bluuebunny/crossref_metadata_2025 huggingface dataset:
CARBON SINKS IN TEMPERATE FORESTS
Authors: Martin Philippe H. , Nabuurs Gert-Jan , Aubinet Marc , Karjalainen Timo , Vine Edward L. , Kinsman John , Heath Linda S.
Published: July 2002

▪ Abstract  In addition to being scientifically exciting, commercially important, and environmentally essential, temperate forests have also become a key diplomatic item in international climate negotiations as potential sinks for carbon. This review presents the methods used to estimate carbon sequestration, identifies the constraints and opportunities for carbon sequestration in temperate forests, addresses the issues raised by the monitoring of carbon sequestration, and analyzes uncertainties pertaining to the sequestration of carbon by temperate forests. This review serves a dual purpose: It aims at informing policy makers about carbon sequestration in temperate forests and at making forest ecologists, biogeochemists, and atmospheric scientists aware of the structure of an international agreement to reduce CO2 and other greenhouse gas emissions and some of the real, still answered scientific questions that it poses.
WILD HOSTS OF PENTATOMIDS:Ecological Significance and Role in Their Pest Status on Crops
Authors: Panizzi Antônio R.
Published: July 2002

▪ Abstract  Phytophagous stink bugs (Heteroptera: Pentatomidae) are important pests of many crops, feeding mostly on seeds and immature fruits. During feeding they introduce their stylets to remove the cells' contents. The resulting damage includes drop and/or malformation of seeds and fruits. As stink bugs are generally polyphagous, they feed on cultivated and uncultivated plants; consequently, wild host plants play an important role in the increase in population levels of agricultural pest species. These plants are important food resources for development of nymphs and reproduction of adults. Because these bugs are multivoltine and feed in general on temporarily restricted food plants, host-switching from food plants of nymphs to those of adults is common and has varying effects on adult performance depending on the quality of the foods involved. Although polyphagous, local populations of many pentatomid species may show specific feeding habits, restricting their host range to fewer plant species. The knowledge of host plant sequences, including cultivated and uncultivated hosts, and the use of wild hosts as trap plants will improve management of pest species. Finally, future research should focus on determining which plants are preferably used by stink bugs, how they affect insect performance, at what rate populations increase on these plants, and how effective natural enemies are at this time.
EVOLUTION OFEXCLUSIVEPATERNALCARE INARTHROPODS
Authors: Tallamy Douglas W.
Published: July 2002

▪ Abstract  Exclusive male care of offspring is the rarest form of postzygotic parental care among animals and has arisen independently in only 13 arthropod taxa. To distinguish the effects of sexual selection from those of natural selection on the evolution of arthropod paternal care, predictions concerning several life-history and behavioral traits resulting from both forms of selection are made and tested across all known taxa with exclusive paternal care. Comparisons suggest parallels between prezygotic nuptial gifts and exclusive postzygotic male care and support the hypothesis that, in arthropods, male behaviors that enhance female reproductive success either directly, by releasing females from the fecundity constraints of maternal care (enhanced fecundity hypothesis), or indirectly, by identifying mates with superior genes (handicap principle), are traits on which sexual selection has acted. Under such conditions, males that are willing to guard young become preferred mates for gravid females and enjoy greater promiscuity than males that are unable or unwilling to guard. Females use nest construction or the act of guarding another female's eggs as honest signals of paternal intent and quality.
The Dynamics of Lava Flows
Authors: Griffiths R. W.
Published: July 2002

Lava flows are gravity currents of partially molten rock that cool as they flow, in some cases melting the surface over which they flow but in all cases gradually solidifying until they come to rest. They present a wide range of flow regimes from turbulent channel flows at moderate Reynolds numbers to extremely viscous or plastic, creeping flows, and even brittle rheology may play a role once some solid has formed. The cooling is governed by the coupling of heat transport in the flowing lava with transfer from the lava surface into the surrounding atmosphere or water or into the underlying solid, and it leads to large changes in rheology. Instabilities, mostly resulting from cooling, lead to flow branching, surface folding, rifting, and fracturing, and they contribute to the distinctive styles and surface appearances of different classes of flows. Theoretical and laboratory models have complemented field studies in developing the current understanding of lava flows, motivated by the extensive roles they play in the development of planetary crusts and ore deposits and by the immediate hazards posed to people and property. However, much remains to be learned about the mechanics governing creeping, turbulent, and transitional flows in the presence of large rheology change on cooling and particularly about the advance of flow fronts, flow instabilities, and the development of flow morphology. I introduce the dynamical problems involved in the study of lava flows and review modeling approaches.
RECOMBINATION AND RECOMBINATION-DEPENDENT DNA REPLICATION IN BACTERIOPHAGE T4
Authors: Mosig Gisela
Published: July 2002

▪ Abstract  General recombination is essential for growth of phage T4, because origin initiation of DNA replication is inactivated during development, and recombination-dependent initiation is necessary for continuing DNA replication. The requirement of recombination for T4 growth has apparently been a driving force to acquire and maintain multiple recombination mechanisms. This requirement makes this phage an excellent model to analyze several recombination mechanisms that appear redundant under optimal growth conditions but become essential under other conditions, or at different stages of the developmental program. The most important substrate for wild-type T4 recombination is single-stranded DNA generated by incomplete replication of natural or artificial chromosomal ends, or by nucleolytic degradation from induced breaks, or nicks. Recombination circumvents the further erosion of such ends. There are multiple proteins and multiple pathways to initiate formation of recombinants (by single-strand annealing or by strand invasion) and to convert recombinational intermediates into final recombinants (“cut and paste” or “cut and package”), or to initiate extensive DNA replication by “join-copy” or “join-cut-copy” mechanisms. Most T4 recombination is asymmetrical, favoring the initiation of replication. In wild-type T4 these pathways are integrated with physiological changes of other DNA transactions: mainly replication, transcription, and packaging. DNA replication and packaging enzymes participate in recombination, and recombination intermediates supply substrates for replication and packaging. The replicative recombination pathways are also important for transmission of intron DNA to intronless genomes (“homing”), and are implicated in horizontal transfer of foreign genes during evolution of the T-even phages. When horizontal transfer involves heteroduplex formation and repair, it is intrinsically mutagenic and contributes to generation of species barriers between phages.
Family Values in The Age of Genomics: Comparative Analyses of Temperate Bacteriophage HK022
Authors: Weisberg Robert A. , Gottesman Max E. , Hendrix Roger W. , Little John W.
Published: July 2002

▪ Abstract  HK022 is a temperate coliphage related to phage λ. Its chromosome has been completely sequenced, and several aspects of its life cycle have been intensively studied. In the overall arrangement, expression, and function of most of its genes, HK022 broadly resembles λ and other members of the λ family. Upon closer view, significant differences emerge. The differences reveal alternative strategies used by related phages to cope with similar problems and illuminate previously unknown regulatory and structural motifs. HK022 prophages protect lysogens from superinfection by producing a sequence-specific RNA binding protein that prematurely terminates nascent transcripts of infecting phage. It uses a novel RNA-based mechanism to antiterminate its own early transcription. The HK022 protein shell is strengthened by a complex pattern of covalent subunit interlinking to form a unitary structure that resembles chainmail armor. Its integrase and repressor proteins are similar to those of λ, but the differences provide insights into the evolution of biological specificity and the elements needed for construction of a stable genetic switch.
Building a Multicellular Organism
Authors: Kaiser Dale
Published: July 2002

▪ Abstract  Multicellular organisms appear to have arisen from unicells numerous times. Multicellular cyanobacteria arose early in the history of life on Earth. Multicellular forms have since arisen independently in each of the kingdoms and several times in some phyla. If the step from unicellular to multicellular life was taken early and frequently, the selective advantage of multicellularity may be large. By comparing the properties of a multicellular organism with those of its putative unicellular ancestor, it may be possible to identify the selective force(s). The independent instances of multicellularity reviewed indicate that advantages in feeding and in dispersion are common. The capacity for signaling between cells accompanies the evolution of multicellularity with cell differentiation.
Biology of Mammalian L1 Retrotransposons
Authors: Ostertag Eric M. , Kazazian Jr Haig H.
Published: July 2002

▪ Abstract  L1 retrotransposons comprise 17% of the human genome. Although most L1s are inactive, some elements remain capable of retrotransposition. L1 elements have a long evolutionary history dating to the beginnings of eukaryotic existence. Although many aspects of their retrotransposition mechanism remain poorly understood, they likely integrate into genomic DNA by a process called target primed reverse transcription. L1s have shaped mammalian genomes through a number of mechanisms. First, they have greatly expanded the genome both by their own retrotransposition and by providing the machinery necessary for the retrotransposition of other mobile elements, such as Alus. Second, they have shuffled non-L1 sequence throughout the genome by a process termed transduction. Third, they have affected gene expression by a number of mechanisms. For instance, they occasionally insert into genes and cause disease both in humans and in mice. L1 elements have proven useful as phylogenetic markers and may find other practical applications in gene discovery following insertional mutagenesis in mice and in the delivery of therapeutic genes.
Public Concern About Genetics
Authors: Reilly Philip R.
Published: July 2002

Throughout the twentieth century and continuing into the present, the general public has been fascinated by advances in genetic knowledge. At times, individuals and groups have either inadvertently or deliberately misused genetic knowledge in the service of political goals. At other times, advances in genetics have challenged deeply held societal or religious beliefs. During the 1990s, there were many advances that focused an unprecedented level of public attention and concern on genetics. In particular, the public has expressed deep concern about gene mapping, cloning, and genetically modified foods. In each case, the origin of the concern and the nature of the public response have been different. I consider these topics and argue that the scientific community must increase its commitment to public discourse.
THE STRUCTURE OF THE T CELL ANTIGEN RECEPTOR
Authors: Bentley Graham A. , Mariuzza Roy A.
Published: July 2002

▪ Abstract  Recent crystallographic studies of T cell antigen receptor (TCR) fragments from the α and β chains have now confirmed the expected structural similarity to corresponding immunoglobulin domains. Although the three-dimensional structure of a complete TCR αβ heterodimer has not yet been determined, these results support the view that the extracellular region should resemble an immunoglobulin Fab fragment with the antigen-binding site formed from peptide loops homologous to immunoglobulin complementarity-determining regions (CDR). These preliminary results suggest that CDR1 and CDR2 may be less variable in structure than their immunoglobulin counterparts, consistent with the idea that they may interact preferentially with the less polymorphic regions of the molecules of the major histocompatibility complex. The region on the variable β domain responsible for superantigen recognition is analyzed in detail. The implications for T cell activation from the interactions observed between domains of the α and β chains are also discussed in terms of possible dimerization and allosteric mechanisms.
CD22, A B LYMPHOCYTE–SPECIFIC ADHESION MOLECULE THAT REGULATES ANTIGEN RECEPTOR SIGNALING*
Authors: Tedder Thomas F. , Tuscano Joseph , Sato Shinichi , Kehrl John H.
Published: July 2002

▪ Abstract  The development of B lymphocytes is a highly regulated process that depends in part on lineage-specific cell surface molecules. In addition, transmembrane signals generated through the B cell antigen receptor and other surface molecules regulate B cell responses to foreign antigens. Recent studies reveal CD22 to be a functionally significant receptor during these processes. CD22 is first expressed in the cytoplasm of pro-B and pre-B cells, and on the surface as B cells mature to become IgD+. CD22 is a member of the Ig superfamily that serves as an adhesion receptor for sialic acid-bearing ligands expressed on erythrocytes and all leukocyte classes. In addition to its potential role as a mediator of intercellular interactions, signal transduction through CD22 can activate B cells and modulate antigen receptor signaling in vitro. CD22 signaling is mediated via interactions with a number of kinases and phosphatases that bind the cytoplasmic domain through phosphorylated tyrosine residues located within consensus TAM and TIM motifs. The phenotype of CD22-deficient mice suggests that CD22 is primarily involved in the generation of mature B cells within the bone marrow, blood, and marginal zones of lymphoid tissues. Most notable in CD22-deficient mice is a significant diminution of surface Ig levels in these B cell subpopulations, which suggests that CD22 functions in vivo to adjust the signaling threshold of cell surface antigen receptors. A further understanding of CD22 function is required and may reveal roles for CD22 in disease susceptibility or the development of autoimmunity.
ROLE OF COMPLEMENT IN HIV INFECTION
Authors: Stoiber Heribert , Clivio Alberto , Dierich Manfred P.
Published: July 2002

▪ Abstract  In human plasma, HIV activates the complement system, even in the absence of specific antibodies. Complement activation would, however, be harmful to the virus if the reactions were allowed to go to completion, since their final outcome would be virolysis. This is avoided by complement regulatory molecules, which either are included in the virus membrane upon budding from the infected cells (e.g. DAF/CD55) or are secondarily attached to HIV envelope glycoproteins as in the case of factor H. By using this strategy of interaction with complement components, HIV takes advantage of human complement activation for enhancement of infectivity, for follicular localization, and for broadening its target cell range at the same time that it displays an intrinsic resistance against the lytic action of human complement. This intrinsic resistance to complement-mediated virolysis can be overcome by monoclonal antibodies inhibiting recruitment of human factor H to the virus surface, suggesting a new therapeutic principle.
Noncytolytic Control of Viral Infections by the Innate and Adaptive ImmuneResponse
Authors: Guidotti Luca G. , Chisari Francis V.
Published: July 2002

This review describes the contribution of noncytolytic mechanisms to the control of viral infections with a particular emphasis on the role of cytokines in these processes. It has long been known that most cell types in the body respond to an incoming viral infection by rapidly secreting antiviral cytokines such as interferon alpha/beta (IFN-α/β). After binding to specific receptors on the surface of infected cells, IFN-α/β has the potential to trigger the activation of multiple noncytolytic intracellular antiviral pathways that can target many steps in the viral life cycle, thereby limiting the amplification and spread of the virus and attenuating the infection. Clearance of established viral infections, however, requires additional functions of the immune response. The accepted dogma is that complete clearance of intracellular viruses by the immune response depends on the destruction of infected cells by the effector cells of the innate and adaptive immune system [natural killer (NK) cells and cytotoxic T cells (CTLs)]. This notion, however, has been recently challenged by experimental evidence showing that much of the antiviral potential of these cells reflects their ability to produce antiviral cytokines such as IFN-γ and tumor necrosis factor (TNF)-α at the site of the infection. Indeed, these cytokines can purge viruses from infected cells noncytopathically as long as the cell is able to activate antiviral mechanisms and the virus is sensitive to them. Importantly, the same cytokines also control viral infections indirectly, by modulating the induction, amplification, recruitment, and effector functions of the immune response and by upregulating antigen processing and display of viral epitopes at the surface of infected cells. In keeping with these concepts, it is not surprising that a number of viruses encode proteins that have the potential to inhibit the antiviral activity of cytokines.
RECENT DEVELOPMENTS IN CONDUCTOR PROCESSING OF HIGH IRREVERSIBILITY FIELD SUPERCONDUCTORS
Authors: MacManus-Driscoll J. L.
Published: July 2002

▪ Abstract  This review discusses the current status and future of high irreversibility field superconductor processing for conductor applications. The topic is introduced by comparing the properties and processability of the most widely studied superconducting materials, and by highlighting the application goals requirements. A major section of the review is concerned with thin film routes for fabricating the high irreversibility superconductor, YBa2Cu3O7−x, because this is an area where there has been much recent success. The prospect of improved conductor properties through processing refinements, as well as the potential for scale-up and cost issues, is considered for the thin film routes.

Bearing in mind the industrial limitations of the thin film technologies, the possibility of adopting an “all thick film” or hybrid “thin film/thick film” technology is considered, with examples of success in this area being given. Various thick film deposition methods are explored, as well as the reaction steps required to achieve the necessary film texture for high-current-carrying conductors.
SPIN-TUNNELING IN FERROMAGNETIC JUNCTIONS
Authors: Moodera Jagadeesh S. , Nassar Joaquim , Mathon George
Published: July 2002

▪ Abstract  Based on the spin conservation in electron tunneling across an insulator (I) and the spin polarization of conduction electrons in ferromagnets (FM) established by Meservey and Tedrow, Jullière put forward a quantitative model (1975) showing that tunneling in FM-I-FM junctions should lead to a large junction magnetoresistance (JMR). This conjecture was realized with repeatable results only in 1995, and since then JMR values >30% have been achieved at room temperature. This phenomenon has tremendous potential for applications as nonvolatile magnetic memory elements, read heads, and picotesla field sensors.

We review the experimental results and the current theoretical understanding of FM-I-FM tunneling and its dependence on bias, temperature, and barrier characteristics. The influence of inelastic tunneling processes and material properties on the JMR is extensively discussed. Early theories are reviewed and their relationship to the linear response theory is presented. Future directions, both from the point of fundamental physics as well as applications, are also covered.
Block Copolymer Thin Films: Physics and Applications
Authors: Fasolka Michael J , Mayes Anne M
Published: July 2002

▪ Abstract  A two-part review of research concerning block copolymer thin films is presented. The first section summarizes experimental and theoretical studies of the fundamental physics of these systems, concentrating upon the forces that govern film morphology. The role of film thickness and surface energetics on the morphology of compositionally symmetric, amorphous diblock copolymer films is emphasized, including considerations of boundary condition symmetry, so-called hybrid structures, and surface chemical expression. Discussions of compositionally asymmetric systems and emerging research areas, e.g., liquid-crystalline and A-B-C triblock systems, are also included. In the second section, technological applications of block copolymer films, e.g., as lithographic masks and photonic materials, are considered. Particular attention is paid to means by which microphase domain order and orientation can be controlled, including exploitation of thickness and surface effects, the application of external fields, and the use of patterned substrates.
The Role of Oncogenes in Hematologic Malignancies
Authors: Boxer Linda M.
Published: July 2002

Oncogenes are activated forms of cellular genes involved in normal cell growth and development. Some oncogenes play a role in human malignancies. In hematologic malignancies, researchers have identified many transcription factors as oncogenes based on one of the following criteria: their association with transforming retroviruses in animals, their translocation into either the immunoglobulin or T-cell receptor loci, or the production of fusion proteins resulting from chromosomal translocations. The molecular characterization of oncogenes in hematologic malignancies has led to the discovery of new methods for diagnosis and detection of minimal residual disease. In the future, researchers probably will develop novel treatment strategies to interfere with the function of these oncogenes.
ORGAN PRESERVATION
Authors: Southard, M.D James H. , Belzer, M.D Folkert O.
Published: July 2002

▪ Abstract  Organ preservation is the supply line for organ transplantation. Currently, the liver, pancreas, and kidney can be successfully preserved for up to two days by flushing the organs with the University of Wisconsin (UW) organ preservation solution and storing them at hypothermia (0–5° C). The UW solution is effective because it uses a number of cell impermeant agents (lactobionic acid, raffinose, hydroxyethyl starch) that prevent the cells from swelling during cold ischemic storage. Additionally, the UW solution contains glutathione and adenosine, agents that may stimulate recovery of normal metabolism upon reperfusion by augmenting the antioxidant capacity of the organs (glutathione) or by stimulating high-energy phosphate generation (adenosine) upon reperfusion.

Although this method of organ preservation is effective, some organs (5–15% of livers and 20–30% of kidneys) do not function well upon transplant. Injury may be preservation related but may also result from donor and recipient factors that render the organs more susceptible to preservation damage. Results with continuous perfusion of kidneys in the clinics show a reduction in preservation/reperfusion damage. This may be a more appropriate preservation method than cold storage. In this chapter we discuss the development and use of the UW solution and present clinical results. Although intraabdominal organs are well preserved at present, intrathoracic organs (lungs and heart) are less well preserved, and better methods for preservation of these organs are needed for increased use of lung and heart transplantation.
ALCOHOL, CORONARY DISEASE, AND HYPERTENSION
Authors: Klatsky, M.D A. L.
Published: July 2002

▪ Abstract  Disparities in the relationships between alcohol consumption and various cardiovascular conditions are now evident, with complex interrelationships between conditions. An inverse relationship of alcohol use to coronary heart disease is supported by many population studies. Interpretation of these data as a protective effect of alcohol against coronary disease is strengthened by plausible mechanisms. Although some experimental data suggest the hypothesis that wine, in particular, has additional protective benefit, prospective studies show no consensus on this point. Strong, consistent epidemiologic data support a relationship of heavier drinking to hypertension. Intervention studies show a pressor effect of alcohol, which appears and regresses within several days, but a mechanism has not yet been established. As with most aspects of alcohol and health effects, the data do not suggest monotonic relationships of alcohol with these conditions. Thus, amount of alcohol taken is a crucial consideration. Advice to concerned persons needs to take into account individual factors in drinkers or potential drinkers.
Evaluation of the Patient with Recurrent Bacterial Infections
Authors: Holland Steven M. , Gallin John I.
Published: July 2002

Recurrent bacterial infection is a complaint encountered regularly in the course of both adult and pediatric care. Defects of neutrophils and monocytes are most commonly associated with recurrent infection, but abnormalities of immunoglobulins and complement must be considered. Defensins, small antibacterial peptides, have been implicated recently in some of the infectious diathesis of cystic fibrosis. A thorough history and physical examination focused on severity, sequelae, and microbiology of infections can usually determine whether a patient needs further evaluation. The diseases and syndromes most frequently associated with recurrent infection are presented, along with discriminating clinical, pathologic, and microbiologic features.
Progress with Chronic Myelogenous Leukemia: A Personal Perspective over Four Decades
Authors: Nowell Peter C.
Published: July 2002

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▪ Abstract  Our understanding and treatment of chronic myelogenous leukemia (CML) has progressed since 1960 in parallel with work on cancer in general. CML provided the first evidence of a specific genetic change associated with a human cancer (the Philadelphia chromosome) and the clonal nature of these disorders. With improved cytogenetic and molecular techniques over subsequent decades, the specific genetic rearrangements of CML and many other tumors were defined and the complex mechanisms of carcinogenesis gradually unraveled. During this period, improved treatments for CML (chemotherapy, interferon, bone marrow transplantation) were implemented, and therapy targeted to the specific genetic change in the leukemic cells has recently been brought to promising clinical trials. Similar efforts are under way for other human cancers, and although the problem is enormously complex, there is real hope for major improvements in controlling these disorders.
Immune Reconstitution in Patients with HIV Infection
Authors: Sempowski Gregory D. , Haynes Barton F.
Published: July 2002

▪ Abstract  The peripheral T cell pool is damaged by HIV-1 infection and can be regenerated by production of new T lymphocytes either from the thymus or from proliferation of post-thymic T cells. A critical question for AIDS patients is whether treatment with antiretroviral drugs can restore the capability to produce new T lymphocytes. The development of a new assay of thymus function in adults (the measurement of T cell receptor excision circles, TRECs), and studies of thymus biopsies in untreated and treated HIV-1-infected patients, have suggested that in select patients the thymus can regenerate on antiretroviral therapy. New strategies to overcome the thymic atrophy of aging are needed to improve thymic function in the majority of AIDS patients.
Pathogenicity Islands and the Evolution of Microbes
Authors: Hacker Jörg , Kaper James B.
Published: July 2002

▪ Abstract  Virulence factors of pathogenic bacteria (adhesins, toxins, invasins, protein secretion systems, iron uptake systems, and others) may be encoded by particular regions of the prokaryotic genome termed pathogenicity islands. Pathogenicity islands were first described in human pathogens of the species Escherichia coli, but have recently been found in the genomes of various pathogens of humans, animals, and plants. Pathogenicity islands comprise large genomic regions [10–200 kilobases (kb) in size] that are present on the genomes of pathogenic strains but absent from the genomes of nonpathogenic members of the same or related species. The finding that the G+C content of pathogenicity islands often differs from that of the rest of the genome, the presence of direct repeats at their ends, the association of pathogenicity islands with transfer RNA genes, the presence of integrase determinants and other mobility loci, and their genetic instability argue for the generation of pathogenicity islands by horizontal gene transfer, a process that is well known to contribute to microbial evolution. In this article we review these and other aspects of pathogenicity islands and discuss the concept that they represent a subclass of genomic islands. Genomic islands are present in the majority of genomes of pathogenic as well as nonpathogenic bacteria and may encode accessory functions which have been previously spread among bacterial populations.
Phages of Dairy Bacteria
Authors: Brüssow Harald
Published: July 2002

▪ Abstract  Bacteriophages of lactic acid bacteria are a threat to industrial milk fermentation. Owing to their economical importance, dairy phages became the most thoroughly sequenced phage group in the database. Comparative genomics identified related cos-site and pac-site phages, respectively, in lactococci, lactic streptococci and lactobacilli. Each group was represented with closely related temperate and virulent phages. Over the structural genes their gene maps resembled that of lambdoid coliphages, suggesting distant evolutionary relationships. Despite a lack of sequence similarity, a number of biochemical characteristics of these dairy phages are lambda-like (genetic switch, DNA packaging, head and tail morphogenesis, and integration, but not excision). These dairy phages thus provide interesting variations to the phage λ paradigm. The structural gene cluster of Lactococcus phage r1t resembled that of phages from mycobacteria. Virulent lactococcal phages with prolate heads (c2-like genus of Siphoviridae), in contrast, have no known counterparts in other bacterial genera.
MOLECULAR MECHANISMS OF VITAMIN E TRANSPORT
Authors: Traber Maret G. , Arai Hiroyuki
Published: July 2002

▪ Abstract  If the function of vitamin E is that of an antioxidant and the various forms of vitamin E have similar antioxidant activities, then why does RRR-α-tocopherol have the highest biologic activity? This chapter describes how interactions by investigators from various scientific disciplines using stable isotopes, molecular biology tools, and sophisticated genetic studies of humans with vitamin E deficiency have led to an understanding of this problem. This chapter provides an overview of (a) studies using deuterated tocopherols that demonstrated that the plasma preference for α-tocopherol is dependent on metabolic processes in the liver; (b) the isolation, molecular biology, and function of the α-tocopherol transfer protein; and (c) studies that demonstrated that patients who were vitamin E deficient as a result of no known cause had defective α-tocopherol transfer protein genes. Finally, we focus on the future—what remains to be learned about the regulation of vitamin E in tissues.
MEDICATION COMPLIANCE AS A FEATURE IN DRUG DEVELOPMENT
Authors: Kastrissios and H. , Blaschke T. F.
Published: July 2002

▪ Abstract  Well-designed clinical trials maximize the information that can be obtained regarding the clinical pharmacology of a drug and, in turn, can streamline and enhance the drug development process. Until recently, little emphasis has been placed on integrating the role of variability in individual patterns of drug-taking into the drug development process.

With the use of electronic monitoring, the temporal relationship between an individual's pattern of dosing and the prescribed regimen may be examined, and individual drug exposure may be estimated based on the actual history of dosing. As a result, accurate estimation of exposure-response relationships (or surrogate markers of response) can be obtained. Considerations in the design of clinical trials must therefore be expanded to include appropriate methods to measure compliance, sufficient frequency of monitoring to allow the time course of response to be mapped, and the use of statistically valid methods of data analysis.
CONTROLLED MOLECULAR ADSORPTION ON SILICON: Laying a Foundation for Molecular Devices
Authors: Wolkow Robert A.
Published: July 2002

▪ Abstract  This review is about understanding and controlling organic molecular adsorption on silicon. The goal is to provide a microscopic picture of structure and bonding in covalently attached molecule-silicon surface systems. The bias here is that an unprecedented, detailed understanding of adsorbate-surface structures is required in order to gain the control necessary to incorporate organic function into existing technologies or, eventually, to make new molecule-scale devices. A discussion of recent studies of adsorbate structure is presented. This includes simple alkenes, polyenes, benzene, and carene adsorbed on Si(100). Also included is a discussion of wet chemical procedures for forming alkyl and alkoxy covalently functionalized silicon. These discussions are presented together with comments on the related issues of adsorption dynamics and nano-scale manipulation in an effort to point the way toward principles and procedures that will allow the hybrid properties of organic molecules and surfaces to be harnessed.
MODULATION OF VASOPRESSIN-ELICITED WATER TRANSPORT BY TRAFFICKING OF AQUAPORIN2-CONTAINING VESICLES
Authors: Ward Donald T. , Hammond Timothy G. , Harris H. William
Published: July 2002

▪ Abstract  Vasopressin or AVP regulates water reabsorption by the kidney inner medullary collecting duct (IMCD) through the insertion and removal of aquaporin (AQP) 2 water channels into the IMCD apical membrane. AVP-elicited trafficking of AQP2 with the apical membrane occurs via a specialized population of vesicles that resemble synaptic vesicles in neurons. AQP2 vesicles and the IMCD apical membrane contain homologs of vesicle-targeting and signal transduction proteins found in neurons. Expression studies of AQP2, including human AQP2 mutants, suggest that the carboxyl-terminal domain of AQP2 is important in AQP2 trafficking, particularly as a site for cAMP-dependent protein kinase phosphorylation. These present data reveal that IMCD cells possess a complex integrated-signaling and vesicle-trafficking machinery that provides integration of AVP-elicited water transport with many other parameters within the IMCD cell as well as kidney.
Resurgence of Sodium Channel Research
Authors: Goldin Alan L
Published: July 2002

▪ Abstract  A variety of isoforms of mammalian voltage-gated sodium channels have been described. Ten genes encoding sodium channel α subunits have been identified, and nine of those isoforms have been functionally expressed in exogenous systems. The α subunit is associated with accessory β subunits in some tissues, and three genes encoding different β subunits have been identified. The α subunit isoforms have distinct patterns of development and localization in the nervous system, skeletal and cardiac muscle. In addition, many of the isoforms demonstrate subtle differences in their functional properties. However, there are no clear subfamilies of the channels, unlike the situation with potassium and calcium channels. The subtle differences in the functional properties of the sodium channel isoforms result in unique conductances in specific cell types, which have important physiological effects for the organism. Small alterations in the electrophysiological properties of the channel resulting from mutations in specific isoforms cause human diseases such as periodic paralysis, long QT syndrome, and epilepsy.
Molecular Aspects of Renal Anionic Drug Transport
Authors: Russel Frans G. M. , Masereeuw Rosalinde , van Aubel Rémon A. M. H.
Published: July 2002

▪ Abstract  Multiple organic anion transporters in the proximal tubule of the kidney are involved in the secretion of drugs, toxic compounds, and their metabolites. Many of these compounds are potentially hazardous on accumulation, and it is therefore not surprising that the proximal tubule is also an important target for toxicity. In the past few years, considerable progress has been made in the cloning of these transporters and their functional characterization following heterologous expression. Members of the organic anion transporter (OAT), organic anion transporting polypeptide (OATP), multidrug resistance protein (MRP), sodium-phosphate transporter (NPT), and peptide transporter (PEPT) families have been identified in the kidney. In this review, we summarize our current knowledge on their localization, molecular and functional characteristics, and substrate and inhibitor specificity. A major challenge for the future will be to understand how these transporters work in concert to accomplish the renal secretion of specific anionic substrates.
MISPERCEPTIONS ABOUT PERCEPTUAL BIAS
Authors: Gerber Alan , Green Donald
Published: July 2002

▪ Abstract  Do people assimilate new information in an efficient and unbiased manner—that is, do they update prior beliefs in accordance with Bayes' rule? Or are they selective in the way that they gather and absorb new information? Although many classic studies in political science and psychology contend that people resist discordant information, more recent research has tended to call the selective perception hypothesis into question. We synthesize the literatures on biased assimilation and belief polarization using a formal model that encompasses both Bayesian and biased learning. The analysis reveals (a) the conditions under which these phenomena may be consistent with Bayesian learning, (b) the methodological inadequacy of certain research designs that fail to control for preferences or prior information, and (c) the limited support that exists for the more extreme variants of the selective perception hypothesis.
PERFORMANCE EVALUATION IN WORK SETTINGS
Authors: Arvey R. D. , Murphy K. R.
Published: July 2002

▪ Abstract  Recent research from 1993 on performance evaluations in work settings is reviewed and integrated with the prior reset and historical bases. Contemporary research reflects several themes: General models of job performance are being developed, the job performance domain is being expanded, research continues to explore the psychometric characteristics of performance ratings, research is developing on potential bias in ratings, rater training is examined, and research continues in terms of efforts to attach utility values to rated performance. We conclude that research is progressing in traditional content areas as well in the exploration of new ground. Researchers are recognizing that job performance is more than just the execution of specific tasks and that it involves a wider array of important organizational activities. There is also an increased optimism regarding the use of supervisory ratings and recognition that such “subjective” appraisal instruments do not automatically translate into rater error or bias.
QUANTIFYING THE INFORMATION VALUE OF CLINICAL ASSESSMENTS WITH SIGNAL DETECTION THEORY
Authors: McFall Richard M. , Treat Teresa A.
Published: July 2002

▪ Abstract  The aim of clinical assessment is to gather data that allow us to reduce uncertainty regarding the probabilities of events. This is a Bayesian view of assessment that is consistent with the well-known concept of incremental validity. Conventional approaches to evaluating the accuracy of assessment methods are confounded by the choice of cutting points, by the base rates of the events, and by the assessment goal (e.g. nomothetic vs idiographic predictions). Clinical assessors need a common metric for quantifying the information value of assessment data, independent of the cutting points, base rates, or particular application. Signal detection theory (SDT) provides such a metric. We review SDT's history, concepts, and methods and provide examples of its application to a variety of assessment problems.
New Perspectives and Evidence on Political Communication and Campaign Effects
Authors: Iyengar Shanto , Simon Adam F.
Published: July 2002

We review recent empirical evidence that shows political campaigns are more potent than widely believed, focusing on the conceptual and methodological advances that have produced these findings. Conceptually, a broader definition of effects—that includes learning and agenda-control, as well as vote choice—characterizes contemporary research. This research also features two kinds of interactive models that are more complex than the traditional hypodermic (message-based) approach. The resonance model considers the relationship between message content and receivers’ predispositions, while the strategic model highlights the interactions between competing messages. Finally, we attribute the emergence of stronger evidence in favor of campaign effects to the use of new methodologies including experimentation and content analysis, as well as the more sophisticated use of sample surveys.
DECLINING VIOLENT CRIME RATES IN THE 1990S: Predicting Crime Booms and Busts
Authors: LaFree Gary
Published: July 2002

▪ Abstract  The United States in the 1990s has experienced the greatest sustained decline in violent crime rates since World War II—even though rates thus far have not fallen as rapidly as they increased during the crime boom of the 1960s and early 1970s. I review a set of exogenous and policy-related explanations for the earlier crime boom and for the crime bust of the 1990s. I argue that our understanding of crime trends is hampered by a lack of longitudinal analysis and by ahistorical approaches. I identify a set of questions, concepts, and research opportunities raised by taking a more comprehensive look at crime waves.
Dynamic Nature of Atrial Fibrillation Substrate During Development and Reversal of Heart Failure in Dogs
Authors: Shinagawa Kaori , Shi Yan-Fen , Tardif Jean-Claude , Leung Tack-Ki , Nattel Stanley
Published: July 2002

Background
—

Clinical atrial fibrillation (AF) often results from pathologies that cause atrial structural remodeling. The reversibility of arrhythmogenic structural remodeling on removal of the underlying stimulus has not been studied systematically.

Methods and Results
—

Chronically instrumented dogs were subjected to 4 to 6 weeks of ventricular tachypacing (VTP; 220 to 240 bpm) to induce congestive heart failure (CHF), followed by a 5-week recovery period leading to hemodynamic normalization at 5-week recovery (Wk5
rec
). The duration of burst pacing–induced AF under ketamine/diazepam/isoflurane anesthesia increased progressively during VTP and recovered toward baseline during the recovery period, paralleling changes in atrial dimensions. However, even at full recovery, sustained AF could still be induced under relatively vagotonic morphine/chloralose anesthesia. Wk5
rec
dogs showed no recovery of CHF-induced atrial fibrosis (3.1±0.3% for controls versus 10.7±1.0% for CHF and 12.0±0.8% for Wk5
rec
dogs) or local conduction abnormalities (conduction heterogeneity index 1.8±0.1 in controls versus 2.3±0.1 in CHF and 2.2±0.2 in Wk5
rec
dogs). One week of atrial tachypacing failed to affect the right atrial effective refractory period significantly in CHF dogs but caused highly significant effective refractory period reductions and atrial vulnerability increases in Wk5
rec
dogs.

Conclusions
—

Reversal of CHF is followed by normalized atrial function and decreased duration of AF; however, fibrosis and conduction abnormalities are not reversible, and a substrate that can support prolonged AF remains. Early intervention to prevent fixed structural abnormalities may be important in patients with conditions that predispose to the arrhythmia.
Antioxidant Improves Smooth Muscle Sarco/Endoplasmic Reticulum Ca
2+
-ATPase Function and Lowers Tyrosine Nitration in Hypercholesterolemia and Improves Nitric Oxide–Induced Relaxation
Authors: Adachi Takeshi , Matsui Reiko , Xu Shanqin , Kirber Michael , Lazar Harold L. , Sharov Victor S. , Schöneich Christian , Cohen Richard A.
Published: July 2002

Antioxidants improve endothelial function in hypercholesterolemia (HC); however, whether this includes improvement of the vascular smooth muscle response to NO is unknown. NO relaxes arteries, in part, by stimulating Ca
2+
uptake via sarco/endoplasmic reticulum Ca
2+
-ATPase (SERCA) in aortic smooth muscle, and HC impairs SERCA function and the response to NO. HC induces oxidative stress, which could impair SERCA function. To study the effect of antioxidants, which are known to improve endothelium-dependent relaxation in HC, smooth muscle SERCA activity and NO-induced relaxation were studied in rabbits fed normal chow or a 0.5% cholesterol diet for 13 weeks. The antioxidant

t

-butylhydroxytoluene (BHT, 1%) was mixed with the HC diet in the last 3 weeks. HC impaired acetylcholine- and NO-induced relaxation, and these were restored by BHT. After inhibiting SERCA with thapsigargin, no difference existed in NO-induced relaxation among the three groups. Reduced aortic SERCA activity in HC was restored by BHT without changing SERCA protein expression. 3-Nitrotyrosine was notably increased in the media of the HC aorta, where it colocalized with SERCA. Tyrosine-nitrated SERCA protein was immunoprecipitated in the aortas of HC rabbits, where it was decreased by BHT, and it was also detected in the aortas of atherosclerotic humans. Thus, the antioxidant reverses impaired smooth muscle SERCA function in HC, and this is correlated with the improved relaxation to NO. These beneficial effects may depend on reducing the direct effects on SERCA of reactive oxygen species that are augmented in HC.
New Considerations in Analyzing Stroke and Heart Disease Mortality Trends
Authors: Gillum R.F.
Published: July 2002

Background

—

Monitoring of trends and patterns of stroke mortality will be of utmost importance in the coming decade. Two innovations in vital statistics may complicate this task and must be brought to the attention of both researchers and readers of research reports: the new Year 2000 Age Standard and the
International Statistical Classification of Diseases and Related Health Problems, 10th Revision
(
ICD-10
).

Summary of Review

—

For cerebrovascular diseases, the age-adjusted death rate is 2.4 times higher with the use of the year 2000 standard than with the use of the old 1940 standard. However, if rates for all years are computed with the use of the same age standard, the percent change from 1979 to 1995 is similar according to the 1940 standard (−35.8%) or the year 2000 standard (−34.3%). Another important effect of the change to the year 2000 standard is to reduce black/white differentials in age-adjusted death rates. Major discontinuities are not observed for mortality trends in cerebrovascular disease or heart disease between
International Classification of Diseases, Ninth Revision
(
ICD-9
) (1979–1998) and
ICD-10
(1999 and following years) classifications.

Conclusions

—

All data users must exercise caution to specify the age standard used when assessing or presenting age-adjusted rates over time or between groups. The comparability of
ICD
codes chosen for years before 1999 versus 1999 or following years must be checked to distinguish changes due to coding from true changes in mortality levels.