; differential regulation by heterodimerization; generation of temporal and spatial boundaries; enhancement of specificity; and regulated monomer-to-dimer transitions. Elucidation of these mechanisms has led to the design of new approaches to study and to manipulate signal transduction pathways.
USE AND ABUSE OF HUMAN GROWTH HORMONE
Authors: Neely, M.D E. Kirk , Rosenfeld, M.D Ron G.
Published: July 2002

▪ Abstract  Recombinant human growth hormone (hGH) has been available for nearly a decade. Side effects are rare. Its efficacy in promoting growth acceleration has been widely confirmed in children with GH deficiency (GHD), Turner syndrome, idiopathic short stature, chronic renal failure, and a variety of other conditions. The dramatic increase in height velocity in the first year of therapy partially attenuates in subsequent years in all patient groups, and convincing final height data are only available in GHD and Turner syndrome.

Pediatric endocrinologists continue to be troubled by definitions of GHD. Although profound GHD is relatively obvious, other patients with severe growth failure but borderline or normal endocrine testing also respond to hGH therapy. Thus many endocrinologists use auxologic criteria [e.g. low growth velocity, height <-3 standard deviation (SD), poor predicted adult height] as the de facto basis for therapy, leading to a blurred distinction between treatment of disease and enhancement of normal characteristics and, finally, raising questions about the ultimate benefit of hGH therapy. Brief clinical trials of hGH therapy in adults both with and without GHD have reported increased muscle mass, decreased fat, and improvement in quality of life. Internists may soon be faced with treatment decisions analogous to those confronting pediatricians, i.e. whether to use hGH to repair aspects of the normal aging process.
MARROW TRANSPLANTATION FOR MYELOMA
Authors: Fermand, M.D J.P. , Brouet, M.D J.C.
Published: July 2002

▪ Abstract  High-dose therapy with hemopoietic stem cell support in multiple myeloma (MM) has been used for 10 years. This approach is currently the most promising form of treatment for this disease. We review here its rationale and the results of clinical trials according to the source of hematopoietic stem cells [allogeneic or autologous, bone marrow or blood]. Finally, we discuss the ongoing uncertainties regarding the utility of this treatment and the future prospects for high-dose therapy in MM.
NONREPLACEMENT OPERATIONS FOR MITRAL VALVE REGURGITATION
Authors: Hahn, MD Chiwon , Vlahakes, MD Gus J.
Published: July 2002

▪ Abstract  Mitral valve reconstruction offers patients an important alternative to the traditional method for treating severe mitral regurgitation—mitral valve replacement. Over the last 15 years, surgical techniques have evolved for treating mitral regurgitation occurring from various anatomic mechanisms—annular dilatation, abnormal leaflet motion due to a variety of causes, or leaflet perforation. Currently, over 90% of regurgitant mitral valves of varying etiologies are amenable to nonreplacement therapy by reconstruction, with good intermediate- and long-term results. Reconstruction obviates the need for long-term anticoagulation, and thus, there has evolved a trend toward reconstruction earlier in the course of this disease, before fixed atrial fibrillation and ventricular dilatation occur.
THE MOLECULAR GENETICS OF MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A AND RELATED SYNDROMES
Authors: Moley, MD Jeffrey F.
Published: July 2002

▪ Abstract  Identification of RET gene mutations in patients at-risk for the development of the hereditary forms of medullary thyroid carcinoma has simplified management and expanded the scope of indications for surgical intervention. Patients who carry this mutation can be offered thyroidectomy at a very young age, hopefully at a point when the cancer has not yet developed or spread. Those who are found not to have inherited the mutation are spared further genetic and biochemical screening. This achievement marks a new paradigm in surgery—the recommendation that an operation be performed based on the result of a genetic test. Experience with management of patients with multiple endocrine neoplasia types 2A and 2B and with familial, non–multiple endocrine neoplasia medullary thyroid carcinoma will provide information that will aid in the future management of patients with other hereditary cancers.
ACUTE RENAL FAILURE: Role of Dialysis Membrane Biocompatibility
Authors: Pascual, MD Manuel , Swinford, MD Rita D. , Tolkoff-Rubin, MD Nina
Published: July 2002

▪ Abstract  Recent clinical studies of acute renal failure in adults have focused attention on the biocompatibility of the dialysis membrane as a possible factor influencing patient morbidity and mortality. In this article, we review the concept of dialysis membrane biocompatibility and highlight the difficulty of finding an ideal definition. We then expand on the possible roles of complement and neutrophil activation by dialysis membranes, which may prolong the recovery from acute renal failure. The results of several clinical studies analyzing the impact of dialysis membranes on the course and outcome of acute renal failure are discussed. Finally, the possible relevance of biocompatibility in continuous renal replacement therapies is emphasized.
Arrhythmias in the Athlete With Congenital Heart Disease: Guidelines For Participation
Authors: Liberthson, MD Richard R.
Published: July 2002

Advances in the diagnosis and early management of congenital heart disease in recent decades have led to increasing numbers of individuals being sufficiently well to participate in social as well as truly competitive sports. Physicians are increasingly asked whether such participation is safe, advisable, and efficacious, yet few guidelines exist to help them make these decisions. There are three apparent subgroups of patients: (a) those with mild or repaired problems, who function normally or nearly so and may fully participate; (b) those with severe functional deficit or known high risk, for whom strenuous exertion must be strictly proscribed; and (c) those who fall in between, with some limitations and some risk—these patients present a great challenge to the wisdom and clinical skill of the physician.
THE β-KETOADIPATE PATHWAY AND THE BIOLOGY OF SELF-IDENTITY
Authors: Harwood Caroline S. , Parales Rebecca E.
Published: July 2002

The β-ketoadipate pathway is a chromosomally encoded convergent pathway for aromatic compound degradation that is widely distributed in soil bacteria and fungi. One branch converts protocatechuate, derived from phenolic compounds including p-cresol, 4-hydroxybenzoate and numerous lignin monomers, to β-ketoadipate. The other branch converts catechol, generated from various aromatic hydrocarbons, amino aromatics, and lignin monomers, also to β-ketoadipate. Two additional steps accomplish the conversion of β-ketoadipate to tricarboxylic acid cycle intermediates. Enzyme studies and amino acid sequence data indicate that the pathway is highly conserved in diverse bacteria, including Pseudomonas putida, Acinetobacter calcoaceticus, Agrobacterium tumefaciens, Rhodococcus erythropolis, and many others. The catechol branch of the β-ketoadipate pathway appears to be the evolutionary precursor for portions of the plasmid-borne ortho-pathways for chlorocatechol degradation. However, accumulating evidence points to an independent and convergent evolutionary origin for the eukaryotic β-ketoadipate pathway. In the face of enzyme conservation, the β-ketoadipate pathway exhibits many permutations in different bacterial groups with respect to enzyme distribution (isozymes, points of branch convergence), regulation (inducing metabolites, regulatory proteins), and gene organization. Diversity is also evident in the behavioral responses of different bacteria to β-ketoadipate pathway-associated aromatic compounds. The presence and versatility of transport systems encoded by β-ketoadipate pathway regulons is just beginning to be explored in various microbial groups. It appears that in the course of evolution, natural selection has caused the β-ketoadipate pathway to assume a characteristic set of features or identity in different bacteria. Presumably such identities have been shaped to optimally serve the diverse lifestyles of bacteria.
REGULATORS OF APOPTOSIS ON THE ROAD TO PERSISTENT ALPHAVIRUS INFECTION
Authors: Griffin Diane E. , Hardwick J. Marie
Published: July 2002

▪ Abstract  Alphavirus infection can trigger the host cell to activate its genetically programmed cell death pathway, leading to the morphological features of apoptosis. The ability to activate this death pathway is dependent on both viral and cellular determinants. The more virulent strains of alphavirus induce apoptosis with increased efficiency both in animal models and in some cultured cells. Although the immune system clearly plays a central role in clearing virus, the importance of other cellular factors in determining the outcome of virus infections are evident from the observation that mature neurons are better able to resist alphavirus-induced apoptosis than immature neurons are, both in culture and in mouse brains. These findings are consistent with the age-dependent susceptibility to disease seen in animals. Cellular genes that are known to regulate the cell death pathway can modulate the outcome of alphavirus infection in cultured cells and perhaps in animals. The cellular bax and bak genes, which are known to accelerate cell death, also accelerate virus-induced apoptosis. In contrast, inhibitors of apoptotic cell death such as bcl-2 suppress virus-induced apoptosis, which can facilitate a persistent virus infection. Thus, the balance of cellular factors that regulate cell death may be critical in virus infections. Additional viral factors also contribute to this balance. The more virulent strains of alphavirus have acquired the ability to induce apoptosis in mature neurons, while mature neurons are resistant to cell death upon infection with less virulent strains. Here we discuss a variety of cellular and viral factors that modulate the outcome of virus infection.
Early Days of the Nerve Growth Factor Proteins
Authors: Shooter Eric M.
Published: July 2002

▪ Abstract  Adult male mouse submaxillary glands served as the preferred starting material for the isolation of the nerve growth factor (NGF) proteins in most of the isolation studies done. Two types of NGF proteins were isolated from extracts of the gland, a high-molecular-weight 7S NGF complex and a low-molecular-weight protein variously called NGF, βNGF, or 2.5S NGF. The latter, which mediated all known biological functions of NGF, were closely related forms of a basic NGF dimer in which the N and C termini of two monomers (chains) were modified by proteolytic enzymes to different extents with no effect on biological activity. The βNGF dimer showed a novel protein structure in which the two chains interacted non-covalently over a wide surface. Correspondingly, the βNGF dimer was found to be unusually stable and the form through which NGFs actions were mediated at physiological concentrations. The βNGF dimer was one of three subunits in 7S NGF; the other two were the γ subunit, an arginine esteropeptidase or kallikrein, and the α subunit, an inactive kallikrein. Two zinc ions were also present in the complex and contributed greatly to its stability. There was much debate about whether 7S NGF was a specific protein complex of interacting subunits and, if so, what functions it might play in the biology of NGF. Observations of the inhibition of the enzyme activity of the γ subunit and of the biological activity of βNGF in 7S NGF were important in determining that 7S NGF was a naturally occurring complex and the sole source of NGF in the gland extract or in saliva. Specific interactions between the active site of the γ subunit and the C-terminal arginine residues of the NGF chains, confirmed in the three-dimensional structure of 7S NGF, suggested a role for the γ subunit in pro-NGF processing during the assembly of 7S NGF. In spite of the detailed knowledge of 7S NGF structure, no information on the role of this complex in the neurobiology of NGF has emerged. With the exception of the submaxillary gland of an African rodent, no other source of NGF has been convincingly shown to synthesize the α and γ subunits, and they may well be irrelevant to NGFs actions.
MODELING RELATIVISTIC HEAVY ION COLLISIONS AT THE AGS
Authors: Kahana S. H. , Kahana D. E. , Pang Y. , Schlagel T. J.
Published: July 2002

▪ Abstract  A quantitative model, based on hadronic physics and Monte Carlo cascading, is described and applied to heavy ion collisions at BNL-AGS energies (∼ 14 GeV/u). The model was found to be in excellent agreement with particle spectra where data previously existed, for Si beams, and was able to successfully predict the spectra where data were initially absent, for Au beams. For Si + Au collisions, baryon densities of three or four times the normal nuclear matter density (ρ0) are seen in the theory, whereas for Au + Au collisions, matter at densities up to 10 ρ0 is anticipated. The possibility that unusual states of matter may be created by the Au beams and potential signatures for its observation are considered.
NUCLEAR PHYSICS WITH LIGHT-ION STORAGE RINGS
Authors: Meyer H. O.
Published: July 2002

▪ Abstract  Cooled beams in storage rings, circulating through internal targets, offer new experimental possibilities. This review summarizes the technical innovations that were required to exploit this novel environment, as well as advances in nuclear physics that are a result of it. Ongoing research and future trends are discussed as well.
LEPTOQUARK SEARCHES AT HERA AND THE TEVATRON
Authors: Acosta Darin E. , Blessing Susan K.
Published: July 2002

▪ Abstract  An unexpected excess of events with high Q2 reported by the H1 and ZEUS collaborations at HERA in early 1997 provoked speculation that the production of first-generation leptoquarks had been observed. In this article we review the anomalous HERA events, give a brief summary of the motivation for leptoquarks, and discuss the most recent searches at HERA and the Tevatron for first-, second-, and third-generation leptoquarks as well as generation-changing leptoquarks. We conclude with a short discussion of future prospects for leptoquark searches.
The CDF and DØ Upgrades for Run II
Authors: LeCompte T. , Diehl H. T.
Published: July 2002

▪ Abstract  The DØ and CDF collaborations are preparing their detectors for the Tevatron Run II. A 20-fold increase in integrated luminosity is planned for the first two years of the upcoming run, and the detector subsystems are undergoing substantial improvements to handle the higher rates as well as to better measure the products of the [Formula: see text], interactions. This review discusses the physics goals that motivate these detector enhancements and describes in detail the improvements being made to the charged particle tracking, calorimetry, muon identification, and trigger subsystems of both detectors.
NITROGEN CYCLING IN THE GUT
Authors: Fuller Malcolm F. , Reeds Peter J.
Published: July 2002

▪ Abstract  This review examines the involvement of the gastrointestinal tract in the utilization of nitrogen, the identities of the nitrogenous substances entering and leaving the gut, and the significance of this recycling in the overall nitrogen economy of the body. It is concerned with nonruminant mammals, including man.
The “Fetal Origins” Hypothesis: Challenges and Opportunities for Maternal and Child Nutrition
Authors: Rasmussen Kathleen Maher
Published: July 2002

▪ Abstract  The “fetal origins” hypothesis postulates that conditions, most likely nutritional, “program” the fetus for the development of chronic diseases in adulthood. Associations between the newborn's size at birth and various determinants or consequences of chronic diseases have been identified in many, but not all, of the available studies. It remains to be established whether these associations are causal. Remarkably little information is available on the specific role of maternal nutritional status. The role of birth weight remains difficult to interpret except as a proxy for events in intrauterine life. Unfortunately, birth weight does not make an important contribution to the population attributable risk of cardiovascular disease; lifestyle factors during adulthood make much greater contributions. Data from experimental species suggest possible mechanisms for the origin of chronic disease early in life. It is too soon to use this research as a basis for new interventions directed at pregnant women for the purpose of reducing chronic disease in their offspring.
THE ROLE OF THEhsp90-BASED CHAPERONE SYSTEM IN SIGNAL TRANSDUCTION BY NUCLEAR RECEPTORS AND RECEPTORS SIGNALING VIA MAP KINASE
Authors: Pratt William B.
Published: July 2002

▪ Abstract  The multicomponent heat-shock protein (hsp) 90–based chaperone system is an ubiquitous protein-folding system in the cytoplasm of eukaryotes. Several signal transduction systems utilize an interaction with hsp90 as an essential component of the signaling pathway. The steroid and dioxin receptors are bound to hsp90 through their hormone-binding domains, and several of them must be bound to hsp90 in order to have a ligand-binding site. The binding of ligands to these receptors promotes their dissociation from hsp90, an event that is the first step in their signaling pathways. Several protein kinases, including the Src and Raf components of the MAP kinase system, are also bound to hsp90. Genetic studies in yeast have demonstrated that hsp90 is required for normal signaling via steroid and dioxin receptors and for the activity of Src in vivo. The hsp90-based chaperone system has been reconstituted from purified components, permitting detailed analysis of the molecular basis of the chaperone's role in signal transduction.
ESTROGENS AND ATHEROSCLEROSIS
Authors: Nathan and Lauren , Chaudhuri Gautam
Published: July 2002

▪ Abstract  Estrogens prevent heart disease in women and have also been shown to retard atherogenesis in animal models. Estrogens may act at several steps in the atherogenic process to prevent cardiovascular disease. Some of the benefits of estrogens can be ascribed to their ability to favorably alter the lipoprotein profile, i.e. increase high-density lipoprotein and decrease low-density lipoprotein, and also to their ability to prevent oxidative modification of low-density lipoprotein. Other beneficial effects of estrogens include direct actions on the vascular endothelium and vascular smooth muscle, leading to a decrease in the expression of adhesion molecules involved in monocyte adhesion to endothelial cells, and to a decrease in certain chemokines involved in monocyte migration into the subendothelial space. Estrogens may also affect the later stages of atherogenesis. Finally, estrogens may modify the behavior of atherosclerotic vessels by altering their reactivity and thereby promoting vasodilation, and this may also partly account for their ability to prevent clinical events due to cardiovascular disease.
Pharmacology of Selectin Inhibitors in Ischemia/Reperfusion States
Authors: Lefer David J.
Published: July 2002

Recently, the selectin family of glycoprotein adhesion molecules (P-selectin, E-selectin, and L-selectin) has been implicated in the pathogenesis of a number of inflammatory disease states. The selectins modulate the early adhesive interactions between circulating neutrophils and the endothelium. Both P-selectin and E-selectin can be expressed on the surface of endothelial cells following stimulation by a number of inflammatory mediators. In contrast, L-selectin is constitutively expressed on the surface of neutrophils at very high levels. In addition, neutrophils also express ligands for the endothelial selectins, including the carbohydrate sialyl Lewisx and the high-affinity ligand P-selectin glycoprotein ligand 1, which facilitate neutrophil-endothelial interactions. Selectins have been extensively investigated in ischemia/reperfusion injury states. The study of selectin involvement in ischemia/ reperfusion injury has been facilitated by the development of highly specific selectin antagonists, including monoclonal antibodies, carbohydrates, small molecule inhibitors, and soluble forms of P-selectin glycoprotein ligand 1. This article reviews the results of current studies of selectin antagonists in experimental models of ischemia/ reperfusion injury.
Pharmacology of Cloned P2X Receptors
Authors: North R. Alan , Surprenant Annmarie
Published: July 2002

There are seven P2X receptor cDNAs currently known. Six homomeric (P2X1, P2X2, P2X3, P2X4, P2X5, P2X7) and three heteromeric (P2X2/P2X3, P2X4/P2X6, P2X1/P2X5) P2X receptor channels have been characterized in heterologous expression systems. Homomeric P2X1 and P2X3 receptors are readily distinguishable by their rapid desensitization, the agonist action of αβmethyleneATP, and the block by 2′,3′-O-(2,4,6-trinitrophenyl)-ATP. P2X2 receptors are unique among homomeric forms in their potentiation by low pH. Homomeric P2X4 receptors are much less sensitive to antagonism by suramin and pyridoxal 5-phosphate-6-azo-2′,4′-disulfonic acid. Homomeric P2X7 receptors are the only form in which 2′,3′-O-(4-benzoylbenzoyl)-ATP is more potent than ATP. The heteromeric P2X2/P2X3 receptor resembles P2X2 in slow desensitization kinetics and potentiation by low pH and is similar to P2X3 with respect to agonism by αβmethyleneATP and block by 2′,3′-O-(2,4,6-trinitrophenyl)-ATP. Other agonists, antagonists, and ions that can be used to differentiate among the receptors are discussed.
Regulation ofCYP3AGene Transcription by the Pregnane X Receptor
Authors: Goodwin Bryan , Redinbo Matthew R. , Kliewer Steven A.
Published: July 2002

The pregnane X receptor (PXR) is a promiscuous nuclear receptor that has evolved to protect the body from toxic chemicals. PXR is activated by a structurally diverse collection of xenobiotics, including several widely used prescription drugs. Various lipophilic compounds produced by the body, such as bile acids and steroids, also activate PXR. PXR stimulates the transcription of cytochrome P450 3A monooxygenases and other genes involved in the detoxification and elimination of these potentially harmful chemicals. Assays that detect PXR activation have important implications for the design of future drugs in two respects. On the one hand, PXR activation assays can be used to determine whether candidate drugs are likely to induce CYP3A gene expression and interact with other medicines. On the other hand, PXR agonists may prove useful in the treatment of diseases in which toxic metabolites accumulate, such as cholestatic liver disease.
KINETICS IN SOLIDS
Authors: Vyazovkin S. , Wight C. A.
Published: July 2002

▪ Abstract  The kinetics of solid state reactions generally cannot be assumed to follow simple rate laws that are applicable to gas-phase reactions. Nevertheless, a widely practiced method for extracting Arrhenius parameters from thermal analysis experiments involves force fitting of experimental data to simple reaction-order kinetic models. This method can produce significant errors in predicted rates outside the experimental range of temperatures, and it is of limited utility for drawing mechanistic conclusions about reactions. In this review, we discuss how an alternative “model-free” approach to kinetic analysis, which is based on the isoconversional method, can overcome some of these limitations.
COMPUTER SIMULATIONS WITH EXPLICIT SOLVENT: Recent Progress in the Thermodynamic Decomposition of Free Energies and in Modeling Electrostatic Effects
Authors: Levy Ronald M. , Gallicchio Emilio
Published: July 2002

▪ Abstract  This review focuses on recent progress in two areas in which computer simulations with explicit solvent are being applied: the thermodynamic decomposition of free energies, and modeling electrostatic effects. The computationally intensive nature of these simulations has been an obstacle to the systematic study of many problems in solvation thermodynamics, such as the decomposition of solvation and ligand binding free energies into component enthalpies and entropies. With the revolution in computer power continuing, these problems are ripe for study but require the judicious choice of algorithms and approximations. We provide a critical evaluation of several numerical approaches to the thermodynamic decomposition of free energies and summarize applications in the current literature. Progress in computer simulations with explicit solvent of charge perturbations in biomolecules was slow in the early 1990s because of the widespread use of truncated Coulomb potentials in these simulations, among other factors. Development of the sophisticated technology described in this review to handle the long-range electrostatic interactions has increased the predictive power of these simulations to the point where comparisons between explicit and continuum solvent models can reveal differences that have their true physical origin in the inherent molecularity of the surrounding medium.
PHYSIOLOGY OF ISOLATED GASTRIC ENDOCRINE CELLS
Authors: Sachs George , Zeng Ningxin , Prinz Christian
Published: July 2002

▪ Abstract  The regulation of gastric acid secretion is achieved in the periphery by interplay between three major gastric endocrine cells: the enterochromaffin-like (ECL) cell, the gastrin or G cell, and the somatostatin or D cell. Regulation of these cells is via stimulatory or inhibitory paracrine, endocrine, and neural pathways. Upregulation of ECL function is determined by activation of CCK-B receptors, by gastrin, and by activation of β-adrenergic receptors, as well as by acetylcholine in some (10–29%) of the cells. Gastrin and acetylcholine produce typical biphasic calcium signals. Inhibition of ECL cell histamine release and calcium signaling is produced by somatostatin acting at a type 2 receptor, histamine acting at a histamine-3 receptor, and by peptide PYY. Stimulation of ECL cells results in activation of chloride channels, and there is evidence that voltage-dependent calcium channels, along with the receptor-operated calcium channels, also are responsible for elevation of [Ca]i. Depolarization-activated K+ channels presumably restore the potential after depolarization by activation of the chloride channel. The D cell is activated by either gastrin or CCK and appears to be inhibited by acetylcholine and somatostatin. The G cell is activated by acetylcholine and gastrin-releasing peptide (GRP) and is inhibited by somatostatin. The functional integration of these three cell types is the primary determinant of the degree of stimulation of the parietal cell.
Molecular Diversity of Pacemaker Ion Channels
Authors: Kaupp U Benjamin , Seifert Reinhard
Published: July 2002

▪ Abstract  Ionic currents activated by hyperpolarization and regulated by cyclic nucleotides were first discovered more than 20 years ago. Recently the molecular identity of the underlying channels has been unveiled. The structural features of the protein sequences are discussed and related to the mechanisms of activation, selectivity for cyclic nucleotides, and ion permeation. Coverage includes a comparison of the biophysical properties of recombinant and native channels and their significance for the physiological functions of these channels.
Aromatase—A Brief Overview
Authors: Simpson Evan R. , Clyne Colin , Rubin Gary , Boon Wah Chin , Robertson Kirsten , Britt Kara , Speed Caroline , Jones Margaret
Published: July 2002

▪ Abstract  There is growing awareness that androgens and estrogens have general metabolic roles that are not directly involved in reproductive processes. These include actions on vascular function, lipid and carbohydrate metabolism, as well as bone mineralization and epiphyseal closure in both sexes. In postmenopausal women, as in men, estrogen is no longer solely an endocrine factor but instead is produced in a number of extragonadal sites and acts locally at these sites in a paracrine and intracrine fashion. These sites include breast, bone, vasculature, and brain. Within these sites, aromatase action can generate high levels of estradiol locally without significantly affecting circulating levels. Circulating C19steroid precursors are essential substrates for extragonadal estrogen synthesis. The levels of these androgenic precursors decline markedly with advancing age in women, possible from the mid-to-late reproductive years. This may be a fundamental reason why women are at increased risk for bone mineral loss and fracture, and possibly decline of cognitive function, compared with men. Aromatase expression in these various sites is under the control of tissue-specific promotors regulated by different cohorts of transcription factors. Thus in principle, it should be possible to develop selective aromatase modulators (SAMs) that block aromatase expression, for example, in breast, but allow unimpaired estrogen synthesis in other tissues such as bone.
ONE PHYTOPATHOLOGIST'S GROWTH THROUGH IPM TO HOLISTIC PLANT HEALTH: The Key to Approaching Genetic Yield Potential
Authors: Browning J. Artie
Published: July 2002

▪ Abstract  I relate my becoming a phytopathologist and my very satisfying growth into and beyond IPM to holistic plant health, and puzzle over paradigms that have prevented our accepting the overwhelming logic of (a) seeking defensible disease-loss data to justify funding and guide research and management priorities, (b) managing genetic diversity to retard pathogen development, (c) conserving genetic diversity in situ, and (d) educating and training general practitioner plant doctors. These multidisciplinary health care professionals are key to overcoming sources of stress that cause major world crops to yield only 15–20% of their genetic potential, on average. Thus, plant doctors give hope for approaching attainable yield and feeding a hungry world—if, simultaneously, human population growth is reduced. The plant health movement has the potential to effect the greatest change in world agriculture since the Green Revolution, and the DPH/M to become plant agriculture's most important single degree program.
FREEDOM TO OPERATE: Intellectual Property Protection in Plant Biology and Its Implications for the Conduct of Research
Authors: Kimpel Janice A.
Published: July 2002

▪ Abstract  Research endeavors are being affected by issues involving intellectual property (patents, copyrights, and trademarks). The acquisition of rights in intellectual property by universities can result in the transfer of new innovations to the private sector, with the university recouping a share of the profits for support of further scientific research. Intellectual property rights available for new plant cultivars include plant patents, plant variety protection certificates, plant breeder's rights, and utility patents. Under the patent laws, there is no explicit exemption for research use, so researchers are increasingly being required to execute materials transfer agreements to obtain permission to use patented materials, such as techniques, genes, seeds, and cell lines, in laboratory research and in breeding programs. Research scientists must educate themselves on these issues so that they can make informed decisions regarding their research practices and the licensing of their discoveries.
Legacy for the Millennium: A Century of Progress in Plant Pathology
Authors: Sequeira Luis
Published: July 2002

Plant pathology came of age at the turn of this century and we can be proud of the many significant contributions it has made to fundamental research as well as to service to growers. The twenty-first century will present our profession with dramatic challenges to meet the demands for increased food, fiber, and fuel production from a declining agricultural base. This can be accomplished only if plant pathology retains its integrity as a profession and remains abreast of advancements in the fields of biotechnology and communications.
THE INTELLECTUAL LEGACY OF LEO STRAUSS (1899–1973)
Authors: Behnegar Nasser
Published: July 2002

▪ Abstract  Leo Strauss revitalized the potential of political philosophy, which had been buried by positivism and historicism. Strauss was both impressed by and dissatisfied with the contemporary criticism of rationalism. Studying the history of political philosophy, he discovered that classical rationalism is not open to the criticism of rationalism because it does not begin by assuming the goodness of philosophy. Classical political philosophy overcomes nihilism not by proving the existence of universal rules of conduct, but by seeing what is highest in man. Modern philosophers departed from the classical approach in an unsuccessful attempt to meet the challenge of revealed religion. This failure led them to engage in a political-scientific project whose ultimate purpose was to refute revealed religion. Although the project failed, it led to the concealment of the most fundamental problems of human beings. The recovery of those problems is Strauss's great legacy.
DETERRENCE AND INTERNATIONAL CONFLICT: Empirical Findings and Theoretical Debates
Authors: Huth Paul K.
Published: July 2002

▪ Abstract  The utility of military threats as a means to deter international crises and war has been a central topic of international relations research. Rational choice models have provided the foundation for theorizing about the conditions under which conventional deterrence is likely to succeed or fail. Rational deterrence theorists have focused on four sets of variables: the balance of military forces, costly signaling and bargaining behavior, reputations, and interests at stake. Over the past two decades, scholars have tested propositions from rational deterrence theory utilizing both statistical and comparative case study methods. Although the empirical results from these tests have supported a number of hypotheses derived from the theoretical literature, they have also challenged some theoretical arguments and have sparked vigorous debates about both theory and research designs for conducting empirical research.
PERSPECTIVES ON THE PLACE OF ENVIRONMENTAL HEALTH AND PROTECTION IN PUBLIC HEALTH AND PUBLIC HEALTH AGENCIES
Authors: Kotchian S.
Published: July 2002

▪ Abstract  The field of environmental health and protection and the entire field of public health have repeatedly found themselves isolated from one another, unable to articulate the definition, mission, and goals of public health and the essential role for environmental health and protection in the provision of a healthy ecological and human environment. Environmental agencies often forget that they, too, are public health agencies; public health agencies that have had environmental health functions have divided and abdicated their environmental responsibilities, considering these to be “regulatory” rather than public health. This article reviews the history of environmental health and protection, its involvement within the field of public health, its eventual separation from other public health programs with resulting benefits and consequences, and what the future may hold for environmental health and protection activities as well as for the broader scope of public health of which these activities are a part.
Physician Payment Policies: Impacts and Implications
Authors: Rice Thomas
Published: July 2002

▪ Abstract  This paper reviews recent changes in physician payment policies, examines evidence on their impacts, and discusses their implications for researchers and policy makers. It first develops a conceptual framework to help explore the economic incentives inherent in different physician payment schemes. It then reviews evidence on the impacts of recent changes in physician payment methods; first, for fee-for-service, and then for capitated systems like HMOs. It concludes that much more research needs to be conducted on HMOs to determine the impact of different physician payment incentives on utilization, expenditures, clinical outcomes, and patient satisfaction.
Personal Reflections on Occupational Health in the Twentieth Century: Spiraling to the Future
Authors: Cullen Mark R.
Published: July 2002

▪ Abstract  The history of occupational health in the United States during the twentieth century demonstrates pendular swings, with periods of rapid progress followed by periods of reversal. Happily, the last three decades have witnessed the most impressive gains, with establishment of a near-universal system for regulating conditions in the workplace, legitimization and growth of the occupational health professions, a marked increase in scientific research, most notably epidemiology, and the transfer of knowledge about occupational health to affected workers and the larger US population. Not surprisingly, rates of injury and illness have fallen.

However, analysis of these cyclical historic changes suggests that extrinsic factors—broad social currents, changes in health care financing, and societal perceptions of health and disease—have dominated over enhanced scientific knowledge, technologic changes or professional achievements, usually the determinants of medical or public health advances. Practitioners of occupational health are not, and have never been, in a particularly advantageous position to fashion future events in their own field, and the current situation, however encouraging, is likely no exception.
IMMUNIZATION REGISTRIES IN THE UNITED STATES: Implications for the Practice of Public Health in a Changing Health Care System
Authors: Wood David , Saarlas Kristin N. , Inkelas Moira , Matyas Bela T.
Published: July 2002

▪ Abstract  Although immunization rates among children are rising across the country, rates in inner-city areas have remained at ∼50%–60%, ≤30% lower than corresponding suburban or state immunization levels. The failure to raise immunization levels in poor, underserved populations is caused in part by the lack of timely and accurate child-specific immunization information for providers and parents. Immunization registries are a new tool in health care that can be used to address these and other barriers to effective immunization delivery. Moreover, immunization registries have the potential to help health care officials track and improve delivery for a broad range of important child health services. An immunization registry is a computerized database of information on children (usually preschool-age children) in a defined population (e.g. those enrolled in a health maintenance organization or living in a specific geographic area), which is used to record and track all immunizations received by each child. The registry receives the information primarily from public and private providers that administer immunizations, as well as from parents, schools, and other agencies. A fully functioning immunization registry can be used to identify individual children in need of immunizations and to report on immunization rates by population characteristics such as child age, assigned provider, or geographic area (e.g. neighborhood, city). Today, >250 local public health departments have immunization registries that are in various stages of planning or development. Only a small number of these registries meet the minimum functional criteria of maintaining records on 95% of all eligible 2-year-old children in the target population and providing an electronic immunization record that is accessible to providers. Nascent immunization registries represent innovative technologic solutions to the challenge of monitoring health problems and health care access on a population basis. This is a fundamental activity of public health agencies, but one that is increasingly shared by large health maintenance organizations. The study of the development of immunization registries across the United States provides an important case study for how public health agencies will use the rapidly developing health information infrastructure to perform health assessment and health assurance activities in a managed care environment.