bluuebunny/crossref_metadata_2025 huggingface dataset:
FLUID MECHANICS OF SPIN CASTING OF METALS
Authors: Steen Paul H. , Karcher Christian
Published: July 2002

▪ Abstract  Casting of molten metals against a spinning wheel substrate is considered. Issues of fluid mechanics divide between steady and unsteady behavior (stability). The previous work on steady casting is hung on a framework provided by the long-puddle model of planar flow casting. Heat and fluid flow interact only through the shape of the solidification front in this case. In contrast, there is little previous work concerning stability issues. Stability is discussed in a broad-brush manner using the planar flow process for illustration. Issues range from meniscus motion and resulting ribbon texture to morphological-type instabilities of the solidification front. Fundamental and applied questions arise for both steady and unsteady behavior.
LEWIS FRY RICHARDSON AND HIS CONTRIBUTIONS TO MATHEMATICS, METEOROLOGY, AND MODELS OF CONFLICT
Authors: Hunt J.C.R.
Published: July 2002

[Figure: see text]

▪ Abstract  The life and major scientific contributions of Lewis Fry Richardson (1881–1953) are reviewed, with particular emphasis on his pioneering work in numerical analysis, meteorology, and numerical weather prediction. His later work on mathematical modeling of psychology, causes of conflict, and the statistics of wars is outlined in terms understandable to fluid dynamicists. It is included because it led to Richardson's discovery of one aspect of fractals, an analytical technique now recognized as valuable in the study of complex fluid motions.
TRANSPORT BY COHERENT BAROTROPIC VORTICES
Authors: Provenzale Antonello
Published: July 2002

▪ Abstract  This article reviews the transport properties of coherent vortices in rotating barotropic flows. It is shown that vortices induce regular Lagrangian motion inside their cores and are highly impermeable to inward and outward particle fluxes. Passive tracers can be trapped inside vortex cores for long times and are transported by the vortex motion over large distances. Absolute dispersion in vortex-dominated flows is discussed by studying particle dynamics in 2D turbulence, point-vortex systems, and subsurface float trajectories in the ocean. Finally, it is shown that anticyclonic coherent vortices in cyclonically rotating reference frames can concentrate heavy impurities (e.g. dust grains) in their cores. This process may play an important role in the formation of planetesimals in the early solar nebula.
BACTERIAL DIVERSITY BASED ON TYPE II DNA TOPOISOMERASE GENES
Authors: Mun Huang Wai
Published: July 2002

▪ Abstract  Type II DNA topoisomerases are essential and ubiquitous DNA metabolic enzymes that alter DNA topology. Eubacteria have two indispensable type II DNA topoisomerases, DNA gyrase encoded by gyrB and gyrA and topoisomerase IV encoded by parE and parC. These genes belong to a single family whose members span both eukaryotes and prokaryotes. The highly conserved motifs in these genes provide a rationale for the design of universal primers used in the polymerase chain reaction in order to systematically generate a data set suitable for bacterial diversity studies at the macro-diversity level, as well as at the micro-diversity level displaying individual species and isolates. This family of genes is the subject of intensive biochemical and genetic analyses, which provide an opportunity for comprehensive understanding of sequence conservation and variability and their relationship to function. These genes are ideally suited for microbial identification and biodiversity analyses.
LIGAND RECOGNITION BY αβ T CELL RECEPTORS
Authors: Davis Mark M. , Boniface J. Jay , Reich Ziv , Lyons Daniel , Hampl Johannes , Arden Bernhard , Chien Yueh-hsiu
Published: July 2002

▪ Abstract  While still incomplete, the first data concerning the biochemistry of T cell receptor–ligand interactions in cell-free systems seem to have considerable predictive value regarding whether a T cell response is strong or weak or suppressive. This data will help considerably in elucidating the mechanisms behind T cell responsiveness. Also of great interest are the first structures of T cell receptor molecules and, particularly, TCR-ligand complexes. These appear to confirm earlier suggestions of a fixed orientation for TCR engagement with peptide/MHC and should form the basis for understanding higher oligomers, evidence for which has also just emerged. We conclude with an analysis of the highly diverse CDR3 loops found in all antigen receptor molecules and suggest that such regions form the core of both TCR and antibody specificity.
STRUCTURAL BASIS OF T CELL RECOGNITION
Authors: Garcia K. Christopher , Teyton Luc , Wilson Ian A.
Published: July 2002

▪ Abstract  Exciting breakthroughs in the last two years have begun to elucidate the structural basis of cellular immune recognition. Crystal structures have been determined for full-length and truncated forms of αβ T cell receptor (TCR) heterodimers, both alone and in complex with their peptide-MHC (pMHC) ligands or with anti-TCR antibodies. In addition, a truncated CD8 coreceptor has been visualized with a pMHC. Aided in large part by the substantial body of knowledge accumulated over the last 25 years on antibody structure, a number of general conclusions about TCR structure and its recognition of antigen can already be derived from the relatively few TCR structures that have been determined. Small, but important, variations between TCR and antibody structures bear on their functional differences as well as on their specific antigen recognition requirements. As observed in antibodies, canonical CDR loop structures are already emerging for some of the TCR CDR loops. Highly similar docking orientations of the TCR Vα domains in the TCR/pMHC complex appear to play a primary role in dictating orientation, but the Vβ positions diverge widely. Similar TCR contact positions, but whose exact amino acid content can vary, coupled with relatively poor interface shape complementarity, may explain the flexibility and short half-lives of many TCR interactions with pMHC. Here we summarize the current state of this field, and suggest that the knowledge gap between the three-dimensional structure and the signaling function of the TCR can be bridged through a synthesis of molecular biological and biophysical techniques.
INTEGRATION OF T CELL RECEPTOR–DEPENDENT SIGNALING PATHWAYS BY ADAPTER PROTEINS
Authors: Clements James L. , Boerth Nancy J. , Lee Jong Ran , Koretzky Gary A.
Published: July 2002

▪ Abstract  The initiation of biochemical signal transduction following ligation of surface receptors with intrinsic cytoplasmic tyrosine kinase activity is common for many cell types. T lymphocytes also require activation of tyrosine kinases following T cell receptor (TCR) ligation for maximal stimulation. However, the TCR has no intrinsic tyrosine kinase activity. Instead, the TCR must rely on cytoplasmic tyrosine kinases that localize to the TCR complex and initiate TCR-mediated signaling events. Although much has been learned regarding how these cytosolic tyrosine kinases are activated and recruited to the TCR complex, relatively little is understood about how these initial events are translated into transcriptional activation of genes that regulate cytokine production, cell proliferation, and cell death. Recently, it has become clear that the class of intracellular molecules known collectively as adapter proteins, molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity, serve to couple proximal biochemical events initiated by TCR ligation with more distal signaling pathways.
Specificity and Degeneracy in Antigen Recognition: Yin and Yang in the Immune System
Authors: Eisen Herman N.
Published: July 2002

One of the hallmarks of the immune system is specificity, a concept based on innumerable observations that antibodies react with the substance that elicited their production and only a few other structurally similar substances. The study of T cells has begun to suggest, however, that in responses mediated by their antibody-like receptors (T cell receptor or TCR) an individual T cell, expressing a singular TCR, can discriminate as exquisitely among antigens as the most specific antibodies but also exhibit “degeneracy”: i.e., it can react with many disparate antigens (peptide-MHC complexes). An explanation for this duality (specificity and degeneracy) can be found in (i) the powerful amplifying signal transduction cascades that allow a T cell to respond to the stable engagement of very few TCR molecules, initially perhaps only one or two out of around 100,000 per cell, by their natural ligands (peptide-MHC complexes or epitopes on antigen-presenting cells—or APC) and (ii) the inverse relationship between TCR affinity for epitopes and epitope density (the number of copies of an epitope per APC). Older observations on the excess of total globulin production over specific antibody production in response to conventional immunization procedures suggest that B cells also exhibit degeneracy, as well as specificity. These views are developed against a backdrop describing how the author became interested in the immune system and has pursued that interest.

“…a concept of science drawn from … [textbooks] … is no more likely to fit the enterprise that produced them than an image of a national culture drawn from a tourist brochure.”

     Thomas Kuhn, Structure Of Scientific Revolutions
Origins and Functions of B-1 Cells with Notes on the Role of CD5
Authors: Berland Robert , Wortis Henry H.
Published: July 2002

Whether B-1a (CD5+) cells are a distinct lineage derived from committed fetal/neonatal precursors or arise from follicular B-2 cells in response to BCR ligation and other, unknown signals remains controversial. Recent evidence indicates that B-1a cells can derive from adult precursors expressing an appropriate specificity when the (self-) antigen is present. Antibody specificity determines whether a B cell expressing immunoglobulin transgenes has a B-2, B-1a or marginal zone (MZ) phenotype. MZ cells share many phenotypic characteristics of B-1 cells and, like them, appear to develop in response to T independent type 2 antigens. Because fetal-derived B cell progenitors fail to express terminal deoxynucleotidyl transferase (TdT) and for other reasons, they are likely to express a repertoire that allows selection into the B-1a population. As it is selected by self-antigen, the B-1 repertoire tends to be autoreactive. This potentially dangerous repertoire is also useful, as B-1 cells are essential for resistance to several pathogens and they play an important role in mucosal immunity. The CD5 molecule can function as a negative regulator of BCR signaling that may help prevent inappropriate activation of autoreactive B-1a cells.
PEROVSKITE THIN FILMS FOR HIGH-FREQUENCY CAPACITOR APPLICATIONS
Authors: Dimos D. , Mueller C. H.
Published: July 2002

▪ Abstract  Perovskite, ferroelectric and paraelectric, thin films exhibit outstanding dielectric properties, even at high frequencies (>1 GHz). This feature makes films such as (Ba,Sr)TiO3and Pb(Zr,Ti)O3ideally suited for a wide range of capacitor applications, particularly decoupling capacitors and tunable microwave capacitors; the latter application has been fueled by the recent explosion in wireless communications. The successful implementation of these materials as high-frequency dielectrics requires a detailed understanding of both their processing and materials properties.
SKUTTERUDITES: A Phonon-Glass-Electron Crystal Approach to Advanced Thermoelectric Energy Conversion Applications
Authors: Nolas G. S. , Morelli D. T. , Tritt Terry M.
Published: July 2002

▪ Abstract  Recently there has been a resurgence of research efforts related to the investigation of new and novel materials for small-scale thermoelectric refrigeration and power generation applications. These materials need to couple and optimize a variety of properties in order to exhibit the necessary figure of merit, i.e. the numerical expression that is commonly used to compare one potential thermoelectric material with another. The figure of merit is related to the coefficient of performance or efficiency of a particular device made from a material. The best thermoelectric material should possess thermal properties similar to that of a glass and electrical properties similar to that of a perfect single-crystal material, i.e. a poor thermal conductor and a good electrical conductor. Skutterudites are materials that appear to have the potential to fulfill such criteria. These materials exhibit many types of interesting properties. For example, skutterudites are members of a family of compounds we call open structure or cage-like, materials. When atoms are placed into the interstitial voids or cages of these materials, the lattice thermal conductivity can be substantially reduced compared with that of unfilled skutterudites. These compounds exhibit electrical properties ranging from that of low-temperature superconductors to narrow gap semiconductors.
Magnetocaloric Materials
Authors: Gschneidner K. A. , Pecharsky V. K.
Published: July 2002

▪ Abstract  In the last decade of the twentieth century there has been a significant increase in research on a more than 100-year old phenomenon—the magnetocaloric effect (MCE). As a result, many new materials with large MCEs (and many with lesser values) have been discovered, and a much better understanding of this magneto-thermal property has resulted. In this review we briefly discuss the principles of magnetic cooling (and heating); the measurement of the magnetocaloric properties by direct and indirect techniques; the special problems that can arise; and the MCE properties of the 4f lanthanide metals, their intra-lanthanide alloys and their compounds [including the giant MCE Gd5(SixGe1−x)4phases]; the 3d transition metals, their alloys and compounds; and mixed lanthanide-3d transition metal materials (including the La manganites).
Monoclonal Proteins and Renal Disease
Authors: Kyle Robert A.
Published: July 2002

Renal insufficiency, which is present initially in almost half of patients with multiple myeloma, usually results from myeloma kidney or hypercalcemia. Neither the class of light chain nor the isoelectric point plays an important role in kidney failure. Acute renal failure must be treated with appropriate fluids and with electrolytes and hemodialysis if necessary. Plasma exchange may be helpful, but has not been proven as such. The presence of a nephrotic syndrome and a monoclonal κ or λ light chain in the urine almost always indicates primary amyloidosis (AL) or light-chain deposition disease. Amyloid fibrils must be distinguished from the fibrils of immunotactoid glomerulopathy.
RU486 (MIFEPRISTONE): Mechanisms of Action and Clinical Uses
Authors: Cadepond, PhD F. , Ulmann, MD, PhD A. , Baulieu, MD, PhD E.-E.
Published: July 2002

▪ Abstract  RU486 (mifepristone) has proved to be a remarkably active antiprogesterone and antiglucocorticosteroid agent in human beings. The mechanism of action involves the intracellular receptors of the antagonized hormones (progesterone and glucocorticosteroids). At the molecular level, the most important features are high binding affinity to the receptor, interaction of the phenylaminodimethyl group in the 11β-position with a specific region of the receptor binding pocket, and RU486-induced transconformation differences in the ligand-binding domain. These particularities have consequences at different steps of the receptor function as compared with agonists. However, the reasoning cannot be limited to the RU486-receptor interaction, and, for instance, there is the possibility of a switch from antagonistic property to agonist activity, depending on the intervention of other signaling pathways. It would be desirable to have derivatives with only one of the two antagonistic properties (antiprogestin, antiglucocorticosteroid) in spite of similarities between steroid structures, receptors involved, and responsive machineries in target cells. Clinically, the RU486-plus-prostaglandin method is ready to be used on a large scale and is close to being as convenient and safe as any medical method of abortion may be. The early use of RU486 as a contragestive as soon as a woman fears a pregnancy she does not want will help to defuse the abortion issue. Research should now be conducted to define an efficient and convenient contraceptive method with RU486 or other antiprogestins. The usefulness of RU486 for obstetric indications, including facilitation of difficult delivery, has to be assessed rapidly. Gynecologic trials, particularly in leiomyomata, should also be systematically continued. The very preliminary results obtained with tumors, including breast cancers, indicate that further studies are necessary.
THE DEVELOPMENT AND CLINICAL UTILITY OF THE TAXANE CLASS OF ANTIMICROTUBULE CHEMOTHERAPY AGENTS
Authors: Rowinsky, MD Eric K.
Published: July 2002

▪ Abstract  The taxane class of antimicrotubule anticancer agents is perhaps the most important addition to the chemotherapeutic armamentarium against cancer over the past several decades. After only a brief period, the taxanes have not only demonstrated a unique ability to palliate the symptoms of many types of advanced cancers, including carcinoma of the ovary, lung, head and neck, bladder, and esophagus, they have also demonstrated effectiveness in the initial therapy of earlier stages of cancer, a setting in which any new therapy is likely to make its greatest impact. The challenge now facing investigators is to develop strategies to maximize therapeutic benefits with the taxanes in the early stages, as well as the advanced stages, of many cancers. This review describes the preclinical features and clinical results of the two major taxanes, paclitaxel (Taxol®, Bristol-Myers Squibb) and docetaxel (Taxotere®, Rhone-Poulenc Rhorer).
Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Authors: Ershler William B. , Keller Evan T.
Published: July 2002

Interleukin-6 (IL-6) is a proinflammatory cytokine that is normally tightly regulated and expressed at low levels, except during infection, trauma, or other stress. Among several factors that down-regulate IL-6 gene expression are estrogen and testosterone. After menopause or andropause, IL-6 levels are elevated, even in the absence of infection, trauma, or stress. IL-6 is a potent mediator of inflammatory processes, and it has been proposed that the age-associated increase in IL-6 accounts for certain of the phenotypic changes of advanced age, particularly those that resemble chronic inflammatory disease [decreased lean body mass, osteopenia, low-grade anemia, decreased serum albumin and cholesterol, and increased inflammatory proteins such as C-reactive protein (CRP) and serum amyloid A]. Furthermore, the age-associated rise in IL-6 has been linked to lymphoproliferative disorders, multiple myeloma, osteoporosis, and Alzheimer’s disease. This overview discusses the data relating IL-6 to age-associated diseases and to frailty. Like the syndrome of inappropriate antidiuretic hormone, it is possible that certain clinically important late-life changes are due to an inappropriate presence of IL-6.
CELL-CELL COMMUNICATION IN GRAM-POSITIVE BACTERIA
Authors: Dunny Gary M. , Leonard Bettina A. B.
Published: July 2002

▪ Abstract  In gram-positive bacteria, many important processes are controlled by cell-to-cell communication, which is mediated by extracellular signal molecules produced by the bacteria. Most of these signaling molecules are peptides or modified peptides. Signal processing, in most cases, involves either transduction across the cytoplasmic membrane or import of the signal and subsequent interaction with intracellular effectors. Concentrations of signal in the nanomolar range or below are frequently sufficient for biological activity. The microbial processes controlled by extracellular signaling include the expression of virulence factors, the expression of gene transfer functions, and the production of antibiotics.
NEW PERSPECTIVES ON MICROBIAL DEHALOGENATION OF CHLORINATED SOLVENTS: Insights from the Field
Authors: Lee M. D. , Odom J. M. , Buchanan Jr R. J.
Published: July 2002

▪ Abstract  A variety of microbial dechlorination mechanisms have been demonstrated in laboratory microcosms, pure cultures, and in situ sedimentary environments. New perspectives on in situ processes from these efforts allow the design of more realistic bioremediation strategies that complement natural processes regardless of whether the strategy used is one of engineered accelerated bioremediation or natural attenuation. Since 1994 the scientific community has acquired considerable knowledge regarding natural attenuation of organochlorine compounds. Natural attenuation of chlorinated solvents has been documented at a number of field sites. Reductive dechlorination driven by co-contaminants or naturally occurring organics as substrates in combination with aerobic or co-metabolic degradation contains certain chlorinated solvent plumes. Although natural attenuation is not a panacea, at sites where it is applicable, it offers a scientifically sound, cost-effective method to remediate groundwater contaminated with chlorinated solvents.
AGING IN SACCHAROMYCES CEREVISIAE
Authors: Sinclair David , Mills Kevin , Guarente Leonard
Published: July 2002

▪ Abstract  The budding yeast Saccharomyces cerevisiae divides asymmetrically, giving rise to a mother cell and a smaller daughter cell. Individual mother cells produce a finite number of daughter cells before senescing, undergoing characteristic changes as they age such as a slower cell cycle and sterility. The average life span is fixed for a given strain, implying that yeast aging has a strong genetic component. Genes that determine yeast longevity have highlighted the importance of such processes as cAMP metabolism, epigenetic silencing, and genome stability. The recent finding that yeast aging is caused, in part, by the accumulation of circular rDNA molecules has unified many seemingly disparate observations.
Transformation of Leukocytes byTheileria parvaandT. annulata
Authors: Dobbelaere Dirk , Heussler Volker
Published: July 2002

▪ Abstract  Theileria parva and T. annulata provide intriguing models for the study of parasite-host interactions. Both parasites possess the unique property of being able to transform the cells they infect; T. parva transforms T and B cells, whereas T. annulata affects B cells and monocytes/macrophages. Parasitized cells do not require antigenic stimulation or exogenous growth factors and acquire the ability to proliferate continuously. In vivo, parasitized cells undergo clonal expansion and infiltrate both lymphoid and non-lymphoid tissues of the infected host. Theileria-induced transformation is entirely reversible and is accompanied by the expression of a wide range of different lymphokines and cytokines, some of which may contribute to proliferation or may enhance spread and survival of the parasitized cell in the host. The presence of the parasite in the host-cell cytoplasm modulates the state of activation of a number of signal transduction pathways. This, in turn, leads to the activation of transcription factors, including nuclear factor-κB, which appear to be essential for the survival of Theileria-transformed T cells.
Poles Apart: Biodiversity and Biogeography of Sea Ice Bacteria
Authors: Staley James T. , Gosink John J.
Published: July 2002

▪ Abstract  This review introduces the subjects of bacterial biodiversity and biogeography. Studies of biogeography are important for understanding biodiversity, the occurrence of threatened species, and the ecological role of free-living and symbiotic prokaryotes. A set of postulates is proposed for biogeography as a guide to determining whether prokaryotes are “cosmopolitan” (found in more than one geographic location on Earth) or candidate endemic species. The term “geovar” is coined to define a geographical variety of prokaryote that is restricted to one area on Earth or one host species. This review discusses sea ice bacteriology as a test case for examining bacterial diversity and biogeography. Approximately 7% of Earth's surface is covered by sea ice, which is colonized principally by psychrophilic microorganisms. This extensive community of microorganisms, referred to as the sea ice microbial community (SIMCO), contains algae (mostly diatoms), protozoa, and bacteria. Recent investigations indicate that the sea ice bacteria fall into four major phylogenetic groups: the proteobacteria, the Cytophaga-Flavobacterium-Bacteroides (CFB) group, and the high and low mol percent gram-positive bacteria. Archaea associated with sea ice communities have also been reported. Several novel bacterial genera and species have been discovered, including Polaromonas, Polaribacter, Psychroflexus, Gelidibacter, and Octadecabacter; many others await study. Some of the gram-negative sea ice bacteria have among the lowest maximum temperatures for growth known, <10°C for some strains. The polar sea ice environment is an ideal habitat for studying microbial biogeography because of the dispersal issues involved. Dispersal between poles is problematic because of the long distances and the difficulty of transporting psychrophilic bacteria across the equator. Studies to date indicate that members of some genera occur at both poles; however, cosmopolitan species have not yet been discovered. Additional research on polar sea ice bacteria is needed to resolve this issue and extend our understanding of its microbial diversity.
Biofilm Formation as Microbial Development
Authors: O'Toole George , Kaplan Heidi B. , Kolter Roberto
Published: July 2002

▪ Abstract  Biofilms can be defined as communities of microorganisms attached to a surface. It is clear that microorganisms undergo profound changes during their transition from planktonic (free-swimming) organisms to cells that are part of a complex, surface-attached community. These changes are reflected in the new phenotypic characteristics developed by biofilm bacteria and occur in response to a variety of environmental signals. Recent genetic and molecular approaches used to study bacterial and fungal biofilms have identified genes and regulatory circuits important for initial cell-surface interactions, biofilm maturation, and the return of biofilm microorganisms to a planktonic mode of growth. Studies to date suggest that the planktonic-biofilm transition is a complex and highly regulated process. The results reviewed in this article indicate that the formation of biofilms serves as a new model system for the study of microbial development.
THE SPECIFICATION OF DORSAL CELL FATES IN THE VERTEBRATE CENTRAL NERVOUS SYSTEM
Authors: Lee Kevin J. , Jessell Thomas M.
Published: July 2002

▪ Abstract  The generation of distinct classes of neurons at defined positions within the developing vertebrate nervous system depends on inductive signals provided by local cell groups that act as organizing centers. Genetic and embryological studies have begun to elucidate the processes that control the pattern and identity of neuronal cell types. Here we discuss the cellular interactions and molecular mechanisms that direct neuronal cell fates in the dorsal half of the vertebrate central nervous system. The specification of dorsal neuronal cell fates appears to depend on a cascade of inductive signals initiated by cells of the epidermal ectoderm that flank the neural plate and propagated by roof plate cells within the neural tube. Members of the transforming growth factor−β(TGFβ) family of secreted proteins have a prominent role in mediating these dorsalizing signals. Additional signals involving members of the Wnt and fibroblast growth factor (FGF) families may also contribute to the proliferation and differentiation of dorsal neuronal cell types.
Neurodegenerative Tauopathies
Authors: Lee Virginia M-Y , Goedert Michel , Trojanowski John Q
Published: July 2002

▪ Abstract  The defining neuropathological characteristics of Alzheimer's disease are abundant filamentous tau lesions and deposits of fibrillar amyloid β peptides. Prominent filamentous tau inclusions and brain degeneration in the absence of β-amyloid deposits are also hallmarks of neurodegenerative tauopathies exemplified by sporadic corticobasal degeneration, progressive supranuclear palsy, and Pick's disease, as well as by hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Because multiple tau gene mutations are pathogenic for FTDP-17 and tau polymorphisms appear to be genetic risk factors for sporadic progressive supranuclear palsy and corticobasal degeneration, tau abnormalities are linked directly to the etiology and pathogenesis of neurodegenerative disease. Indeed, emerging data support the hypothesis that different tau gene mutations are pathogenic because they impair tau functions, promote tau fibrillization, or perturb tau gene splicing, thereby leading to formation of biochemically and structurally distinct aggregates of tau. Nonetheless, different members of the same kindred often exhibit diverse FTDP-17 syndromes, which suggests that additional genetic or epigenetic factors influence the phenotypic manifestations of neurodegenerative tauopathies. Although these and other hypothetical mechanisms of neurodegenerative tauopathies remain to be tested and validated, transgenic models are increasingly available for this purpose, and they will accelerate discovery of more effective therapies for neurodegenerative tauopathies and related disorders, including Alzheimer's disease.
Synaptic Modification by Correlated Activity: Hebb's Postulate Revisited
Authors: Bi Guo-qiang , Poo Mu-ming
Published: July 2002

▪ Abstract  Correlated spiking of pre- and postsynaptic neurons can result in strengthening or weakening of synapses, depending on the temporal order of spiking. Recent findings indicate that there are narrow and cell type–specific temporal windows for such synaptic modification and that the generally accepted input- (or synapse-) specific rule for modification appears not to be strictly adhered to. Spike timing–dependent modifications, together with selective spread of synaptic changes, provide a set of cellular mechanisms that are likely to be important for the development and functioning of neural networks.

When an axon of cell A is near enough to excite cell B or repeatedly or consistently takes part in firing it, some growth or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased.      Donald Hebb (1949)
MICRONUTRIENT MALNUTRITION: Policies and Programs for Control and Their Implications
Authors: Underwood Barbara A. , Smitasiri Suttilak
Published: July 2002

▪ Abstract  Global progress in social and economic development is occurring, although slowly, in the most needy parts of the nonindustrialized world, where nutritional deficiencies, including micronutrients, remain significant public health problems. Until empowering benefits accrue from development spin-offs, policy guidance for purposeful public health actions can help reduce the unconscionable toll on health and quality of life from micronutrient malnutrition and can interrupt its intergenerational debilitating effects on national development. Narrowly focused control programs including homestead production, plant breeding, fortification, and supplementation are in effect, but in general, they have not been holistically planned and integrated into overall development programs. Such integration is needed to ensure sustainability into the next century. A new paradigm is needed, including a new way of thinking by nutrition scientists and program implementers that includes partnerships with the poor in all aspects of program planning and implementation.
NUTRITIONALMANAGEMENT OFMAINTENANCEDIALYSISPATIENTS: Why Aren't We Doing Better?
Authors: Mehrotra Rajnish , Kopple Joel D
Published: July 2002

▪ Abstract  About 40% of patients undergoing maintenance dialysis suffer from varying degrees of protein-energy malnutrition. This is a problem of substantial importance because many measures of nutritional status correlate with the risk of morbidity and mortality. There are many causes of protein-energy malnutrition in maintenance dialysis patients. Evidence indicates that nutritional decline begins even when the reduction in glomerular filtration rate is modest, and it is likely that the observed decrease in dietary protein and energy intake plays an important role. The nutrient intake of patients receiving maintenance dialysis also is often inadequate, and several lines of evidence suggest that toxins that accumulate with renal failure suppress appetite and contribute to nutritional decline once patients are on maintenance dialysis. Recent epidemiologic studies have suggested that both increased serum levels of leptin and inflammation may reduce nutrient intake and contribute to the development of protein-energy malnutrition. It is likely that associated illnesses, which are highly prevalent, contribute to malnutrition in maintenance dialysis patients. Recent data from the United States Renal Data System registry suggest that in the United States, the mortality rate of dialysis patients is improving. However, it remains high. We offer suggestions for predialysis and dialysis care of these patients that can result in improvement in their nutritional status. Whether this improvement will result in a decrease in patient morbidity and mortality is unknown.
NUTRITIONAL IMPACT OF INTESTINAL HELMINTHIASIS DURING THE HUMAN LIFE CYCLE
Authors: Crompton D. W. T. , Nesheim M. C.
Published: July 2002

▪ Abstract  Poor people in developing countries endure the burden of disease caused by four common species of soil-transmitted nematode that inhabit the gastrointestinal tract. Disease accompanying these infections is manifested mainly as nutritional disturbance, with the differing infections having their deleterious effects at different phases during the human life cycle. Reduced food intake, impaired digestion, malabsorption, and poor growth rate are frequently observed in children suffering from ascariasis and trichuriasis. Poor iron status and iron deficiency anemia are the hallmarks of hookworm disease. The course and outcome of pregnancy, growth, and development during childhood and the extent of worker productivity are diminished during hookworm disease. Less is known about the impact of these infections in children under 2 years of age. The severity of disease caused by soil-transmitted nematodes has consistently been found to depend on the number of worms present per person. Cost-effective measures based on highly efficacious anthelminthic drugs are now available to reduce and control disease caused by these infections.
SCANNING TUNNELING AND ATOMIC FORCE MICROSCOPY PROBES OF SELF-ASSEMBLED, PHYSISORBED MONOLAYERS: Peeking at the Peaks
Authors: Giancarlo and Leanna C. , Flynn George W.
Published: July 2002

▪ Abstract  The imaging and control of self-assembled, physisorbed monolayers have been the subject of numerous scanning tunneling microscopy and atomic force microscopy investigations. The successful interpretation of the structures observed in scanning probe images of molecules self-assembled at liquid-solid and gas-solid interfaces has benefited greatly from recent experimental and theoretical work. These studies are converging on a general tunneling mechanism that accounts for the images of weakly bound, insulating adsorbates. Experiments in which the dynamical behavior of these monolayers has been monitored as a function of time both statically and after the introduction of an external perturbation are described, and novel studies of the selective control of monolayer structure that make use of internal and external electric fields, photons, and solvent coadsorption are reviewed.
STRUCTURE AND BONDING OF MOLECULES AT AQUEOUS SURFACES
Authors: Richmond GL
Published: July 2002

▪ Abstract  Significant advances toward understanding the structure of aqueous surfaces on a molecular level have been made in recent years. This review focuses on the recent contributions of surface vibrational sum frequency spectroscopy (VSFS) to this field of study. An overview of recent VSFS studies of the molecular structure and orientation of molecules at the vapor-water interface and the interface between water and an immiscible organic liquid is presented, with particular emphasis on studies that compare the molecular properties and adsorbate behavior at these two different but related interfaces. This discussion is preceded by a general introduction to VSFS studies at aqueous surfaces and a description of the fundamental principles underlying the technique.
CHEMICAL ACTIVATORS OF SENSORY NEURONS
Authors: Wood John N. , Docherty Reginald
Published: July 2002

▪ Abstract  Chemical activation of sensory neurons plays an important role in the somatosensory system. The actions of both endogenous mediators such as excitatory amino acids, acetylcholine, bradykinin, and ATP, as well as selective exogenous activators of nociceptive sensory neurons are reviewed. The physiological significance of these mediators in both nociception and other types of sensation are discussed.
Ventilatory Responses to Changes in Temperature in Mammals and Other Vertebrates
Authors: Mortola Jacopo P. , Frappell Peter B.
Published: July 2002

▪ Abstract  This article reviews the relationship between pulmonary ventilation (v̇e) and metabolic rate (oxygen consumption) during changes in ambient temperature. The main focus is on mammals, although for comparative purposes the v̇e responses of ectothermic vertebrates are also discussed. First, the effects of temperature on pulmonary mechanics, chemoreceptors, and airway receptors are summarized. Then we review the main v̇e responses to cold and warm stimuli and their interaction with exercise, hypoxia, or hypercapnia. In these cases, mammals attempt to maintain both oxygenation and body temperature, although conflicts can arise because of the respiratory heat loss associated with the increase in ventilation. Finally, we consider the v̇e responses of mammals when body temperature changes, as during torpor, fever, sleep, and hypothermia. In ectotherms, during changes in temperature, v̇e control becomes part of a general strategy to maintain constant relative alkalinity and ensure a constancy of pH-dependent protein functions (alphastat regulation). In mammals on the other hand, v̇e control is aimed to balance metabolic needs with homeothermy. Therefore, alphastat regulation in mammals seems to have a low priority, and it may be adopted only in exceptional cases.
Evolution and Physiological Roles of Phosphagen Systems
Authors: Ellington W Ross
Published: July 2002

▪ Abstract  Phosphagens are phosphorylated guanidino compounds that are linked to energy state and ATP hydrolysis by corresponding phosphagen kinase reactions: phosphagen + MgADP + H+↔ guanidine acceptor + MgATP. Eight different phosphagens (and corresponding phosphagen kinases) are found in the animal kingdom distributed along distinct phylogenetic lines. By far, the creatine phosphate/creatine kinase (CP/CK) system, which is found in the vertebrates and is widely distributed throughout the lower chordates and invertebrates, is the most extensively studied phosphagen system. Phosphagen kinase reactions function in temporal ATP buffering, in regulating inorganic phosphate (Pi) levels, which impacts glycogenolysis and proton buffering, and in intracellular energy transport. Phosphagen kinase reactions show differences in thermodynamic poise, and the phosphagens themselves differ in terms of certain physical properties including intrinsic diffusivity. This review evaluates the distribution of phosphagen systems and tissue-specific expression of certain phosphagens in an evolutionary and functional context. The role of phosphagens in regulation of intracellular Pi levels likely evolved early. Thermodynamic poise of the phosphagen kinase reaction profoundly impacts this capacity. Furthermore, it is hypothesized that the capacity for intracellular targeting of CK evolved early as a means of facilitating energy transport in highly polarized cells and was subsequently exploited for temporal ATP buffering and dynamic roles in metabolic regulation in cells displaying high and variable rates of aerobic energy production.
Epithelial Sodium Channel and the Control of Sodium Balance: Interaction Between Genetic and Environmental Factors
Authors: Rossier Bernard C. , Pradervand Sylvain , Schild Laurent , Hummler Edith
Published: July 2002

▪ Abstract  The epithelial sodium channel (ENaC) expressed in aldosterone-responsive epithelial cells of the kidney and colon plays a critical role in the control of sodium balance, blood volume, and blood pressure. In lung, ENaC has a distinct role in controlling the ionic composition of the air-liquid interface and thus the rate of mucociliary transport. Loss-of-function mutations in ENaC cause a severe salt-wasting syndrome in human pseudohypoaldosteronism type 1 (PHA-1). Gain-of-function mutations in ENaC β and γ subunits cause pseudoaldosteronism (Liddle's syndrome), a severe form of salt-sensitive hypertension. This review discusses genetically defined forms of a salt sensitivity and salt resistance in human monogenic diseases and in animal models mimicking PHA-1 or Liddle's syndrome. The complex interaction between genetic factors (ENaC mutations) and the risk factor (salt intake) can now be studied experimentally. The role of single-nucleotide polymorphisms (SNPs) in determining salt sensitivity or salt resistance in general populations is one of the main challenges of the post-genomic era.
Genetic Diseases of Acid-Base Transporters
Authors: Alper Seth L.
Published: July 2002

▪ Abstract  Genetic disorders of acid-base transporters involve plasmalemmal and organellar transporters of H+, HCO3−, and Cl−. Autosomal-dominant and -recessive forms of distal renal tubular acidosis (dRTA) are caused by mutations in ion transporters of the acid-secreting Type A intercalated cell of the renal collecting duct. These include the AE1 Cl−/HCO3− exchanger of the basolateral membrane and at least two subunits of the apical membrane vacuolar (v)H+-ATPase, the V1 subunit B1 (associated with deafness) and the V0 subunit a4. Recessive proximal RTA with ocular disease arises from mutations in the electrogenic Na+-bicarbonate cotransporter NBC1 of the proximal tubular cell basolateral membrane. Recessive mixed proximal-distal RTA accompanied by osteopetrosis and mental retardation is associated with mutations in cytoplasmic carbonic anhydrase II. The metabolic alkalosis of congenital chloride-losing diarrhea is caused by mutations in the DRA Cl−/HCO3− exchanger of the ileocolonic apical membrane. Recessive osteopetrosis is caused by deficient osteoclast acid secretion across the ruffled border lacunar membrane, the result of mutations in the vH+-ATPase V0 subunit or in the CLC-7 Cl− channel. X-linked nephrolithiasis and engineered deficiencies in some other CLC Cl− channels are thought to represent defects of organellar acidification. Study of acid-base transport disease-associated mutations should enhance our understanding of protein structure-function relationships and their impact on the physiology of cell, tissue, and organism.
HEALTH PSYCHOLOGY: Psychological Factors and Physical Disease from the Perspective of Human Psychoneuroimmunology
Authors: Cohen Sheldon , Herbert Tracy B.
Published: July 2002

▪ Abstract  This review addresses the importance of studies of human psychoneuroimmunology in understanding the role of psychological factors in physical illness. First, it provides psychologically and biologically plausible explanations for how psychological factors might influence immunity and immune system–mediated disease. Second, it covers substantial evidence that factors such as stress, negative affect, clinical depression, social support, and repression/denial can influence both cellular and humoral indicators of immune status and function. Third, at least in the case of the less serious infectious diseases (colds, influenza, herpes), it considers consistent and convincing evidence of links between stress and negative affect and disease onset and progression. Although still early in its development, research also suggests a role of psychological factors in autoimmune diseases. Evidence for effects of stress, depression, and repression/denial on onset and progression of AIDS and cancer is less consistent and inconclusive, possibly owing to methodological limitations inherent in studying these complex illnesses, or because psychological influences on immunity are not of the magnitude or type necessary to alter the body's response in these cases. What is missing in this literature, however, is strong evidence that the associations between psychological factors and disease that do exist are attributable to immune changes.
SURVEY RESEARCH
Authors: Krosnick Jon A.
Published: July 2002

▪ Abstract  For the first time in decades, conventional wisdom about survey methodology is being challenged on many fronts. The insights gained can not only help psychologists do their research better but also provide useful insights into the basics of social interaction and cognition. This chapter reviews some of the many recent advances in the literature, including the following: New findings challenge a long-standing prejudice against studies with low response rates; innovative techniques for pretesting questionnaires offer opportunities for improving measurement validity; surprising effects of the verbal labels put on rating scale points have been identified, suggesting optimal approaches to scale labeling; respondents interpret questions on the basis of the norms of everyday conversation, so violations of those conventions introduce error; some measurement error thought to have been attributable to social desirability response bias now appears to be due to other factors instead, thus encouraging different approaches to fixing such problems; and a new theory of satisficing in questionnaire responding offers parsimonious explanations for a range of response patterns long recognized by psycholo-gists and survey researchers but previously not well understood.
Depression: Perspectives from Affective Neuroscience
Authors: Davidson Richard J. , Pizzagalli Diego , Nitschke Jack B. , Putnam Katherine
Published: July 2002

▪ Abstract  Depression is a disorder of the representation and regulation of mood and emotion. The circuitry underlying the representation and regulation of normal emotion and mood is reviewed, including studies at the animal level, human lesion studies, and human brain imaging studies. This corpus of data is used to construct a model of the ways in which affect can become disordered in depression. Research on the prefrontal cortex, anterior cingulate, hippocampus, and amygdala is reviewed and abnormalities in the structure and function of these different regions in depression is considered. The review concludes with proposals for the specific types of processing abnormalities that result from dysfunctions in different parts of this circuitry and offers suggestions for the major themes upon which future research in this area should be focused.
ECONOMETRICS IN OUTCOMES RESEARCH: The Use of Instrumental Variables
Authors: Newhouse Joseph P. , McClellan Mark
Published: July 2002

▪ Abstract  We describe an econometric technique, instrumental variables, that can be useful in estimating the effectiveness of clinical treatments in situations when a controlled trial has not or cannot be done. This technique relies upon the existence of one or more variables that induce substantial variation in the treatment variable but have no direct effect on the outcome variable of interest. We illustrate the use of the technique with an application to aggressive treatment of acute myocardial infarction in the elderly.