bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Impacts on Atmospheric Chemistry
Authors: Crutzen PJ , Lelieveld J
Published: July 2002

An overview is given of the main anthropogenic influences on the chemistry of the atmosphere. Industrial and agricultural activities have altered the chemical composition of the atmosphere in many important ways, which is reflected especially in the distribution and concentrations of ozone in the troposphere and stratosphere. On one hand, as a result of industrial chlorofluorocarbon emissions, ozone has been depleted in unexpected major ways in the polar stratosphere. On the other hand, especially as a result of NO emissions, tropospheric ozone has increased both in the industrial mid-latitude regions and at low latitudes, in the latter mostly because of tropical biomass burning. In the future, growing anthropogenic emissions by developing nations will have an additional effect on the climate and the self-cleaning (oxidation) power of the atmosphere.
RURAL ENERGY IN DEVELOPING COUNTRIES: A Challenge for Economic Development
Authors: Barnes Douglas F. , Floor Willem M.
Published: July 2002

▪ Abstract  The energy problems of the developing world are both serious and widespread. Lack of access to sufficient and sustainable supplies of energy affects as much as 90% of the population of many developing countries. Some 2 billion people are without electricity; a similar number remain dependent on fuels such as animal dung, crop residues, wood, and charcoal to cook their daily meals. Without efficient, clean energy, people are undermined in their efforts to engage effectively in productive activities or to improve their quality of life. Developing countries are facing two crucial—and related—problems in the energy sector. The first is the widespread inefficient production and use of traditional energy sources, such as fuelwood and agricultural residues, which pose economic, environmental, and health threats. The second is the highly uneven distribution and use of modern energy sources, such as electricity, petroleum products, and liquefied or compressed natural gas, which pose important issues of economics, equity, and quality of life. To address these problems, this paper evaluates some successful programs and recommends that governments support market-oriented approaches that make the energy market equally accessible and attractive to local investors, communities, and consumers. Such approaches ideally improve access to energy for rural and poor people by revising energy pricing and by making the first costs of the transition to modern and more sustainable uses of energy more affordable.
INTEGRATED ANALYSIS FOR ACID RAIN IN ASIA: Policy Implications and Results of RAINS-ASIA Model
Authors: Shah Jitendra , Nagpal Tanvi , Johnson Todd , Amann Markus , Carmichael Gregory , Foell Wesley , Green Collin , Hettelingh Jean-Paul , Hordijk Leen , Li Jia , Peng Chao , Pu Yifen , Ramankutty Ramesh , Streets David
Published: July 2002

▪ Abstract  Fossil fuels account for about 80% of energy consumption in Asia. Because of its abundance and easy recoverability, especially in India and China, coal will remain the fuel of choice in the foreseeable future. If current trends continue, sulfur dioxide emissions from Asia may soon equal the emissions from North America and Europe combined. These trends portend a variety of local, regional, and global environmental impacts. Acid rain damages human health, ecosystems, and built surfaces. Many ecosystems will be unable to absorb these increased acidic depositions, leading to irreversible ecosystem damage with far-reaching implications for health, forestry, agriculture, fisheries, and tourism. RAINS-ASIA is a scenario-generating tool used to estimate the extent of damages caused by acid rain and to review the costs and impacts of alternatives to provide a look into the future. Its use extends from national-, regional-, and city-scale evaluation and inputs for cost-effective options analyses, to international negotiations on transboundary pollution.
Insect Performance on Experimentally Stressed Woody Plants: A Meta-Analysis
Authors: Koricheva Julia , Larsson Stig , Haukioja Erkki
Published: July 2002

▪ Abstract  In this review, we test the hypothesis that abiotic stress increases the suitability of plants as food for herbivores. We conducted a meta-analysis that included 70 experimental studies in which insect performance was measured on woody plants subjected to water stress, pollution, and/or shading. Overall, plant stress had no significant effect on insect growth rate, fecundity, survival, or colonization density. We found great variation, however, in the magnitude and direction of insect responses among studies, most of which was related to insect feeding guild. In general, boring and sucking insects performed better on stressed plants, whereas plant stress adversely affected gall-makers and chewing insects. Reduction in performance of chewers was greater on stressed slow-growing plants than on stressed fast growers. Reproductive potential of sucking insects was increased by pollution but reduced by water stress. In some cases where sample sizes were small or the treatment periods short, apparent differences in insect responses to stress were probably artifacts due to inappropriate experimental design.
VORTEX DYNAMICS IN TURBULENCE
Authors: Pullin D. I. , Saffman P. G.
Published: July 2002

▪ Abstract  We survey attempts to construct vortex models of the inertial-range and fine-scale range of high Reynolds number turbulence. An emphasis is placed on models capable of quantitative predictions or postdictions.
SURFACEPRESSUREMEASUREMENTSUSINGLUMINESCENTCOATINGS
Authors: Bell James H , Schairer Edward T , Hand Lawrence A , Mehta Rabindra D
Published: July 2002

▪ Abstract  An optical technique is described that is often used nowadays to measure surface pressures on wind tunnel models and flight vehicles. The technique uses luminescent coatings, which are painted on the model surface, excited by light of appropriate wavelength, and imaged with digital cameras. The intensity of the emitted light is inversely proportional to the surface pressure. Hence, the surface pressures can be measured efficiently and affordably with a high spatial resolution. The theory and chemistry of how such coatings work and the parameters that affect them are presented. The required hardware and software are described, with emphasis on the different measurement systems and procedures. The various error sources are discussed, and correction schemes that can be used to minimize them are presented. Sample results, covering a wide range of conditions and applications, are presented and discussed.
COMPARATIVE DNA ANALYSIS ACROSS DIVERSE GENOMES
Authors: Karlin Samuel , Campbell Allan M. , Mrázek Jan
Published: July 2002

▪ Abstract  We review concepts and methods for comparative analysis of complete genomes including assessments of genomic compositional contrasts based on dinucleotide and tetranucleotide relative abundance values, identifications of rare and frequent oligonucleotides, evaluations and interpretations of codon biases in several large prokaryotic genomes, and characterizations of compositional asymmetry between the two DNA strands in certain bacterial genomes. The discussion also covers means for identifying alien (e.g. laterally transferred) genes and detecting potential specialization islands in bacterial genomes.
SOMATIC HYPERMUTATION OF IMMUNOGLOBULIN GENES
Authors: Wagner Simon D. , Neuberger Michael S.
Published: July 2002

▪ Abstract  The relationship between somatic hypermutation and affinity maturation in the mouse is delineated. Recent work on the anatomical and cellular site of this process is surveyed. The molecular characteristics of somatic hypermutation are described in terms of the region mutated and the distinctive patterns of nucleotide changes that are observed. The results of experiments utilizing transgenic mice to find out the minimum cis-acting sequences required to recruit hypermutation are summarized. The hypothesis that V gene sequences have evolved in order to target mutation to certain sites but not others is discussed. The use that different species make of somatic hypermutation to generate either the primary or secondary B cell repertoire is considered. Possible molecular mechanisms for the hypermutation process and future goals of research are outlined.
PATHWAYS AND STRATEGIES FOR DEVELOPING A MALARIA BLOOD-STAGE VACCINE
Authors: Good Michael F. , Kaslow David C. , Miller Louis H.
Published: July 2002

▪ Abstract  In the past 10 years, our knowledge of the malaria parasite has increased enormously: identification and analysis of parasite antigens, demonstration of protection of monkeys and mice following immunization with these antigens, and better understanding of the mechanisms of immunity to malaria and the pathogenesis of disease in malaria. Powerful new adjuvants have been developed, some of which—it is hoped—will be suitable for human use. Recently, a successful human trial of a vaccine aimed at sporozoites (the stage inoculated by mosquitoes) was completed. However, it is the red blood cell stage of the parasite that causes disease, and it is against this stage—in which the parasite grows at an exponential rate—that it has proven very difficult to induce a protective immune response by vaccination. This review focuses on recent exciting developments toward a blood-stage vaccine. We analyze the major obstacles to vaccine development and outline a strategy involving public- and industry-funded research that should result in development of a vaccine.
Dendritic Cells in Cancer Immunotherapy
Authors: Fong Lawrence , Engleman Edgar G.
Published: July 2002

The potential to harness the potency and specificity of the immune system underlies the growing interest in cancer immunotherapy. One such approach uses bone marrow–derived dendritic cells, phenotypically distinct and extremely potent antigen-presenting cells, to present tumor-associated antigens and thereby generate tumor-specific immunity. Support for this strategy comes from animal studies that have demonstrated that dendritic cells, when loaded ex vivo with tumor antigens and administered to tumor-bearing hosts, can elicit T cell–mediated tumor destruction. These observations have led to clinical trials designed to investigate the immunologic and clinical effects of antigen-loaded dendritic cells administered as a therapeutic vaccine to patients with cancer. In the design and conduct of such trials, important considerations include antigen selection, methods for introducing the antigen into MHC class I and II processing pathways, methods for isolating and activating dendritic cells, and route of administration. Although current dendritic cell–based vaccination methods are cumbersome, promising results from clinical trials in patients with malignant lymphoma, melanoma, and prostate cancer suggest that immunotherapeutic strategies that take advantage of the antigen presenting properties of dendritic cells may ultimately prove both efficacious and widely applicable to human tumors.
Viral Subversion of the Immune System
Authors: Tortorella Domenico , Gewurz Benjamin E. , Furman Margo H. , Schust Danny J. , Ploegh Hidde L.
Published: July 2002

This review describes the diverse array of pathways and molecular targets that are used by viruses to elude immune detection and destruction. These include targeting of pathways for major histocompatibility complex-restricted antigen presentation, apoptosis, cytokine-mediated signaling, and humoral immune responses. The continuous interactions between host and pathogens during their coevolution have shaped the immune system, but also the counter measures used by pathogens. Further study of their interactions should improve our ability to manipulate and exploit the various pathogens.
Patterned Magnetic Recording Media
Authors: Ross CA
Published: July 2002

▪ Abstract  Continuing increases in the areal density of hard disk drives will be limited by thermal instability of the thin film medium. Patterned media, in which data are stored in an array of single-domain magnetic particles, have been suggested as a means to overcome this limitation and to enable recording densities of up to 150 Gbit cm−2 (1 Tbit inch−2) to be achieved. However, the implementation of patterned media requires fabrication of sub-50-nm features over large areas and the design of recording systems that differ substantially from those used in conventional hard drives. This review describes patterned media, including the fabrication of arrays of small magnetic particles and their magnetic properties, such as domain structure, reversal mechanisms, thermal stability, and interactions. The practical implementation of patterned media recording schemes is assessed.
TREATMENT OF VENTRICULAR ARRHYTHMIAS AFTER RECOVERY FROM MYOCARDIAL INFARCTION
Authors: Mitchell, M.D L. Brent
Published: July 2002

▪ Abstract  Demonstrated associations between postmyocardial infarction ventricular arrhythmias and a higher subsequent risk of both sudden and all-cause mortality have prompted a search for effective and safe treatment modalities. Recently completed clinical trials have provided a rationale for treatment recommendations in some specific settings. Beta-blocking therapy is recommended for postinfarction patients with frequent or complex ventricular premature beats. In contrast, calcium antagonist therapy is not helpful in these cases, and Class I antiarrhythmic therapy is actually harmful. Early indications of benefit from Class III antiarrhythmic therapies, particularly amiodarone, are under evaluation in large trials. Patients with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) occuring late after myocardial infarction require therapy. Viable therapeutic methods include individualized antiarrhythmic therapy selected by the noninvasive approach, individualized antiarrhythmic therapy selected by the invasive approach, empiric amiodarone therapy, transcatheter or surgical ablative therapy (for VT), and use of an implantable cardioverter defibrillator. Clinical trial data have yet to determine which of these approaches is most effective under which circumstances. Postinfarction patients with nonsustained VT are the focus of several ongoing treatment trials. Early data suggest that risks requiring specific therapy are reached only by those patients who also have significant left ventricular dysfunction. The presence of inducible sustained ventricular tachycardia at an electrophysiologic study may further risk stratify such patients. High-risk patients with nonsustained ventricular tacycardia, left ventricular dysfunction, and inducible sustained ventricular tachycardia should participate in ongoing clinical trials. In the absence of this opportunity, intensive treatment should be considered.
MOLECULAR EVENTS IN THE PATHOGENESIS OF HEPADNAVIRUS-ASSOCIATED HEPATOCELLULAR CARCINOMA
Authors: Robinson, M.D William S.
Published: July 2002

▪ Abstract  Chronic hepadnavirus infection is associated with hepatocellular carcinoma (HCC) in natural hosts such as humans, woodchucks, and Beechey ground squirrels. Several possible oncogenic mechanisms have been identified, including a potential role of the hepadnavirus x (hbx) gene, which transactivates transcription regulated by certain cis-acting sequences, e.g. regulatory sequences of the hepatitis B virus (HBV) and heterologous regulatory sequences of other viruses and cellular genes. The oncogenic potential of hbx is suggested by the observation of HCCs in hbx transgenic mice, the oncogenic transformation of cells expressing hbx in culture, and the transactivation of oncogenes c-myc and c-jun by hbx. Cis-activation of cellular oncogenes N-myc and c-myc by viral promoter insertion has been a common finding in woodchuck hepatitis virus (WHV)-associated HCCs of woodchucks. No such cis-activation of any cellular gene has been shown in virus-associated HCCs of ground squirrels or humans. Amplification and overexpression of the c-myc gene has been a common finding in HCCs of ground squirrels, and is rare in woodchuck or human HCCs. Point mutations in the p53 gene and allelic deletion of p53 have been common findings in human HCCs, but have not been found in HCCs in woodchucks and have been found rarely in ground squirrels. How each of these genetic changes in the different hosts contributes to HCC remains to be determined, but apparently different changes in different HCCs of hepadnavirus-infected hosts suggest that several separate genetic events may contribute to the development of HCC. These events may differ in each host, and some may not result from a direct virus-specific mechanism. Chronic hepadnavirus infection is often associated with chronic necroinflammatory liver disease and cirrhosis, a pathologic process common to several other risk factors for HCC. This suggests that this pathologic process (necroinflammatory disease) may be hepatocarcinogenic regardless of the inciting agent. Thus hepadnavirus infection may play an important role in the development of HCC by causing chronic hepatitis and HCC with the same mechanisms by which other risk factors for HCC cause chronic necroinflammatory liver disease and HCC.
CLINICAL TRIALS IN PULMONARY HYPERTENSION
Authors: Badesch, MD David B.
Published: July 2002

▪ Abstract  Progress in treatment of pulmonary hypertension has been impaired by the lack of formal clinical trials. This is now beginning to change, and the impact on our approach to treating patients with pulmonary hypertension is substantial. As with other relatively uncommon medical disorders, randomized, controlled, multi-center trials are needed to assess the safety and efficacy of potential therapeutic modalities. Treatments showing promise at the level of small pilot studies within a single center should be studied more rigorously.
Malaria: New Developments in Treatment and Prevention
Authors: Newton, BM, DPhil, MRCP Paul , White, DSc, MD, FRCP Nicholas
Published: July 2002

Malaria still kills some 0.5–2.5 million people per year in the tropics. Resistance to the cheap, most commonly used antimalarials continues to spread alarmingly and could outpace drug development. The artemisinin derivatives have had an important clinical impact both on the treatment of resistant falciparum malaria and on the incidence of disease in low-transmission areas. A few promising new antimalarials are being tested clinically but there is an imperative need for cheap, well-tolerated drugs that can be used in short courses, and for strategies to delay the onset of drug resistance. Bed nets have been shown to reduce the incidence of severe malaria in many areas but an effective vaccine is urgently needed.
Nonsteroidal Anti-Inflammatory Drugs and Cancer Prevention
Authors: Baron John A. , Sandler Robert S.
Published: July 2002

▪ Abstract  Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, appear to have clinically significant anticarcinogenic effects in the gastrointestinal tract. Epidemiological data indicate that use of these drugs is inversely associated with the risk of sporadic colorectal cancer, and clinical trials among patients with familial polyposis coli show that NSAIDs can lead to the regression of large bowel adenomas. Animal studies have reported a similar efficacy of NSAIDs against experimental carcinogenesis. A consistent pattern in this research is that continued long-term use of NSAIDs is required for an anticancer effect—up to 15 or 20 years before a reduced risk of colorectal cancer appears. Epidemiological data also suggest possible protective effects in the stomach and esophagus. The mechanisms underlying any chemopreventive effect of NSAIDs are not clear. Inhibition of cyclooxygenase is one possibility, but pathways independent of cyclooxygenase and prostaglandins are also possible.
Acute Respiratory Distress Syndrome: Physiology and New Management Strategies
Authors: Weinacker Ann B. , Vaszar Laszlo T.
Published: July 2002

▪ Abstract  The acute respiratory distress syndrome (ARDS) has been recognized for more than three decades as a cause of respiratory failure in patients with a variety of illnesses. Clinically, it is characterized by pulmonary edema, refractory hypoxemia, diffuse pulmonary infiltrates, and altered lung compliance. Pathologically, it is distinguished by infiltration of the lungs with inflammatory cells, interstitial and alveolar edema, hyaline membrane formation, and ultimately fibrosis. Although we have learned much about the pathophysiology of this inflammatory syndrome since its earliest descriptions, ARDS continues to claim the lives of 40%–70% of its victims. Many treatment strategies have been used to prevent or treat ARDS, but thus far the most encouraging strategy to prevent lung injury and improve survival is mechanical ventilation with low tidal volumes and high levels of positive end-expiratory pressure.
GENETICALLY ENGINEERED SYNTHESIS OF NATURAL PRODUCTS: From Alkaloids to Corrins
Authors: Roessner Charles A. , Ian Scott A.
Published: July 2002

Because many natural products are of biological and medicinal importance, methods are continually being sought for studying their biosynthetic pathways, which may eventually result in increased production and the generation of novel compounds. Advances in genetic engineering have enabled the homologous or heterologous expression of many natural product biosynthetic genes from divergent sources, resulting in a supply of enzymes not readily available by isolation from the producing organism. Mixing and matching of these enzymes in cell-free reactions can provide information, not available by any other means, about enzyme mechanisms, pathway intermediates, and possible variations in the structure of the final product.
METABOLIC CHANGES OF THE MALARIA PARASITE DURING THE TRANSITION FROM THE HUMAN TO THE MOSQUITO HOST
Authors: Lang-Unnasch N. , Murphy A. D.
Published: July 2002

▪ Abstract  Plasmodium falciparum is an obligate human parasite that is the causative agent of the most lethal form of human malaria. Transmission of P. falciparum to a new human host requires a mosquito vector within which sexual replication occurs. P. falciparum replicates as an intracellular parasite in man and as an extracellular parasite in the mosquito, and it undergoes multiple developmental changes in both hosts. Changes in the environment and the activities of parasites in these various life-cycle stages are likely to be reflected in changes in the metabolic needs and capabilities of the parasite. Most of our knowledge of the metabolic capabilities of P. falciparum is derived from studies of the asexual erythrocytic cycle of the parasite, the portion of the parasite life cycle found in infected humans that is responsible for malarial symptoms. Efforts to control transmission and to understand the sometimes unique biology of this parasite have led to information about the metabolic capabilities of sexual and/or sporogonic stages of these parasites. This review focuses on comparing and contrasting the carbohydrate, nucleic acid, and protein synthetic capabilities of asexual erythrocytic stages and sexual stages of P. falciparum.
Glial Control of Neuronal Development
Authors: Lemke Greg
Published: July 2002

▪ Abstract  Reciprocal interactions between differentiating glial cells and neurons define the course of nervous system development even before the point at which these two cell types become definitively recognizable. Glial cells control the survival of associated neurons in both Drosophila and mammals, but this control is dependent on the prior neuronal triggering of glial cell fate commitment and trophic factor expression. In mammals, the growth factor neuregulin-1 and its receptors of the ErbB family play crucial roles in both events. Similarly, early differentiating neurons and their associated glia rely on reciprocal signaling to establish the basic axon scaffolds from which neuronal connections evolve. The importance of this interactive signaling is illustrated by the action of glial transcription factors and of glial axon guidance cues such as netrin and slit, which together regulate the commissural crossing of pioneer axons at the neural midline. In these and related events, the defining principle is one of mutually reinforced and mutually dependent signaling that occurs in a network of developing neurons and glia.
THE WORLD WIDE WEB AND HIGH-ENERGY PHYSICS
Authors: White Bebo
Published: July 2002

▪ Abstract  High-energy physics and the World Wide Web (WWW) share a rich history. The Web, developed at CERN as a collaboration tool and quickly adopted by the Internet community, has become a communications phenomenon. This article reviews early WWW development and its basic technology. I also summarize some significant applications of Web technology, past and present, and discuss prospects for future use.
ELECTROWEAK STUDIES AT Z FACTORIES
Authors: Hagiwara Kaoru
Published: July 2002

▪ Abstract  The Large Electron Positron collider LEP1 at CERN produced tens of millions of Z bosons, and the e+e− linear collider SLC at SLAC has produced Z bosons with its polarized e− beam. Along with the measurements of the top-quark and W-boson masses at the Fermilab Tevatron [Formula: see text] collider, these Z-factory experiments have tested the standard electroweak theory with unprecedented precision. This chapter reviews the renormalizable gauge theory of the electroweak interactions and its quantum-level tests. Implications of the precision measurements are then studied within the standard model and its extentions.
Precision Measurements of the W Boson Mass
Authors: Glenzinski Douglas A. , Heintz Ulrich
Published: July 2002

▪ Abstract  The standard model of electroweak interactions has had great success in describing the observed data over the past three decades. The precision of experimental measurements affords tests of the standard model at the quantum loop level beyond leading order. Despite this success, it is important to continue confronting experimental measurements with the standard model's predictions because any deviation would signal new physics. As a fundamental parameter of the standard model, the mass of the W boson, MW, is of particular importance. Aside from being an important test of the model itself, a precision measurement of MW can be used to constrain the mass of the Higgs boson, MH. In this article, we review the principal experimental techniques for determining MW and discuss their combination into a single precision MW measurement. We conclude by briefly discussing future prospects for precision measurements of the W boson mass.
METHYLATION PHARMACOGENETICS: Catechol O-Methyltransferase, Thiopurine Methyltransferase, and Histamine N-Methyltransferase
Authors: Weinshilboum Richard M. , Otterness Diane M. , Szumlanski Carol L.
Published: July 2002

▪ Abstract  Methyl conjugation is an important pathway in the biotransformation of many exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. In recent years, characterization of these genetic polymorphisms has been extended to include the cloning of cDNAs and genes, as well as a determination of the molecular basis for the effects of inheritance on these methyltransferase enzymes. The thiopurine methyltransferase genetic polymorphism is responsible for clinically significant individual variations in the toxicity and therapeutic efficacy of thiopurine drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase genetic polymorphism represents one of the first examples in which testing for a pharmacogenetic variant has entered standard clinical practice. The full functional implications of pharmacogenetic variation in the activities of catechol O-methyltransferase and histamine N-methyltransferase remain to be determined. Finally, experimental strategies used to study methylation pharmacogenetics illustrate the rapid evolution of biochemical, pharmacologic, molecular, and genomic approaches that have been used to determine the role of inheritance in variation in drug metabolism, effect, and toxicity.
The Role of Rho in G Protein-Coupled Receptor Signal Transduction
Authors: Sah Valerie P. , Seasholtz Tammy M. , Sagi Sarah A. , Brown Joan Heller
Published: July 2002

Low molecular weight G proteins of the Rho subfamily are regulators of actin cytoskeletal organization. In contrast to the heterotrimeric G proteins, the small GTPases are not directly activated through ligand binding to G protein–coupled receptors (GPCRs). However, a subset of GPCRs, including those for lysophosphatidic acid and thrombin, induce stress fibers, focal adhesions, and cell rounding through Rho-dependent pathways. C3 exoenzyme has been a useful tool for demonstrating Rho involvement in these and other responses, including Ca2+sensitization of smooth muscle contraction, cell migration, transformation, and serum response element–mediated gene expression. Most of the GPCRs that induce Rho-dependent responses can activate Gq, but this is not a sufficient signal. Recent data demonstrate that Gα12/13can induce Rho-dependent responses. Furthermore, Gα12/13can bind and activate Rho-specific guanine nucleotide exchange factors, providing a mechanism by which GPCRs that couple to Gα12/13could activate Rho and its downstream responses.
ON THE CHARACTERISTICS OF MIGRATION OF OLIGOMERIC DNA IN POLYACRYLAMIDE GELS AND IN FREE SOLUTION
Authors: Mohanty Udayan , McLaughlin Larry
Published: July 2002

▪ Abstract  We review a model for the free-solution electrophoretic mobility of oligomeric double-stranded (ds) DNA. We have found that the free-solution mobility of ds DNA increases as the molecular weight of the fragment increases, up to a few hundred base pairs. This insight is combined with recent advances in the nature of counterion condensation theory of very short DNA fragments to describe quantitatively the electrophoretic mobility of oligomeric single-stranded DNA in polyacrylamide gels. The model predicts, in agreement with recent experiments, that significant anomalous migration exists with short DNA sequences, the onset of which is dependent on the size of polyacrylamide gel pores. For terminal phosphate-labeled DNA fragments, the free-solution mobility is no longer proportional to the ratio of the total effective charge and the friction coefficient. These changes in properties affect the characteristics of migration of end-labeled DNA fragments in polyacrylamide gels.
THE LUTEINIZING HORMONE RECEPTOR
Authors: Dufau Maria L.
Published: July 2002

▪ Abstract  The luteinizing hormone receptor (LHR) is a member of the subfamily of glycoprotein hormone receptors within the superfamily of G protein–coupled receptor (GPCR)/seven-transmembrane domain receptors. Over the past eight years, major advances have been made in determining the structure and function of the LHR and its gene. The hormone-binding domain has been localized to exons 1–7 in the extracellular (EC) domain/region of the receptor, which contains several leucine-rich repeats. High-affinity binding of LH and human chorionic gonadotropin (hCG) causes secondary hormone or receptor contacts to be established with regions of the EC loop/transmembrane module that initiate signal transduction.

Models of hormone-receptor interaction have been derived from the crystal structures of hCG and of the ribonuclease inhibitor, which also contains leucine-rich repeats. Such models provide a framework for the interpretation of mutational studies and for further experiments. The extracellular domain of the receptor has been overexpressed in vitro, which will facilitate crystallographic resolution of the structure of the receptor-binding site. The transmembrane domain/loop/cytoplasmic module transduces the signal for couplingto G proteins.

Several constitutive, activating mutations that cause human disease have been found in helix VI and adjacent structures. These mutations have provided valuable information about mechanisms of signal transfer and G protein coupling. The structure of the LHR gene has been elucidated, and the regulation of its transcription is beginning to be understood. Valuable insights into receptor evolution have been derived from analysis of sequence homologies, the gene structure of glycoprotein hormone receptors and other members of the GPCR family, and the glycoprotein hormone receptor–like precursors identified in several invertebrate species.
SEX IN THE 90s:SRYand the Switch to the Male Pathway
Authors: Capel Blanche
Published: July 2002

▪ Abstract  In mammals the male sex determination switch is controlled by a single gene on the Y chromosome, SRY. SRY encodes a protein with an HMG-like DNA-binding domain, which probably acts as a local organizer of chromatin structure. It is believed to regulate downstream genes in the sex determination cascade, although no direct targets of SRY are clearly known. More genes in the pathway have been isolated through mutation approaches in mouse and human. At least three genes, SRY itself, SOX9, and DAX1, are dosage sensitive, providing molecular evidence that the sex determination step operates at a critical threshold. SRY initiates development of a testis from the bipotential cells of the early gonad. The dimorphic male and female pathways present a rare opportunity to link a pivotal gene in development with morphogenetic mechanisms that operate to pattern an organ and the differentiation of its cells. Mechanisms of testis organogenesis triggered downstream of SRY include pathways of cell signaling controlling cell reorganization, cell proliferation, cell migration, and vascularization.
Molecular Regulation of Lung Development
Authors: Cardoso Wellington V
Published: July 2002

▪ Abstract  There is increasing evidence suggesting that formation of the tracheobronchial tree and alveoli results from heterogeneity of the epithelial-mesenchymal interactions along the developing respiratory tract. Recent genetic data support this idea and show that this heterogeneity is likely the result of activation of distinct networks of signaling molecules along the proximal-distal axis. Among these signals, fibroblast growth factors, retinoids, Sonic hedgehog, and transforming growth factors appear to play prominent roles. We discuss how these and other pattern regulators may be involved in initiation, branching, and differentiation of the respiratory system.
G Protein–Coupled Prostanoid Receptors and the Kidney
Authors: Breyer Matthew D , Breyer Richard M
Published: July 2002

▪ Abstract  Renal cyclooxygenase 1 and 2 activity produces five primary prostanoids: prostaglandin E2, prostaglandin F2α, prostaglandin I2, thromboxane A2, and prostaglandin D2. These lipid mediators interact with a family of distinct G protein-coupled prostanoid receptors designated EP, FP, IP, TP, and DP, respectively, which exert important regulatory effects on renal function. The intrarenal distribution of these prostanoid receptors has been mapped, and the consequences of their activation have been partially characterized. FP, TP, and EP1receptors preferentially couple to an increase in cell calcium. EP2, EP4, DP, and IP receptors stimulate cyclic AMP, whereas the EP3receptor preferentially couples to Gi, inhibiting cyclic AMP generation. EP1and EP3mRNA expression predominates in the collecting duct and thick limb, respectively, where their stimulation reduces NaCl and water absorption, promoting natriuresis and diuresis. The FP receptor is highly expressed in the distal convoluted tubule, where it may have a distinct effect on renal salt transport. Although only low levels of EP2receptor mRNA are detected in the kidney and its precise intrarenal localization is uncertain, mice with targeted disruption of the EP2receptor exhibit salt-sensitive hypertension, suggesting that this receptor may also play an important role in salt excretion. In contrast, EP4receptor mRNA is predominantly expressed in the glomerulus, where it may contribute to the regulation of glomerular hemodynamics and renin release. The IP receptor mRNA is highly expressed near the glomerulus, in the afferent arteriole, where it may also dilate renal arterioles and stimulate renin release. Conversely, TP receptors in the glomerulus may counteract the effects of these dilator prostanoids and increase glomerular resistance. At present there is little evidence for DP receptor expression in the kidney. These receptors act in a concerted fashion as physiological buffers, protecting the kidney from excessive functional changes during periods of physiological stress. Nonsteroidal anti-inflammatory drug (NSAID)-mediated cyclooxygenase inhibition results in the loss of these combined effects, which contributes to their renal effects. Selective prostanoid receptor antagonists may provide new therapeutic approaches for specific disease states.
Molecular Components of the Circadian System in Drosophila
Authors: Williams Julie A , Sehgal Amita
Published: July 2002

▪ Abstract  Much of our current understanding of how circadian rhythms are generated is based on work done with Drosophila melanogaster. Molecular mechanisms used to assemble an endogenous clock in this organism are now known to underlie circadian rhythms in many other species, including mammals. The genetic amenability of Drosophila has led to the identification of some genes that encode components of the clock (so-called clock genes) and others that either link the clock to the environment or act downstream of it. The clock provides time-of-day cues by regulating levels of specific gene products such that they oscillate with a circadian rhythm. The mechanisms that synchronize these oscillations to light are understood to some extent. However, there are still large gaps in our knowledge, in particular with respect to the mechanisms used by the clock to control overt rhythms. It has, however, become clear that in addition to the brain clock, autonomous or semi-autonomous clocks occur in peripheral tissues where they confer circadian regulation on specific functions.
G Proteins and Pheromone Signaling
Authors: Dohlman Henrik G.
Published: July 2002

▪ Abstract  All cells have the capacity to respond to chemical and sensory stimuli. Central to many such signaling pathways is the heterotrimeric G protein, which transmits a signal from cell surface receptors to intracellular effectors. Recent studies using the yeast Saccharomyces cerevisiae have produced important advances in our understanding of G protein activation and inactivation. This review focuses on the mechanisms by which G proteins transmit a signal from peptide pheromone receptors to the mating response in yeast and how mechanisms elucidated in yeast can provide insights to signaling events in more complex organisms.
PLANT PATHOLOGY: A Discipline at a Crossroads
Authors: Weinhold Albert R.
Published: July 2002

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▪ Abstract  The Department of Plant Pathology at the University of California at Berkeley was destroyed as a consequence of a contentious reorganization. The circumstances that led to the reorganization provide some insight into the challenges facing the discipline of plant pathology. The underlying basis for plant pathology as a science is to address problems of plant disease. This requires a balance between disciplinary and problem-solving research and a continuum from achieving fundamental advances in knowledge to the development and implementation of problem-solving approaches. Changes in colleges and universities have placed extreme stress on this essential structure. The dilemma that must be addressed is how to reestablish the problem-solving continuum where it has been broken and strengthen it where it has been weakened. Plants are essential for life, and they will always be affected by disease. The understanding and management of these diseases is the responsibility and the challenge of plant pathology today and in the future.
PHILIP HERRIES GREGORY 1907–1986: Pioneer Aerobiologist, Versatile Mycologist
Authors: Lacey John , Lacey Maureen E. , Fitt Bruce D. L.
Published: July 2002

[Figure: see text]

▪ Abstract  Philip Gregory pioneered aerobiology as a topic for research, drawing together inputs from many disciplines to contribute to better understanding of fungal spore dispersal, plant disease epidemiology, and allergy. In childhood, he was interested in natural history and meteorology and frequently suffered from asthma. Initially, he worked with dermatophytes in Winnipeg, where he was influenced by Buller. Returning to Britain, he investigated the epidemiology first of flower bulb diseases and then of potato virus diseases, noting the occurrence of disease gradients in crops. He developed theories of spore dispersal during wartime air-raid duties and published these in his classic paper of 1945. The remainder of his career was largely spent obtaining data in support of his theories of spore dispersal and disease gradients, on understanding splash dispersal, in identifying the cause of farmer's lung disease, and in his retirement, in elucidating the epidemiology of black pod disease of cocoa in Nigeria.
BEVERLY T. GALLOWAY: Visionary Administrator
Authors: Peterson Jr Paul D. , Campbell C. Lee
Published: July 2002

[Figure: see text]

▪ Abstract  With a career that began at the University of Missouri in the early 1880s and culminated at the USDA in the 1930s, Beverly Galloway devoted his life to practical botany and agriculture. He became a driving force in the movement for “New Botany” during a period that stressed an experimental approach as well as new disciplines such as plant pathology. As administrator and scientist, he was arguably the single, most influential figure involved in the early growth and development of plant pathology and the plant sciences generally in the USDA. From assistant mycologist in the Section of Mycology to Chief of the Bureau of Plant Industry to Assistant Secretary of the USDA, Galloway displayed exceptional administrative acumen. His administrative and scientific skills were instrumental in laying the foundations for the science of plant pathology during its formative period in the United States.
Rhizosphere Interactions and the Exploitation of Microbial Agents for the Biological Control of Plant-Parasitic Nematodes
Authors: Kerry B. R.
Published: July 2002

A range of specialist and generalist microorganisms in the rhizosphere attacks plant-parasitic nematodes. Plants have a profound effect on the impact of this microflora on the regulation of nematode populations by influencing both the dynamics of the nematode host and the structure and dynamics of the community of antagonists and parasites in the rhizosphere. In general, those organisms that have a saprophytic phase in their life cycle are most affected by environmental conditions in the rhizosphere, but effects on obligate parasites have also been recorded. Although nematodes influence the colonization of roots by pathogenic and beneficial microorganisms, little is known of such interactions with the natural enemies of nematodes in the rhizosphere. As nematodes influence the quantity and quality of root exudates, they are likely to affect the physiology of those microorganisms in the rhizosphere; such changes may be used as signals for nematode antagonists and parasites. Successful biological control strategies will depend on a thorough understanding of these interactions at the population, organismal, and molecular scale.
SOCIAL CHOICE THEORY, GAME THEORY, AND POSITIVE POLITICAL THEORY
Authors: Austen-Smith David , Banks Jeffrey S.
Published: July 2002

▪ Abstract  We consider the relationships between the collective preference and non-cooperative game theory approaches to positive political theory. In particular, we show that an apparently decisive difference between the two approaches—that in sufficiently complex environments (e.g. high-dimensional choice spaces) direct preference aggregation models are incapable of generating any prediction at all, whereas non-cooperative game-theoretic models almost always generate prediction—is indeed only an apparent difference. More generally, we argue that when modeling collective decisions there is a fundamental tension between insuring existence of well-defined predictions, a criterion of minimal democracy, and general applicability to complex environments; while any two of the three are compatible under either approach, neither collective preference nor non-cooperative game theory can support models that simultaneously satisfy all three desiderata.
How Well Are Hypertension, Hyperlipidemia, Diabetes, and Smoking Managed After a Stroke or Transient Ischemic Attack?
Authors: Mouradian Mikael S. , Majumdar Sumit R. , Senthilselvan Ambikaipakan , Khan Khurshid , Shuaib Ashfaq
Published: July 2002

Background and Purpose

—

Stroke prevention clinics (SPCs) are not usually involved with the active management of hypertension, hyperlipidemia, diabetes, and smoking. The effect of consultations generated at SPCs on the adequacy of the management of these risk factors for stroke has not been well described, and few studies have long-term follow-up.

Methods

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We performed a prospective study of 119 consecutive patients referred to an SPC for secondary prevention. One year after their baseline visit, patients were re-evaluated for the adequacy of the management of the above risk factors, and the proportion of improvement was assessed.

Results

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One-hundred twelve patients returned for their 1-year follow-up visit. Sixty-six were male, and the average age was 65 years. Hypertension was present in 83 patients, hyperlipidemia in 92, diabetes in 26, and smoking in 38, and 80 had multiple risk factors. At baseline, 66% of patients with hypertension, 17% of patients with hyperlipidemia, and 23% of diabetics had adequate management of their respective risk factors. During 1 year of follow-up, hypertension management improved 20% (
P
<0.001) and lipid management improved 32% (
P
<0.001). There was no significant improvement in diabetes management or smoking cessation.

Conclusions

—

Although our understanding of the benefit of addressing hypertension, hyperlipidemia, diabetes, and smoking for secondary prevention of stroke is evolving, we found marked room for improvement in the management of these four risk factors. SPCs may need to be more actively involved in the management of these modifiable risk factors, if we are to significantly impact the risk of recurrent stroke.
The Politics of Speculative Attacks in Industrial Democracies
Authors: Leblang David , Bernhard William
Published: July 2002

Recent models of speculative currency crises contend that market expectations of policy behavior can trigger a speculative attack. We argue that political processes and partisan objectives inform expectations about the government's commitment to the exchange rate. First, market actors anticipate periods when the partisan identity of a government may change through an election or a cabinet collapse. Second, party labels provide information to currency traders about the policy objectives of a potential government. Consequently, we contend that the probability of a speculative attack will be higher when markets expect the cabinet to end and when the cabinet dissolution is likely to produce a leftward shift in policy. A discrete timesurvival model is used to estimate the probability that a cabinet will dissolve in any given month for sixteen parliamentary democracies from 1970 to 1995. The predicted values are then used as a proxy for market expectations in a model of speculative currency crises.
NAFTA and the Legalization of World Politics: A Case Study
Authors: Abbott Frederick M.
Published: July 2002

I examine the trend toward using hard legal instruments in international trade governance and explain this trend in the context of the North American Free Trade Agreement (NAFTA). I suggest that hard law (1) reduces intergovernmental transaction costs, (2) reduces private risk premiums associated with trade and investment, (3) promotes transparency and provides corollary participation benefits, (4) tends to restrain strategic political behaviors, and (5) may increase the range of integration effects by encouraging private actors to enforce intergovernmental obligations. I compare the legalization model of NAFTA with those of the European Union (EU) and the Asia-Pacific Economic Cooperation (APEC) forum.