bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Factors and Therapeutic Decisions in Axillary Node-Negative Breast Cancer
Authors: Elledge Richard M. , McGuire William L.
Published: July 2003

The incidence of node-negative breast cancer is increasing, and it is becoming a more commonly encountered clinical problem. Prognostic factors such as tumor size, histopathological characteristics, receptor status, proliferative markers, biochemical alterations, and gene abnormalities can be useful in assessing the risk of cancer recurrence after primary local therapy. By accurately assessing the risk of recurrence, informed decisions can be made about whether or not to treat with adjuvant systemic therapy.
GENETICS OF CAMPYLOBACTER AND HELICOBACTER
Authors: Taylor Diane E.
Published: July 2003

This article reviews the current state of genetic analysis of Campylobacter and Helicobacter. Chromosomal genes cloned from Campylobacter and Helicobacter species are listed along with the method used to identify the cloned gene. Campylobacter plasmid genes that have been cloned and expressed in Escherichia coli and that specify resistance to tetracycline, kanamycin, or chloramphenicol are presented.

This review also examines our current knowledge of genetic exchange in Campylobacter, including conjugative plasmid transfer, natural transformation, electrotransformation, and bacteriophage transduction. In Helicobacter, natural transformation has been described and both plasmids and bacteriophages have been observed. Plasmid cloning vectors have been constructed for Campylobacter. Available vectors are discussed and restriction maps of some useful vectors that we have constructed are included.

The genome sizes of C. jejuni and C. coli are approximately 1.7 megabases (Mb), whereas the genome size of H. pylori ranges from l.60 to l.73 Mb. The positions of various genes on the C. jejuni and C. coli genome maps have been determined using both homologous and heterologous DNA probes. Genomic maps of these organisms are presented.
REFLECTIONS OF A MICROBIOLOGIST, OR HOW TO LEARN FROM THE MICROBES
Authors: Pfennig Norbert
Published: July 2003

This autobiographical chapter summarizes the author's work with a defined mineral medium for fastidious sulfide-oxidizing phototrophic purple and green sulfur bacteria that were known already from Winogradsky's and Lauterborn's descriptions. The pure cultures, isolated from natural mud deposits, revealed interesting new cytological and biochemical features. In the wake of these studies, new anaerobic bacteria with unusual metabolic capacities were isolated and characterized. Ecologically most significant is the dehydrogenation of acetate to carbon dioxide. Electron acceptors are sulfur for the sulfur reducers and sulfate for the new sulfate reducers obtained by Widdel. Thauer and Fuchs showed that a modified TCA-cycle and the new acetyl-CoA:carbon monoxide dehydrogenase pathway operates in the oxidation of acetate. Many aliphatic and aromatic compounds were shown to be completely degradable by marine sulfate reducers. The biogeochemical transformations of the anoxic sulfur cycle are now understood in terms of the capacities of the phototrophic and chemotrophic bacterial species involved in the cycle.
AGROACTIVE COMPOUNDS OF MICROBIAL ORIGIN
Authors: Tanaka Yoshitake , Omura Satoshi
Published: July 2003

Microbial metabolites attract increasing attention as potential pesticides. They are expected to overcome the resistance and pollution that have accompanied the use of synthetic pesticides. Several microbial metabolites, such as avermectin, have proved useful as agroactive agents. In this review, we attempt to identify newer agroactive microbial metabolites with feasible activity or interesting action sites from those reported in recent years. In addition, microbial and chemical modifications of existing microbial agrochemicals are discussed to illustrate the usefulness of these technologies in potentiating agroactivity and stability. We discuss the possibility of future discovery of excellent microbial agrochemicals, and the importance of efforts to promote positive public perception and public acceptance of pesticide chemicals.
A CHARMED LIFE
Authors: Magasanik Boris
Published: July 2003

Boris Magasanik was born in Kharkoff, Ukraine, on December 19, 1919. He received his preliminary and secondary education in Vienna, Austria, and studied chemistry at the University of Vienna in 1937. He continued his studies at City College, New York (BS, 1941) and after one semester of graduate study at Pennsylvania Stale University, served in the US Army in England and France from 1942-1945. He obtained his PhD degree in biochemistry from Columbia University in 1948. A faculty member in the Department of Bacteriology and Immunology at Harvard Medical School from 1951 to 1960, he then continued his career as Professor of Microbiology at MIT where he served as head of the Department from 1967 to 1977. He became a member of the National Academy of Sciences USA in 1969 and received the Selman A Waksman Award in 1993. He is currently the Jacques Monod Professor Emeritus at MIT and is the author of over 240 publications dealing with microbial physiology and the regulation of gene expression in bacteria and yeast.
Trinucleotide Repeats in Neurogenetic Disorders
Authors: Paulson H. L. , Fischbeck K. H.
Published: July 2003

Trinucleotide repeat expansion is increasingly recognized as a cause of neurogenetic diseases. To date, seven diseases have been identified as expanded repeat disorders: the fragile X syndrome of mental retardation (both FRAXA and FRAXE loci), myotonic dystrophy, X-linked spinal and bulbar muscular atrophy, Huntington’s disease, spinocerebellar ataxia type 1, dentatorubral-pallidoluysian atrophy, and Machado-Joseph disease. All are neurologic disorders, affecting one or more regions of the neuraxis. Moreover, five of the seven (the last five above) are progressive neurodegenerative disorders whose strikingly similar mutations suggest a common mechanism of neuronal degeneration. In this article we discuss specific characteristics of each trinucleotide repeat disease, review their shared clinical and genetic features, and address possible molecular mechanisms underlying the neuropathology in each disease. Particular attention is paid to the neurodegenerative diseases, all of which are caused by CAG repeats encoding polyglutamine tracts in the disease gene protein.
Inferotemporal Cortex and Object Vision
Authors: Tanaka Keiji
Published: July 2003

Cells in area TE of the inferotemporal cortex of the monkey brain selectively respond to various moderately complex object features, and those that cluster in a columnar region that runs perpendicular to the cortical surface respond to similar features. Although cells within a column respond to similar features, their selectivity is not necessarily identical. The data of optical imaging in TE have suggested that the borders between neighboring columns are not discrete; a continuous mapping of complex feature space within a larger region contains several partially overlapped columns. This continuous mapping may be used for various computations, such as production of the image of the object at different viewing angles, illumination conditions. and articulation poses.
COLORVISION
Authors: Gegenfurtner Karl R. , Kiper Daniel C.
Published: July 2003

▪ Abstract  Color vision starts with the absorption of light in the retinal cone photoreceptors, which transduce electromagnetic energy into electrical voltages. These voltages are transformed into action potentials by a complicated network of cells in the retina. The information is sent to the visual cortex via the lateral geniculate nucleus (LGN) in three separate color-opponent channels that have been characterized psychophysically, physiologically, and computationally. The properties of cells in the retina and LGN account for a surprisingly large body of psychophysical literature. This suggests that several fundamental computations involved in color perception occur at early levels of processing. In the cortex, information from the three retino-geniculate channels is combined to enable perception of a large variety of different hues. Furthermore, recent evidence suggests that color analysis and coding cannot be separated from the analysis and coding of other visual attributes such as form and motion. Though there are some brain areas that are more sensitive to color than others, color vision emerges through the combined activity of neurons in many different areas.
EPIDEMIOLOGY OFNEURODEGENERATION
Authors: Mayeux Richard
Published: July 2003

▪ Abstract  Alzheimer's disease, Parkinson's disease, and motor neuron disease share a propensity to occur with increasing age and as either a sporadic or a familial disorder. A number of behavioral and environmental risk factors have been proposed for each disorder, but most associations lack consistency and specificity. Over the last decade the remarkable frequency of these disorders has become apparent, and the identification of mutations in genes has provided the means to understand their pathogenesis. Better and more accurate means to characterize and diagnose these diseases has greatly facilitated analytic epidemiology. The analysis of behavioral and genetic factors that may lower disease risk has led to clinical trials that are either in progress or being planned with the aim of preventing these disorders.
Advances in Polarized Electron Sources
Authors: Prepost R. , Maruyama T.
Published: July 2003

In this chapter, we review recent advances in the technology of polarized electron sources. Significant electron-spin polarization above 50% has been achieved with new photocathode structures based on the conventional GaAs photoemitter. Since 1991, significant enhancements of polarization utilizing strained heterostructures and GaAs-A1GaAs superlattices have been reported. We discuss the basic theoretical background and the techniques required to build such strained structures in detail. The operational performance of strained GaAs cathodes now in use at the Stanford Linear Accelerator Center (SLAC) for colliding-beam and fixed-target experiments is reviewed as well.
Regulation of Tight-Junction Permeability During Nutrient Absorption Across the Intestinal Epithelium
Authors: Ballard Stephen T. , Hunter James H. , Taylor Aubrey E.
Published: July 2003

Tight junctions are located at the luminal aspect of adjacent epithelial cells and form a barrier that limits the paracellular diffusion of hydrophilic solutes. In recent years, evidence has accumulated to indicate that tight-junction permeability is regulated by the absorption of various nutrients. In this review, we present the physiological basis and importance of tight-junction regulation in intestinal epithelium. The molecular structure of tight junctions and their interactions with the cell cytoskeleton as well as the physical and chemical forces that influence tight junction permeability are described. Much of this review addresses the controversial Pappenheimer hypothesis, which states that a major portion of intestinal glucose absorption occurs through tight junctions and not by saturable transcellular active transport. The absorption of a significant portion of glucose through tight junctions requires increased junctional permeability, a very high intralumenal glucose concentration, and a sufficient osmotic gradient to promote volume flow.
Retinoids as Teratogens
Authors: Soprano Dianne Robert , Soprano Kenneth J.
Published: July 2003

Vitamin A is a necessary nutrient in the diet. However, excessive doses of retinoids by pregnant women result in teratogenesis. In this chapter, we initially discuss the occurrence and characteristics of fetal malformations associated with maternal ingestion of natural and synthetic retinoids in both experimental animals and humans. We then tum to an examination of the pharmacology of teratogenic retinoids, focusing on structure-function relationships and pharmacokinetics. Finally, we review the current literature on the molecular mechanism of action of teratogenic doses of retinoids and the role of the retinoic acid receptors and other target genes in this process.
Regulation of Glutaminase Activity and Glutamine Metabolism
Authors: Curthoys Norman P. , Watford Malcolm
Published: July 2003

Glutamine is synthesized primarily in skeletal muscle, lungs, and adipose tissue. Plasma glutamine plays an important role as a carrier of nitrogen, carbon, and energy between organs and is used for hepatic urea synthesis, for renal ammoniagenesis, for gluconeogenesis in both liver and kidney, and as a major respiratory fuel for many cells. The catabolism of glutamine is initiated by either of two isoforms of the mitochondrial glutaminase. Liver-type glutaminase is expressed only in periportal hepatocytes of the postnatal liver, where it effectively couples ammonia production with urea synthesis. Kidney­type glutaminase is abundant in kidney, brain, intestine, fetal liver, lymphocytes, and transformed cells, where the resulting ammonia is released without further metabolism. The two isoenzymes have different structural and kinetic properties that contribute to their function and short-term regulation. Although there is a high degree of identity in amino acid sequences, the two glutaminases are the products of different but related genes. The two isoenzymes are also subject to long-term regulation. Hepatic glutaminase is increased during starvation, diabetes, and feeding a high-protein diet, whereas kidney-type glutaminase is increased only in kidney in response to metabolic acidosis. The adaptations in hepatic glutaminase are mediated by changes in the rate of transcription, whereas kidney-type glutaminase is regulated at a posttranscriptional level.
Nutritional and Hormonal Regulation of Thyroid Hormone Deiodinases
Authors: Larsen P. R. , Berry M. J.
Published: July 2003

Selenocysteine has been identified in the active center of types 1 and 3 iodothyronine deiodinases, two important enzymes regulating the formation and degradation of the active thyroid hormone, 3,5,3′-triiodothyronine (T3). Selenium is thus required for such complex processes as normal growth, brain development, and metamorphosis, all of which are thyroid hormone dependent. Structural and functional analyses of the type 1 deiodinase mRNA allowed identification of the selenocysteine insertion sequence (SECIS) element, a stem-loop structure in the 3′ untranslated region of the mRNA. SECIS elements with conserved sequence and structural features are also present in the 3′ untranslated regions of the mRNAs encoding selenoprotein P and the glutathione peroxidase family of selenoproteins. These elements are necessary and sufficient for directing selenocysteine incorporation into the deiodinases and the other mammalian selenoproteins.
Antioxidants in Human Health and Disease
Authors: Halliwell Barry
Published: July 2003

Free radicals and antioxidants are widely discussed in the clinical and nutritional literature. Antioxidants are needed to prevent the formation and oppose the actions of reactive oxygen and nitrogen species, which are generated in vivo and cause damage to DNA, lipids, proteins, and other biomolecules. Endogenous antioxidant defenses (superoxide dismutases, H2O2-removing enzymes, metal binding proteins) are inadequate to prevent damage completely, so dietderived antioxidants are important in maintaining health. Many dietary compounds have been suggested to be important antioxidants: The evidence for a key role of vitamins E and C is strong, but that for carotenoids and related plant pigments is weaker. Interest is also growing in the role of plant phenolics, especially flavonoids. Some antioxidants can exert prooxidant effects in vitro, but their physiological relevance is uncertain. Experimental approaches to the optimization of antioxidant nutrient intake are proposed.
Oxidized Low Density Lipoproteins in Atherogenesis: Role of Dietary Modification
Authors: Reaven Peter D. , Witztum Joseph L.
Published: July 2003

The development of atherosclerosis is a complex and multistep process. There are many determinants in the pathogenesis of this condition, with different factors presumably playing key roles at different times in the evolution of the atherosclerotic plaque. It has been suggested that oxidation of low density lipoproteins (LDL) by cells in the artery wall leads to a proatherogenic particle that may help initiate early lesion formation. For this reason, understanding the determinants of LDL susceptibility to oxidation is essential for developing therapeutic strategies to inhibit this process. Oxidation of LDL begins with the abstraction of hydrogen from polyunsaturated fatty acids; thus, LDL fatty acid composition undoubtedly contributes to the process of LDL oxidation. Since dietary fatty acids influence the fatty acid composition of LDL and cell membranes, the amount and type of fat in the diet may effect susceptibility of LDL and cells to oxidative damage. Additionally, since cell membrane fatty acid composition also influences cellular formation of reactive oxygen species, dietary fatty acids may help determine the prooxidant activity of artery wall cells. Both cells and lipoproteins contain a variety of antioxidants that provide protection against oxidative stress. A major source of these antioxidants is the diet. Enrichment of the diet with foods high in such antioxidants as vitamin E, β-carotene. or vitamin C, or supplementation of the diet with antioxidant vitamins, may inhibit oxidation and the process of atherosclerosis.
Peptide Transporters in the Intestine and the Kidney
Authors: Leibach Frederick H. , Ganapathy Vadivel
Published: July 2003

Even though the existence of a transport process for intact peptides in the brush border membrane of intestinal and renal absorptive epithelial cells has been known for almost three decades, it is only recently that the molecular nature of the proteins responsible for the transport process has been elucidated. Two peptide transporters, PEW 1 and PEPT 2, have been cloned. The cloned transporters catalyze active transport of intact di- and tripeptides and utilize a transmembrane electrochemical H+ gradient as the driving force. The characteristic of H+ coupling makes PEPT 1 and PEPT 2 unique among the transporters thus far identified in mammalian cells. In addition, the peptide transporters have immediate pharmacologic relevance because a number of peptide-like drugs are recognized as substrates by these transporters. Recently, cultured cell lines of intestinal and renal origin that express PEPT 1 and PEPT 2 have been identified. These cell lines are likely to facilitate studies on the regulatory aspects of the peptide transporters.
Regulation of Carbohydrate and Fat Metabolism During and After Exercise
Authors: Holloszy John O. , Kohrt Wendy M.
Published: July 2003

During vigorous exercise, carbohydrate, in the form of muscle glycogen and blood glucose, is the primary energy source, whereas fatty acids play a secondary, carbohydrate-sparing role. In the postabsorptive state, nearly all of the carbohydrate used during exercise comes from muscle and liver glycogen. The size of these glycogen stores plays a major role in determining how long vigorous endurance exercise can be performed if other causes of fatigue, such as dehydration or heat exhaustion, are avoided. In a “fight or flight” situation, individuals whose muscles are glycogen depleted are helpless, as they are unable to either run or fight. The same is true of someone who has become markedly hypoglycemic as a result of liver glycogen depletion.
Factors Influencing Disease Expression in Hemochromatosis
Authors: Crawford Darrell H. G. , Powell Lawrie W. , Halliday June W. , Leggett Barbara A.
Published: July 2003

Genetic hemochromatosis is one of the most common inherited disorders in Caucasian populations. The disease frequency in Caucasian populations in Australia, Europe, and the United States is 1:300-400. The basic genetic defect remains unknown, although the hemochromatosis gene is closely linked to histocompatibility antigen (HLA) A, thus allowing early diagnosis in members of affected families. Many factors—environmental, genetic, and nongenetic in nature—influence the degree of iron loading in affected individuals. In particular, pathologic and physiologic blood loss and blood donation influence iron stores in hemochromatosis. The iron concentration in the liver is an important determinant of survival because a hepatic iron concentration in excess of 400 pmol/g dry weight is usually associated with cirrhosis. Patients with cirrhosis secondary to hemochromatosis are at risk of heptocellular carcinoma and complications of portal hypertension. The combination of improved awareness of the condition and the use of HLA typing to identify affected family members has led to earlier diagnosis and therapy, and to an improvement in overall survival
Effects of Food on Drug Absorption
Authors: Welling Peter G.
Published: July 2003

This chapter provides an update on drug-food interactions reported in the literature during the past five years. The number of studies examining this phenomenon has increased dramatically, and many of the results of these studies have been unpredictable and spectacular. Drug-food interactions should really be considered as formulation-food interactions because of increasing evidence that a drug may be affected differently by food when it is administered in different formulations. Drug-food interactions may be classified into five categories: those causing reduced, delayed, increased, and accelerated absorption, and those in which food has no effect. While it continues to be necessary to examine drugfood interactions for specific drugs and drug formulations, additional avenues need to be explored to seek mechanistic patterns that may lead to better prediction of the nature and extent of changes in circulating drug levels due to the presense of food, and their possible clinical impact.
Cutaneous Pharmacology and Toxicology
Authors: Maibach Howard
Published: July 2003

The fields of cutaneous pharmacology and toxicology existed as long as man used topical therapy; some medicaments were helpful and others harmful. This review documents recent progress in these fields in terms of the experimental method. Emphasis has been given to conceptual and methodologic progress rather than a list of new molecules. As signs of the advent of the maturity of these fields, a graduate school course has recently been completed, one text has been published (7), and at least two are in preparation. It is likely that the next review of this topic in this series will reflect this considerable progress in terms of relevance to man.
Some Spectroscopic Reminiscences
Authors: Klemperer William
Published: July 2003

We review a number of essentially spectroscopic problems in this personal account. The structure of high-temperature species remains a topic of considerable broad interest. The binary fluorides of essentially every element are stable as the isolated gas-phase molecular species. As such they provide a means of comparing bonding with the entire periodic table. The structural characterization of the binary fluorides, although still incomplete, has provided a considerable insight into a variety of bonding types.

The formation of molecules in the interstellar medium has been a model for abiotic synthesis of complex species. A kinetic model based upon ion­molecule reactions as the predominant reaction class appears to fit many of the observations, such as the polyatomic ion HCO+. The high abundance of carbon-chain compounds is attributed to the efficient formation of C+ by the reaction CO+He+ →C+ +O+He.

The spectroscopic characterization of weakly bonded species has led to a detailed knowledge of intermolecular potentials. The dynamics of molecular complexes has been frequently novel. In particular the concurrent breaking and making of weak bonds is observed in many species
Dynamics and Photochemistry of Neutral van der Waals Clusters
Authors: Bernstein Elliot R.
Published: July 2003

This review covers the field of excited electronic-state chemical reactions in small clusters. The clusters emphasized are those comprised of an organic chromophore that is electronically excited to initiate the reaction and of various coreactant molecules ranging from water and ammonia to ethers, amines, aromatics, alkanes, alkenes, and diatomics. The reactions discussed include vibrational relaxation, vibrational predissociation, electron transfer, proton transfer, and radical additions. The reactions are analyzed based on laser-induced fluorescence excitation, dispersed emission, mass-resolved excitation spectroscopy, stimulated emission pumping, and picosecond time-resolved implementation of these spectroscopies.
Time-Dependent Wave Packet Approach to Quantum Reactive Scattering
Authors: Jackson Bret
Published: July 2003

The use of wave packets in time-dependent quantum mechanical studies of chemical reaction dynamics is examined. The basic priniciples of time­dependent scattering theory are reviewed. The Fourier-grid method and various propagation schemes are discussed. A number of useful methodologies are examined, such as discrete variable representations and close­coupling expansions, multiconfiguration self-consistent field formulations, and the mixing of classical with quantum variables. Numerous applications to gas-surface scattering are considered. The dissociative adsorption of diatomic molecules on metal surfaces and the Eley-Rideal recombination of gas-phase atoms with atoms adsorbed on surfaces are discussed in detail. Applications to gas-phase reactions are also examined, with emphasis on three-body A+BC and four-body AB+CD reactions.
External Infrared Reflection Absorption Spectrometry of Monolayer Films at the Air-Water Interface
Authors: Mendelsohn Richard , Brauner Joseph W. , Gericke Arne
Published: July 2003

The theory and practice of external infrared reflection absorption spectrometry (IRRAS) as applied to monomolecular films at the air-water interface are reviewed. The observed IR frequencies for films of amphiphilic species provide information about the conformational states of the hydrocarbon chains and the hydrogen bonding and ionization states of the polar head groups, under conditions of controlled surface pressure. Determination of molecular orientation is also feasible and requires detailed consideration of the reflection-absorption properties of the three­ phase (air-monolayer-water) system. Current theoretical approaches are described.

Applications of IRRAS to the study of single- and double-chain amphiphiles and proteins are reviewed, and initial excursions into biochemistry (interfacial enzyme catalysis) and physiology (pulmonary surfactant function) are reported.
Potential Energy Surfaces for Chemical Reactions at Solid Surfaces
Authors: Garrison Barbara J , Srivastava Deepak
Published: July 2003

Many-body potential energy surfaces (PESs) for describing atomic interactions in gas-solid and surface reaction dynamics are reviewed in this work. Initial PESs from the 1960s-1970s were restricted to a diatomic molecule interacting with a solid surface. Since the 1980s, a multitude of many-body reactive PESs, their parameterization, and their applications have been reported in the literature. Although we mention most of the PESs in general, we have chosen to describe only those that either have had general utility or have had staying power, i.e. they have been used widely by other research groups. The potentials discussed in the most detail are the Stillinger-Weber and Tersoff Si PESs, the Brenner hydrocarbon PES, and the embedded-atom method (EAM) style potentials for metals. We conclude that although these PESs have been used successfully in large-scale computer simulations, further development is needed in many-body PESs. In particular, the development of new functional forms for multicomponent reactive systems is required.
Femtosecond Pulse Shaping, Multiple-Pulse Spectroscopy, and Optical Control
Authors: Kawashima Hitoshi , Wefers Marc M. , Nelson Keith A.
Published: July 2003

A review is presented of femtosecond pulse-shaping methods and their application to spectroscopy of atoms, molecules, and condensed materials. Pulse shaping can be used to generate femtosecond pulse sequences and other optical waveforms whose time-dependent amplitude, phase, frequency, and polarization profiles are all specified precisely. The light­matter interaction mechanisms through which such waveforms can be used for optical control over molecular and material responses are discussed. Most of the spectroscopic experiments conducted to date that involve shaped femtosecond waveforms are reviewed. These have involved control over coherent electronic responses of atoms, small molecules, and multiple quantum wells and control over coherent molecular and lattice vibrations. A selective review is presented of theoretical predictions and qualitative discussions of optical control possibilities involving complex ultrafast waveforms
Rhapsody in Science
Authors: Scholander P. F.
Published: July 2003

Dear readers, I find it quite shocking to have reached a stage in life when I am supposed to be retrospective. Like a vulgar streaker I shall expose myself in the limelight. I frequently ask myself how has it been possible to live such an exciting and happy life being such an irregular and irresponsible person?

My Norwegian mother was an accomplished pianist. I have just noticed in her copy of Speemans' encyclopedia, Goldenes Buch der Musik (1909), that she underlined the following advice to prospective musicians (which in my opinion applies to scientists as well): “Only such a person can I advise to become an artist, who from pure love of art itself, through internal urge and need—unconcerned about spectacular successes—desires to devote his life to it and therein to find his fulfillment and his happiness.”
The Annual Review of Physiology: Past and Present
Authors: Hall Victor E. , Sonnenschein Ralph R.
Published: July 2003

When Isidore Edelman invited us to write an introductory chapter for this volume of the Annual Review of Physiology, we were delighted with the opportunity to give some of our thoughts and reminiscences about the Review. Our combined span of service as editors covered about 40 years, nearly the entire lifetime of the Review. Each of us had his own experiences and point of view, so rather than attempt a single presentation we have written the following separate sections.
Dual Protease Inhibitor Therapy in HIV-Infected Patients: Pharmacologic Rationale and Clinical Benefits
Authors: Flexner Charles
Published: July 2003

HIV protease inhibitors, as components of combination antiretroviral drug regimens, have substantially reduced the morbidity and mortality associated with HIV infection. They selectively block the action of the virus-encoded protease and stop the virus from replicating. In general, these drugs have poor systemic bioavailability and must be dosed with respect to meals for optimal absorption. Protease inhibitor–containing regimens require ingestion of a large number of capsules, are costly, and produce or are susceptible to metabolic drug interactions. Simultaneous administration of two protease inhibitors takes advantage of beneficial pharmacokinetic interactions and may circumvent many of the drugs’ undesirable pharmacologic properties. For example, ritonavir increases saquinavir concentrations at steady state by up to 30-fold, allowing reduction of saquinavir dose and dosing frequency. Ritonavir decreases the systemic clearance of indinavir and overcomes the deleterious effect of food on indinavir bioavailability. These benefits reflect inhibition of presystemic clearance and first-pass metabolism, as well as inhibition of systemic clearance mediated by hepatic cytochrome P450 3A4. Several dual protease inhibitor combination regimens have shown great promise in clinical trials and are now recommended as components of salvage therapy for HIV-infected patients.
THESUPREMECOURT INAMERICANPOLITICS
Authors: Baum Lawrence
Published: July 2003

▪ Abstract  The Supreme Court's role in American politics is a product of its interventions in public policy making and the impact of those interventions on government and society. The Court's frequent and substantial interventions during the past half century are especially striking, and their extent and their beneficiaries cannot be explained fully by major theories of the Court's behavior. The Court's rulings often receive negative responses from other policy makers, but even more noteworthy is the degree to which judges and administrators carry out the Court's policies and legislators leave those policies standing and the Court unscathed. Scholars who emphasize the Court's limited ability to change society make a strong case, but it is not clear to what extent the Court's limitations are unique to the judiciary and to what extent they reflect the limited powers of government in general.
GOVERNMENT TERMINATION
Authors: Laver Michael
Published: July 2003

▪ Abstract  This paper reviews a range of approaches to the analysis of government termination, by any account a very important substantive concern for political science. One essential preliminary matter is the distinction between government duration and government durability—the former an essentially empirical concept, the latter essentially theoretical. It is also important to note that empirical research into government termination is heavily conditioned by the precise definition of what marks the end of one government and the beginning of the next. Approaches to analyzing government termination can be divided into those that are fundamentally empirical and those based on a priori modeling. Both research traditions are reviewed. The empiricist approach has evolved into a body of work that applies increasingly sophisticated event-history models to a dataset that has become to a large extent common within the profession. The a priori approach has developed within the traditions of noncooperative game theory to model the responses of key actors to new information, for example, about the likely results of an election that might be called if the government were to fall. There is clearly unfulfilled potential to merge these two research traditions into a single more comprehensive account of government termination.
CURRENTCONTROVERSIES INFEMINISTTHEORY
Authors: Dietz Mary G.
Published: July 2003

▪ Abstract  Over the past two decades, academic feminism has differentiated and fragmented substantially in light of a wide range of new approaches in theory. This overview and assessment of the wide, diverse, and changing field of feminist theory gives particular attention to contestations surrounding the political theorizing of gender, identity, and subjectivity. Three divergent and oppositional perspectives—difference feminism, diversity feminism, and deconstruction feminism—frame current discussions regarding the “construction” of the female subject; the nature of sexual difference; the relation between sex and gender; the intersection of gender, race, class, sexuality, etc.; and the significance of “women” as a political category in feminism. The problem of epistemic identification (locating or dislocating the female subject, analyzing gender difference, politicizing identity) is also a central element in the theorizing of feminist politics, multicultural citizenship, justice, power, and the democratic public sphere. Within this domain, we find equally intense debates among feminist theorists concerning the meaning of feminist citizenship and the politics of recognition, as well as the relations between gender equality and cultural rights, feminism and multiculturalism, democracy and difference. Although the field is far from convergence even on the meaning of feminism itself, we might take its current state as a sign of its vitality and significance within the discourses of contemporary social and political theory.
DEMOCRATIC INDIVIDUALISM AND ITS CRITICS
Authors: Kateb George
Published: July 2003

▪ Abstract  Where democracy exists, there will be individualism. The historical record shows that democracy inevitably engenders individualism. This proposition will be challenged by those who think either that individualism can obtain in nondemocratic cultures or that democracy can exist without engendering individualism. The paper rejects both contentions. The defining characteristic of democracy is freedom, and the oldest democratic concept of freedom is the Greek one: To be free is to live as one likes. Versions of that definition are found wherever people are or aspire to be democratic. To live as one likes means that one is allowed to try out various roles in life. Each person is more than any single role, function, or place in society. Individualism consists in that idea. Only democracy inspires it. It is also true that democracy, in reaction, produces antidemocratic individualism. The greatest students of democratic individualism are Plato and Tocqueville, and they are also its profoundest critics. But contemporary critics are certainly worth scholarly attention.
WHATISTHIRDWORLDSECURITY?
Authors: Thomas Raju G.C.
Published: July 2003

▪ Abstract  This paper examines three images of the Third World (postcolonial, nonaligned, and less developed states) and four types of security (international, transnational, regional, and internal) on three continents (Asia, Africa, and Latin America). In the first image, the Third World is defined by a postcolonial racial divide between the former European colonial powers and their decolonized empires. The second image of the Third World is the lingering legacy of the Non-Aligned Movement, which comprised the states outside of the American and Soviet blocs. The third image is that of the less developed world and the continuing struggle between rich and poor, both among and within states. The four forms of security—international, transnational, regional, and internal—encompass interstate conflicts; civil wars, revolutions, and their spillover effects; nationalism and interethnic conflict and the prospect of failed states; the spread of nuclear, biological, and chemical weapons; transnational terrorism; the illicit narcotics trade; and perceived negative consequences of globalization.
Absorption and Translocation of Plant Regulators
Authors: van Overbeek J.
Published: July 2003

Naturally-occurring auxins, of which indoleacetic acid is the best known example, have a striking apex-to-base polar transport. This may have led to the belief that all plant regulators have a rather specific mode of absorption and of transport. However, since plant regulators now (5) include a wide variety of organic compounds this seems most unlikely.

Many of the phenomena which are involved in the absorption and translocation of regulators in plants are well known. However, a unified picture seems lacking. It is a rather new field, which one will not find discussed in standard texts of plant physiology. The significance of this subject is more than academic. In recent years sprays have been applied to plants for a multitude of practical purposes (106a).

New techniques have helped in the understanding of the principles of absorption and translocation. Enzymatic digestion is used for the isolation of the plant cuticle, a principal barrier through which materials must pass. Electron microscopy is showing its detailed structure. Radioactive tracers and chromatography have been useful in the microanalysis of materials, revealing their distribution on and in the plant. The author has attempted to outline the broad principles involved.
Heterologous Expression of Genes in Bacterial, Fungal, Animal, and Plant Cells
Authors: Frommer Wolf B. , Ninnemann Olaf
Published: July 2003

Analysis of gene function is of central importance for the understanding of physiological processes. Expression of genes in heterologous organisms has allowed the isolation of many important genes (e.g. for nutrient uptake and transport) and has contributed a lot to the functional analysis of the gene products. For animal research, expression in Xenopus oocytes and cell cultures are predominant techniques, whereas in the plant domain, yeast has become the prevalent expression system. This review provides a survey of this quickly developing field and intends to assist researchers in determining appropriate experimental approaches for specific biological questions. Because heterologous expression technology is of special value for the analysis of proteins that are difficult to handle biochemically, the examples given concentrate on membrane proteins, i.e. transporter proteins. Also included is a detailed discussion of the functional expression methodology and its use in identifying and characterizing genes and proteins.
Light-Regulated Transcription
Authors: Terzaghi William B. , Cashmore Anthony R.
Published: July 2003

This review focuses on light regulation of transcription, from light perception to changes in transcription, with an emphasis on regulatory elements in the promoters of light-regulated genes and proteins that bind to them. The abundance of over 100 mRNAs is regulated by light, and at least three photoreceptors influence transcription, but the importance of each photoreceptor may vary from gene to gene. Light-regulated promoters are composed of ubiquitous regulatory elements; the specific combination of elements appears to make a promoter light-regulated, and these combinations vary widely. Numerous proteins that bind to elements in light-regulated promoters have been identified and many have been cloned, but no cloned gene has been unequivocally assigned a function in light-regulated transcription. Substantial progress has been made in identifying steps in signal transduction from light perception to transcription, but these steps have yet to be assembled into complete pathways.
Biochemistry and Molecular Biology of the Isoprenoid Biosynthetic Pathway in Plants
Authors: Chappell Joseph
Published: July 2003

This review first summarizes the diverse nature of isoprenoids found in plants, emphasizing the wide range of physiological functions these compounds serve. The biosynthetic origins of isoprenoids have occupied chemists and biochemists for decades, and the second section of this review recaps some of the conceptual models used to rationalize key biosynthetic reactions in the isoprenoid pathway. The third section describes briefly some of the recently developed experimental systems that have helped researchers uncover much of the biochemistry and molecular biology of isoprenoids. The fourth section compares the deduced amino acid sequences of enzymes with similar catalytic functions and attempts to correlate these sequences with the known enzymology. The fifth and final section focuses on our limited understanding of how isoprenoid biosynthesis is regulated in plants.
Training in Work Organizations
Authors: Goldstein Irwin L.
Published: July 2003

This review examines issues and topics concerning systematic modes of instruction designed to produce environments that shape behavior to satisfy stated objectives. Training here is defined as the acquisition of skills, concepts, or attitudes that results in improved performance in an on-the-job environment. Even a cursory inspection of this review displays the diverse nature of literature in this field which includes such topics as: need assessment techniques, evaluation methodology, and particular modes of instruction; in addition, there are topics with social and political implications such as training for second careers and training hard-core unemployed youth. This is the first examination of the topic in this series since J. P. Campbell's (1971) review. Computer searches covering the period since his review produced over 3000 references from the Educational Resources Information Center and Psychological Abstracts bibliographic data bases. The resulting eye strain was partially alleviated by a set of informal decision rules which helped determine the materials read and considered for this review. First, consistent with the definition of training, the selection process emphasized topics related to systematic instruction designed to produce transfer in work organizations. Thus, topics that emphasized the development of basic principles in learning (e.g. massed vs spaced learning) were excluded unless the research was directly relevant to an instructional program for training purposes. Also, topics such as organization development which have implications for quality of work life and institutional effectiveness that extend beyond the considerations of most training programs were excluded as a separate topic. However, there is an attempt to describe relevant literature from a wide variety of disciplines which touch on many important developments. Therefore, this review examines discussions on such topics as criterion development, found in the educational psychology literature; need assessment methodology, developed in vocational education; and instructional systems approaches, evaluated in military environments.

This review also attempts to conceptualize training issues broadly. It would have been possible to complete this article by examining only the different types of training approaches utilized. However, such an approach would have excluded many important issues that should affect our understanding of training as a system within a work organization. For example, it is possible to consider training as part of the socialization process. Also, it is important to consider training and its evaluation as an intervention which affects the lives of people in work organizations. This review attempts to provide such a perspective as well as examine the more traditional topics.
Infant Mortality in Socially Vulnerable Populations
Authors: Nersesian William S.
Published: July 2003

Studies have shown for decades that certain subpopulations of infants, for example, those in poverty and in certain minority groups, are at substantially higher risk for illness and death than the national average. If mothers and infants of these “vulnerable populations” were as healthy as their “nonvulnerable” counterparts, as many as one third (approximately 12,000 deaths) of all infant deaths in the United States might be avoided each year. This paper is intended to document which infants are vulnerable, to quantitate the degree of risk where possible, and to outline potential changes in public policy that may lead to improvements in the health of these infants.
Statistical Issues in the Design of HIV Vaccine Trials
Authors: Schaper Carl , Fleming Thomas R. , Self Steven G. , Rida Wasima N.
Published: July 2003

HIV vaccine trials present significant challenges related to trial endpoints, vaccine efficacy measurement, and the role of nonvaccine interventions. Infection is a valid endpoint for detecting sterilizing immunity. But if the vaccine prevents AIDS without preventing infection, infection may be a misleading surrogate. Appropriate endpoints must be defined for other mechanisms of vaccine action. Direct, indirect, behavioral, and biological effects all determine vaccine efficacy. False security among HIV-vaccine recipients may make negative behavioral effects an important component of vaccine performance. Both biological potency and a more comprehensive program effectiveness should be measured. These goals may require unblinded designs or community randomization. Nonvaccine interventions are currently the only HIV-prevention strategy. Support for larger scale implementation requires more rigorous evaluation that is less dependent on self-reported behavioral changes. The vaccine trial cohorts provide a unique opportunity to cost-effectively evaluate behavioral interventions.