bluuebunny/crossref_metadata_2025 huggingface dataset:
The accuracy of perception of a pinch grip force in older adults
Authors: De Serres Sophie J , Fang Nathan Z
Published: November 2004

The fact that humans can execute accurate movements and generate precise muscle forces is very important for hand function. Target-tracking tasks or target-matching tasks are often executed under combined visual and somatosensory feedback. When visual feedback is removed, subjects have to depend on their perception of force. The objective of the present study was to estimate the effects of aging on the perception of a pinch force produced by the thumb and index finger. In a first set of trials, young (n = 12, age = 25.3 ± 2.4 years) and elderly (n = 12, age = 71.5 ± 3.3 years) healthy individuals were asked to reproduce pinch forces which were equivalent to 5%, 20%, and 40% of their maximal pinch force (MPF). Prior to the execution of these trials, the subjects were familiarized with the force levels by matching targets displayed on a screen. They were then asked to reproduce each of these forces without any visual or verbal feedback. The results showed a larger error in the reproduced force for the elderly subjects when compared with the young adults. However, this larger error was mainly due to an initial overshoot in the force to be reproduced, followed by a gradual decrease towards the appropriate force. This transient overshoot was rarely seen in the performance of the younger subjects. In a second set of trials, the same subjects were asked to produce a pinch force of 5%, 20%, and 40% of MPF with 1 hand using visual feedback. They were also instructed to simultaneously apply a comparable pinch force with the other hand (without any feedback). For both young and older adults, the pinch forces produced by the 2 hands were the same. In addition, in both blocks of trials, hand dominance had no effects on the performance for all subjects. These results suggest that normal aging affects the production of force based on sensorimotor memory rather more than it affects comparative outputs from central descending commands.Key words: prehension, isometric force, aging, tactile feedback.
Immunofluorescence revealed the presence of NHE-1 in the nuclear membranes of rat cardiomyocytes and isolated nuclei of human, rabbit, and rat aortic and liver tissues
Authors: Bkaily Ghassan , Nader Moni , Avedanian Levon , Jacques Danielle , Perrault Claudine , Abdel-Samad Dima , D'Orléans-Juste Pedro , Gobeil Fernand , Hazzouri Khaled M
Published: November 2004

Using immunofluorescence and 3-dimensional confocal microscopy techniques, the present study was designed to verify if NHE-1 is present at the level of the nuclear membrane in cells that are known to express this type of exchanger. Nuclei were isolated from aortic tissues of adult human, rabbit, and rats, as well as from liver tissues of human fetus, and adult rabbit and rat. In addition, cultured ventricular cardiomyocytes were isolated from 2-week-old rat. Our results showed the presence of NHE-1 in isolated nuclei of aortic vascular smooth muscle and liver of human, rabbit, and rat. NHE-1 seems to be distributed throughout the isolated nucleus and more particularly at the level of the nuclear membranes. The relative fluorescence density of NHE-1 was significantly higher (p < 0.05) in isolated liver nuclei of human, when compared with those of rabbit and rat. However, in isolated nuclei of aortic vascular smooth muscle, the relative fluorescence density of NHE-1 was significantly (p < 0.001) higher in the rabbit when compared with human and rat. In cultured rat ventricular cardiomyocytes, NHE-1 fluorescent labeling could be easily seen throughout the cell, including the nucleus, and more particularly at both the sarcolemma and the nuclear membranes. In rat cardiomyocytes, the relative fluorescence density of NHE-1 of the sarcolemma membrane, including the cytosol, was significantly lower than that of the whole nucleus (including the nuclear envelope membranes). In conclusion, our results showed that NHE-1 is present at the nuclear membranes and in the nucleoplasm and its distribution and density may depend on cell type and species used. These results suggest that nuclear membranes' NHE-1 may play a role in the modulation of intranuclear pH.Key words: NHE-1, heart, aorta, liver, nuclear membranes, nucleus.
KNOTS IN THE NON-ABELIAN CHERN–SIMONS THEORY
Authors: ZHANG PENG-MING , DUAN YI-SHI , LIU XIN
Published: November 2004

We employ a spinor decomposition of SU (2) connection to study the Chern–Simons form. Our results show that the SU (2) Chern–Simons action yields the link invariants. Then the structure of the knots is discussed with the ϕ-mapping theory.
SOME OPTIMAL STOCHASTIC CONTROL PROBLEMS IN NEUROSCIENCE — A REVIEW
Authors: FENG JIANFENG , CHEN XIAOJIANG , TUCKWELL HENRY C. , VASILAKI ELENI
Published: November 2004

Nervous systems are probability machines and, as such, modeling their activities should incorporate stochastic processes. In this review, we present two examples of optimal stochastic control problems with an analytic methodology on how to find optimal signals. The first example deals with neuronal activity and the second example is concerned with a higher level task: arm movement. In both cases we find optimal signals for particular tasks and find our results in agreement with the experimental Fitts Law.
TEMPERATURE DEPENDENCE OF CARRIER MOBILITY IN EPITAXIAL THIN FILM La0.8Ca0.2MnO3/PbZr0.2Ti0.8O3 HETEROSTRUCTURE
Authors: ZHU M.
Published: November 2004

Temperature dependences of the carrier mobility and charge density are studied for the MOS-FET epitaxial thin film La 0.8 Ca 0.2 MnO 3/ PbZr 0.2 Ti 0.8 O 3 heterostructure both above and below the metal insulator transition temperature. The behaviors of the mobility at low and high electric fields are found to be quite different from each other. Our results demonstrate that the change of channel thickness at high electric fields has a significant influence on the carrier mobility.
ANALYSIS OF MELTING FOR ALKALI EARTH AND ALKALI OXIDES BASED ON THE DIFFUSIONAL FORCE THEORY
Authors: LIU QUAN , CHEN LI-RONG
Published: November 2004

An analysis of the melting alkali earth and alkali oxides is presented using the concept of diffusional force. The calculations are performed by developing an ionic model based on Harrison's quantum mechanical treatment of overlap repulsive potential which takes into account the interactions up to second neighbors. Van der Waals dipole–dipole and dipole–quadrupole interactions calculated by more accurate methods are also included in the model. Using the formula by Fang, derived on the basis of thermodynamic analysis, the values of interionic distances for 8 alkali earth and alkali oxides at melting have been obtained. A simple model for melting is developed based on the diffusional force models. The values of Tm thus obtained are found to show fairly good agreement with experimental values of melting temperatures.
A MOVING RUBIDIUM ATOM INTERACTING WITH A SINGLE MODE CAVITY FIELD IN THE PRESENCE OF KERR MEDIUM
Authors: ZAIT R. A. , ABD EL-WAHAB N. H.
Published: November 2004

We study the interaction between a moving four-level rubidium atom and a single mode cavity field in the presence of a nonlinear Kerr-like medium. We derive the basic equations of motion for the atomic system and show that it is exactly solvable in the rotating wave approximation. The momentum increment, the momentum diffusion and the quasi-probability distribution Q-function of this system are studied. We investigate numerically the influence of the Kerr medium on the evolution of the previous statistical properties in the exact resonant and nonresonant cases where the atom is initially in the ground state and the field is in a coherent state. It is found that the Kerr medium has an important effect on their evolutions. Finally, conclusions and discussion are given.
EDGE STATE IN ATOMIC HALL EFFECT
Authors: ZHAO BO , CHEN ZENG-BING
Published: November 2004

We study the edge state of atomic Hall fluids. It is described by a chiral 1D bosonic field theory and the atomic excitations are a type of bosonic Luttinger liquid. We investigate the dynamical property of edge state and propose an experiment to measure the topological number, which could be verified experimentally in future.
INVESTIGATION OF QUANTUM CHAOS IN THE PARAMETRIC DEPENDENT SYSTEM OF INTERACTING OSCILLATORS
Authors: CHOTORLISHVILI L. , TOKLIKISHVILI Z. , BOCHORISHVILI V. , SAGARADZE A.
Published: November 2004

The formation of chaos in the parametric dependent system of interacting oscillators for both classical and quantum cases has been investigated. The domain in which classical motion is chaotic is defined. It has been shown that for certain values of the parameters from this domain, the form of the classical power spectrum is in a good agreement with the quantum band profile. Local density of states is calculated. The range in which application of perturbation theory is correct has been defined.
OPTIONS WRITTEN ON STOCKS WITH KNOWN DIVIDENDS
Authors: EKSTRÖM ERIK , TYSK JOHAN
Published: November 2004

There are two common methods for pricing European call options on a stock with known dividends. The market practice is to use the Black–Scholes formula with the stock price reduced by the present value of the dividends. An alternative approach is to increase the strike price with the dividends compounded to expiry at the risk-free rate. These methods correspond to different stock price models and thus in general give different option prices. In the present paper we generalize these methods to time- and level-dependent volatilities and to arbitrary contract functions. We show, for convex contract functions and under very general conditions on the volatility, that the method which is market practice gives the lower option price. For call options and some other common contracts we find bounds for the difference between the two prices in the case of constant volatility.
COHERENT PORTFOLIO SEPARATION — INHERENT SYSTEMIC RISK?
Authors: FRAMSTAD NILS CHR.
Published: November 2004

A stylized market risk model is studied. It turns out that quantifying risk by quantile-VaR, coherent risk measures or other functionals that are positively homogeneous, has a consequence akin to assuming multi-normal returns, namely a two fund separation property. Heuristic arguments indicate that this may be a source of systemic risk to the financial industry.
Child Maltreatment
Authors: Cicchetti Dante , Toth Sheree L.
Published: November 2004

Child maltreatment exemplifies a toxic relational environment that poses significant risks for maladaptation across biological and psychological domains of development. Research on child maltreatment can inform developmental theory, but more importantly, it can enhance the quality of clinical, legal, and policy-making decisions for maltreated children. This chapter addresses definitional, epidemiological, and etiological aspects of child maltreatment. A developmental psychopathology perspective is directed toward the discussion of the psychological and neurobiological sequelae of child maltreatment. Implications for prevention, intervention, and social policy are discussed, and recommendations for future research are proffered.
ARE THE ALPS COLLAPSING?
Authors: Selverstone Jane
Published: November 2004

▪ Abstract  Orogenic collapse is a process that transfers gravitational potential energy from regions of high potential energy to regions of lower potential energy. This transfer is classically considered to be accomplished by extension in the orogenic core and by synchronous shortening in foreland regions of the orogen. Not all extensional features in collisional mountain belts need, however, reflect orogenic collapse. Normal faulting, thrust faulting, and strike-slip faulting are all active in different parts of the Alps today and reflect complex local responses to ongoing Europe-Adria convergence. The Western Alps is the only area today where extension and shortening radial to orogen trend occur synchronously and where orogenic collapse may be an important process. Elsewhere in the Alps, normal faults are oriented at a high angle to orogen trend and were primarily active in Oligocene and Miocene time. Most present-day activity in the Central and Eastern Alps is on strike-slip faults that are accommodating lateral extrusion of material rather than orogenic collapse.
Pollination Syndromes and Floral Specialization
Authors: Fenster Charles B. , Armbruster W. Scott , Wilson Paul , Dudash Michele R. , Thomson James D.
Published: November 2004

▪ Abstract  Floral evolution has often been associated with differences in pollination syndromes. Recently, this conceptual structure has been criticized on the grounds that flowers attract a broader spectrum of visitors than one might expect based on their syndromes and that flowers often diverge without excluding one type of pollinator in favor of another. Despite these criticisms, we show that pollination syndromes provide great utility in understanding the mechanisms of floral diversification. Our conclusions are based on the importance of organizing pollinators into functional groups according to presumed similarities in the selection pressures they exert. Furthermore, functional groups vary widely in their effectiveness as pollinators for particular plant species. Thus, although a plant may be visited by several functional groups, the relative selective pressures they exert will likely be very different. We discuss various methods of documenting selection on floral traits. Our review of the literature indicates overwhelming evidence that functional groups exert different selection pressures on floral traits. We also discuss the gaps in our knowledge of the mechanisms that underlie the evolution of pollination syndromes. In particular, we need more information about the relative importance of specific traits in pollination shifts, about what selective factors favor shifts between functional groups, about whether selection acts on traits independently or in combination, and about the role of history in pollination-syndrome evolution.
Predator-Induced Phenotypic Plasticity in Organisms with Complex Life Histories
Authors: Benard Michael F.
Published: November 2004

▪ Abstract  Predator-induced phenotypic plasticity is widespread in nature and includes variation in life history, morphology, and behavior. In organisms with complex life histories, predator-induced phenotypic plasticity in the larval period has been widely documented. Several models predict how organisms should alter their size at and time to metamorphosis in response to an increased risk of predation. A survey of empirical studies finds that these theoretical predictions are frequently met. However, no one model performs the best. Additionally, there are several results not predicted by any model. Predator-induced plasticity in metamorphic traits may be related to predator-induced changes in larval morphology and behavior. Predictions of predator effects on larval traits are generally met, except for direct costs of predator-induced morphological phenotypes. Future work should incorporate more detailed studies of growth rate, morphology, and behavior during the larval period, as well as studies of size-specific mortality rates in the presence and absence of predators.
The New View of Animal Phylogeny
Authors: Halanych Kenneth M.
Published: November 2004

▪ Abstract  Molecular tools have profoundly rearranged our understanding of metazoan phylogeny. Initially based on the nuclear small ribosomal subunit (SSU or 18S) gene, recent hypotheses have been corroborated by several sources of data (including the nuclear large ribosomal subunit, Hox genes, mitochondrial gene order, concatenated mitochondrial genes, and the myosin II heavy chain gene). Herein, the evidence supporting our current understanding is discussed on a clade by clade basis. Bilaterian animals consist of three clades: Deuterostomia, Lophotrochozoa, and Ecdysozoa. Each clade is supported by molecular and morphological data. Deuterostomia is smaller than traditionally recognized, consisting of hemichordates, echinoderms, chordates, and Xenoturbella (an enigmatic worm-like animal). Lophotrochozoa groups animals with a lophophore feeding apparatus (Brachiopoda, Bryozoa, and Phoronida) and trochophore larvae (e.g., annelids and mollusk), as well as several other recognized phyla (e.g., platyhelmin thes, sipunculans, nemerteans). Ecdysozoa comprises molting animals (e.g., arthropods, nematodes, tardigrades, priapulids), grouping together two major model organisms (Drosophila and Caenorhabditis) in the same lineage. Platyhelminthes do not appear to be monophyletic, with Acoelomorpha holding a basal position in Bilateria. Before the emergence of bilateral animals, sponges, ctenophorans, cnidarians, and placozoans split from the main animal lineage, but order of divergence is less than certain. Many questions persist concerning relationships within Ecdysozoa and Lophotrochozoa, poriferan monophyly, and the placement of many less-studied taxa (e.g., kinorhynchs, gastrotrichs, gnathostomulids, and entoprocts).
Application of Ecological Indicators
Authors: Niemi Gerald J. , McDonald Michael E.
Published: November 2004

▪ Abstract  Ecological indicators have widespread appeal to scientists, environmental managers, and the general public. Indicators have long been used to detect changes in nature, but the scientific maturation in indicator development primarily has occurred in the past 40 years. Currently, indicators are mainly used to assess the condition of the environment, as early-warning signals of ecological problems, and as barometers for trends in ecological resources. Use of ecological indicators requires clearly stated objectives; the recognition of spatial and tempor al scales; assessments of statistical variability, precision, and accuracy; linkages with specific stressors; and coupling with economic and social indicators. Legislatively mandated use of ecological indicators occurs in many countries worldwide and is included in international accords. As scientific advancements and innovation in the development and use of ecological indicators continue through applications of molecular biology, computer technology such as geographic information systems, data management such as bioinformatics, and remote sensing, our ability to apply ecological indicators to detect signals of environmental change will be substantially enhanced.
PHEROMONE-MEDIATED AGGREGATION IN NONSOCIAL ARTHROPODS: An Evolutionary Ecological Perspective
Authors: Wertheim Bregje , van Baalen Erik-Jan A. , Dicke Marcel , Vet Louise E.M.
Published: November 2004

▪ Abstract  Although the use of aggregation pheromones has been reported for hundreds of nonsocial arthropod species, the evolutionary ecological aspects of this behavior have received little attention. Despite the elaborate literature on mechanisms, robust data on costs and benefits of aggregation pheromones are scant. Existing literature indicates that, in contrast to the diversity of mechanisms, the ecological conditions in which aggregation pheromones are used are more alike. This points to a few general categories for costs and benefits of aggregation pheromones, and these are discussed. We subsequently review interspecific interactions that may be affected by the use of aggregation pheromones. We encounter a strikingly frequent association of aggregation pheromones with fungi and microorganisms and address cross-attraction by competitor species and exploitation by natural enemies. We show that aggregative behavior by individuals through the use of pheromones can profoundly affect ecological interactions and advocate further evolutionary and ecological investigations of pheromone-mediated aggregation.
FECAL RESIDUES OF VETERINARY PARASITICIDES: Nontarget Effects in the Pasture Environment
Authors: Floate Kevin D. , Wardhaugh Keith G. , Boxall Alistair B.A. , Sherratt Thomas N.
Published: November 2004

▪ Abstract  Residues of veterinary parasiticides in dung of treated livestock have nontarget effects on dung-breeding insects and dung degradation. Here, we review the nature and extent of these effects, examine the potential risks associated with different classes of chemicals, and describe how greater awareness of these nontarget effects has resulted in regulatory changes in the registration of veterinary products.
TYRAMINE AND OCTOPAMINE: Ruling Behavior and Metabolism
Authors: Roeder Thomas
Published: November 2004

▪ Abstract  Octopamine (OA) and tyramine (TA) are the invertebrate counterparts of the vertebrate adrenergic transmitters. They are decarboxylation products of the amino acid tyrosine, with TA as the biological precursor of OA. Nevertheless, both compounds are independent neurotransmitters that act through G protein–coupled receptors. OA modulates a plethora of behaviors and peripheral and sense organs, enabling the insect to respond correctly to external stimuli. Because these two phenolamines are the only biogenic amines whose physiological significance is presumably restricted to invertebrates, pharmacologists have focused their attention on the corresponding receptors, which are still believed to represent promising targets for new insecticides. Recent progress made on all levels of OA and TA research has enabled researchers to understand better the molecular events underlying the control of complex behaviors.
INVASIVE PHYTOPHAGOUS PESTS ARISING THROUGH A RECENT TROPICAL EVOLUTIONARY RADIATION: TheBactrocera dorsalisComplex of Fruit Flies
Authors: Clarke Anthony R. , Armstrong Karen F. , Carmichael Amy E. , Milne John R. , Raghu S. , Roderick George K. , Yeates David K.
Published: November 2004

▪ Abstract  The Bactrocera dorsalis complex of tropical fruit flies (Diptera: Tephritidae: Dacinae) contains 75 described species, largely endemic to Southeast Asia. Within the complex are a small number of polyphagous pests of international significance, including B. dorsalis sensu stricto, B. papayae, B. carambolae, and B. philippinensis. Most species within the complex were described in 1994 and since then substantial research has been undertaken in developing morphological and molecular diagnostic techniques for their recognition. Such techniques can now resolve most taxa adequately. Genetic evidence suggests that the complex has evolved in only the last few million years, and development of a phylogeny of the group is considered a high priority to provide a framework for future evolutionary and ecological studies. As model systems, mating studies on B. dorsalis s.s. and B. cacuminata have substantially advanced our understanding of insect use of plant-derived chemicals for mating, but such studies have not been applied to help resolve the limits of biological species within the complex. Although they are commonly regarded as major pests, there is little published evidence documenting economic losses caused by flies of the B. dorsalis complex. Quantification of economic losses caused by B. dorsalis complex species is urgently needed to prioritize research for quarantine and management. Although they have been documented as invaders, relatively little work has been done on the invasion biology of the complex and this is an area warranting further work.
THE GENETICS AND GENOMICS OF THE SILKWORM, BOMBYX MORI
Authors: Goldsmith Marian R. , Shimada Toru , Abe Hiroaki
Published: November 2004

▪ Abstract  We review progress in applying molecular genetic and genomic technologies to studies in the domesticated silkworm, Bombyx mori, highlighting its use as a model for Lepidoptera, and in sericulture and biotechnology. Dense molecular linkage maps are being integrated with classical linkage maps for positional cloning and marker-assisted selection. Classical mutations have been identified by a candidate gene approach. Cytogenetic and sequence analyses show that the W chromosome is composed largely of nested full-length long terminal repeat retrotransposons. Z-chromosome-linked sequences show a lack of dosage compensation. The downstream sex differentiation mechanism has been studied via the silkworm homolog of doublesex. Expressed sequence tagged databases have been used to discover Lepidoptera-specific genes, provide evidence for horizontal gene transfer, and construct microarrays. Physical maps using large-fragment bacterial artificial chromosome libraries have been constructed, and whole-genome shotgun sequencing is underway. Germline transformation and transient expression systems are well established and available for functional studies, high-level protein expression, and gene silencing via RNA interference.
Developmental Gene Amplification and Origin Regulation
Authors: Tower John
Published: November 2004

▪ Abstract  Developmentally regulated gene amplification serves to increase the number of templates for transcription, yielding greatly increased protein and/or RNA product for gene(s) at the amplified loci. It is observed with genes that are very actively transcribed and during narrow windows of developmental time where copious amounts of those particular gene products are required. Amplification results from repeated firing of origins at a few genomic loci, while the rest of the genome either does not replicate, or replicates to a lesser extent. As such, amplification is a striking exception to the once-and-only-once rule of DNA replication and may be informative as to that mechanism. Drosophila amplifies eggshell (chorion) genes in the follicle cells of the ovary to allow for rapid eggshell synthesis. Sciara amplifies multiple genes in larval salivary gland cells that encode proteins secreted in the saliva for the pupal case. Finally, Tetrahymena amplifies its rRNA genes several thousand-fold in the creation of the transcriptionally active macronucleus. Due to the ease of molecular and genetic analysis with these systems, the study of origin regulation has advanced rapidly. Comparisons reveal an evolutionarily conserved trans-regulatory apparatus and a similar organization of sequence-specific cis-regulatory replicator and origin elements. The studies indicate a regulatory role for chromatin structure and transcriptionally active genes near the origins.
DEVELOPMENT AND REGULATION OF CELL-MEDIATED IMMUNE RESPONSES TO THE BLOOD STAGES OF MALARIA: Implications for Vaccine Research
Authors: Good Michael F. , Xu Huji , Wykes Michelle , Engwerda Christian R.
Published: November 2004

▪ Abstract  The immune response to the malaria parasite is complex and poorly understood. Although antibodies and T cells can control parasite growth in model systems, natural immunity to malaria in regions of high endemicity takes several years to develop. Variation and polymorphism of antibody target antigens are known to impede immune responses, but these factors alone cannot account for the slow acquisition of immunity. In human and animal model systems, cell-mediated responses can control parasite growth effectively, but such responses are regulated by parasite load via direct effects on dendritic cells and possibly on T and B cells as well. Furthermore, high parasite load is associated with pathology, and cell-mediated responses may also harm the host. Inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, anemia, weight loss, and respiratory distress in malaria. Immunity without pathology requires rapid parasite clearance, effective regulation of the inflammatory antiparasite effects of cellular responses, and the eventual development of a repertoire of antibodies effective against multiple strains. Data suggest that this may be hastened by exposure to malaria antigens in low dose, leading to augmented cellular immunity and rapid parasite clearance.
Definition and Clinical Importance of Haplotypes
Authors: Crawford Dana C. , Nickerson Deborah A.
Published: November 2004

Advances in genotyping and sequencing technologies, coupled with the development of sophisticated statistical methods, have afforded investigators novel opportunities to define the role of sequence variation in the development of common human diseases. At the forefront of these investigations is the use of dense maps of single-nucleotide polymorphisms (SNPs) and the haplotypes derived from these polymorphisms. Here we review basic concepts of high-density genetic maps of SNPs and haplotypes and how they are typically generated and used in human genetic research. We also provide useful examples and tools available for researchers interested in incorporating haplotypes into their studies. Finally, we discuss the latest concepts for the analysis of haplotypes related to human disease, including haplotype blocks, the International HapMap Project, and the future directions of these resources.
G Protein Polymorphisms in Hypertension, Atherosclerosis, and Diabetes
Authors: Siffert Winfried
Published: November 2004

A common C825T polymorphism in the gene GNB3, which encodes the β3 subunit of heterotrimeric G proteins, was identified in cell lines from patients with hypertension. The 825T allele is associated with increased intracellular signal transduction. Many population-based and case-control studies in different ethnicities have investigated an association between this polymorphism and hypertension, obesity, and atherosclerosis. A critical assessment of published studies suggests that 825T allele carriers have an increased risk for hypertension combined with features of the metabolic syndrome, such as dyslipidemia, hypercholesterolemia, insulin resistance, and obesity. It is anticipated that this polymorphism will be used in clinical practice to better characterize hypertension and for individualized treatment regimens.
Management of Peripheral Vascular Disease
Authors: Baumgartner I. , Schainfeld R. , Graziani L.
Published: November 2004

The management of patients with peripheral arterial occlusive disease (PAD) has to be planned in the context of natural history, epidemiology, and apparent risk factors that predict deterioration. The ankle-brachial index to date has proved to be the most effective, accurate, and practical method of PAD detection. Given that PAD is a powerful indicator of systemic atherosclerosis and (independent of symptoms) is associated with an increased risk of myocardial infarction and stroke, as well as a six times greater likelihood of death, the prevalence and demographic distribution of measurable PAD becomes particularly relevant. Reliable information on interventions to confer symptom relief is much weaker and reflects discrepancies between published reports from centers of excellence and the experience of patients routinely treated in communities around the world. The impact of newer treatment modalities, such as complex endovascular procedures and therapeutic angiogenesis, has been a subject of recent controversy.
Atrial Fibrillation: Modern Concepts and Management
Authors: Agarwal Ashish , York Meghan , Kantharia Bharat K. , Ezekowitz Michael
Published: November 2004

Atrial fibrillation (AF) is a common cardiac arrhythmia responsible for significant morbidity and mortality. In recent years, progress has been made in determining the genetic abnormalities that may lead to AF. New trials have shown that rate control and anticoagulation are acceptable as a primary treatment strategy in many patients who have a high risk of recurrence. Newer and safer antiarrhythmics are now available. Pacemaker and implantable cardiac defibrillator technology is rapidly evolving and may play a significant role in future treatment and prevention of AF. Direct thrombin inhibitors are likely to add a user-friendly option to the current standard therapy for stroke prevention.
New Anticoagulant Therapy
Authors: Linkins Lori-Ann , Weitz Jeffrey I.
Published: November 2004

The development of new anticoagulants is expanding the list of drugs that can be used to prevent and treat venous and arterial thrombosis. New parenteral anticoagulants have been developed to overcome the limitations of heparin and low-molecular-weight heparin, whereas novel orally active anticoagulants have been designed to provide more streamlined therapy than vitamin K antagonists. This review identifies the molecular targets of new anticoagulants, describes the results of clinical trials, and provides clinical perspective on the opportunities for new anticoagulants.
EVALUATION OF DRUG-DRUG INTERACTION IN THE HEPATOBILIARY AND RENAL TRANSPORT OF DRUGS
Authors: Shitara Yoshihisa , Sato Hitoshi , Sugiyama Yuichi
Published: November 2004

▪ Abstract  Recent studies have revealed the import role played by transporters in the renal and hepatobiliary excretion of many drugs. These transporters exhibit a broad substrate specificity with a degree of overlap, suggesting the possibility of transporter-mediated drug-drug interactions with other substrates. This review is an overview of the roles of transporters and the possibility of transporter-mediated drug-drug interactions. Among the large number of transporters, we compare the Ki values of inhibitors for organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) and their therapeutic unbound concentrations. Among them, cephalosporins and probenecid have the potential to produce clinically relevant OAT-mediated drug-drug interactions, whereas cyclosporin A and rifampicin may trigger OATP-mediated ones. These drugs have been reported to cause drug-drug interactions in vivo with OATs or OATP substrates, suggesting the possibility of transporter-mediated drug-drug interactions. To avoid adverse consequences of such transporter-mediated drug-drug interactions, we need to be more aware of the role played by drug transporters as well as those caused by drug metabolizing enzymes.
SIGNALING NETWORKS IN LIVING CELLS
Authors: White Michael A. , Anderson Richard G.W.
Published: November 2004

▪ Abstract  Recent advances in cell signaling research suggest that multiple sets of signal transducing molecules are preorganized and sequestered in distinct compartments within the cell. These compartments are assembled and maintained by specific cellular machinery. The molecular ecology within a compartment creates an environment that favors the efficient and accurate integration of signaling information arriving from humoral, mechanical, and nutritional sources. The functional organization of these compartments suggests they are the location of signaling networks that naturally organize into hierarchical interconnected sets of molecules through their participation in different classes of interacting units. An important goal is to determine the contribution of the compartment to the function of these networks in living cells.
FORMATION AND TOXICITY OF ANESTHETIC DEGRADATION PRODUCTS
Authors: Anders M.W.
Published: November 2004

▪ Abstract  Toxic degradation products are formed from a range of old and modern anesthetic agents. The common element in the formation of degradation products is the reaction of the anesthetic agent with the bases in the carbon dioxide absorbents in the anesthesia circuit. This reaction results in the conversion of trichloroethylene to dichloroacetylene, halothane to 2-bromo-2-chloro-1,1-difluoroethylene, sevoflurane to 2-(fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (Compound A), and desflurane, isoflurane, and enflurane to carbon monoxide. Dichloroacetylene, 2-bromo-2-chloro-1,1-difluoroethylene, and Compound A form glutathione S-conjugates that undergo hydrolysis to cysteine S-conjugates and bioactivation of the cysteine S-conjugates by renal cysteine conjugate β-lyase to give nephrotoxic metabolites. The elucidation of the mechanisms of formation and bioactivation of degradation products has allowed for the safe use of anesthetics that may undergo degradation in the anesthesia circuit.
MOLECULAR MECHANISMS OF RESISTANCE IN ANTIMALARIAL CHEMOTHERAPY: The Unmet Challenge
Authors: Arav-Boger Ravit , Shapiro Theresa A.
Published: November 2004

▪ Abstract 

The enormous public health problem posed by malaria has been substantially worsened in recent years by the emergence and worldwide spread of drug-resistant parasites. The utility of two major therapies, chloroquine and the synergistic combination of pyrimethamine/sulfadoxine, is now seriously compromised. Although several genetic mechanisms have been described, the major source of drug resistance appears to be point mutations in protein target genes. Clinically significant resistance to these agents requires the accumulation of multiple mutations, which genetic studies of parasite populations suggest arise focally and sweep through the population. Efforts to circumvent resistance range from the use of combination therapy with existing agents to laboratory studies directed toward discovering novel targets and therapies.

The prevention and management of drug resistance are among the most important practical problems of tropical medicine and public health.

Leonard J. Bruce-Chwatt, 1972
NATURAL HEALTH PRODUCTS AND DRUG DISPOSITION
Authors: Foster Brian C. , Arnason J. Thor , Briggs Colin J.
Published: November 2004

▪ Abstract  Botanicals such as herbal products (HPs) and nutraceuticals (NCs) are often regarded as low risk because of their long history of human use. Anecdotal and literature reports of adverse drug events (ADEs) and clinical studies with HPs are increasing, but many of the reports are incomplete and contradictory. These reports need to identify confounding factors and explain contradictory findings if they are to help health care professionals or patients understand what risks are involved. HPs are complex botanicals, not single-active ingredient (SAI) products. Studies can be confounded by different manufacturing processes and formulations, including cosmetics and food supplements; environment; chemotypes; misidentification or adulteration; and factors associated with the patient or user population such as use, total drug load, and genetics. Future studies need to be conducted with characterized product that includes all commercially available related products. Clinical trials should be relevant to the user population and take into account the confounding factors that may influence the interpretation of the findings.
CALCIUM-ACTIVATED CHLORIDE CHANNELS
Authors: Hartzell Criss , Putzier Ilva , Arreola Jorge
Published: November 2004

▪ Abstract  Calcium-activated chloride channels (CaCCs) play important roles in cellular physiology, including epithelial secretion of electrolytes and water, sensory transduction, regulation of neuronal and cardiac excitability, and regulation of vascular tone. This review discusses the physiological roles of these channels, their mechanisms of regulation and activation, and the mechanisms of anion selectivity and conduction. Despite the fact that CaCCs are so broadly expressed in cells and play such important functions, understanding these channels has been limited by the absence of specific blockers and the fact that the molecular identities of CaCCs remains in question. Recent status of the pharmacology and molecular identification of CaCCs is evaluated.
UNLOCKING THE SECRETS OF CELL SIGNALING
Authors: Berridge Michael J.
Published: November 2004

▪ Abstract  My scientific life has been spent trying to understand how cells communicate with each other. This interest in cell signaling began with studies on the control of fluid secretion by an insect salivary gland, and the subsequent quest led to the discovery of inositol trisphosphate (IP3) and its role in calcium signaling, which effectively divided my scientific career into two distinct parts. The first part was primarily experimental and culminated in the discovery of IP3, which set the agenda for the second half during which I have enjoyed exploring the many functions of this remarkably versatile signaling system. It has been particularly exciting to find out how this IP3/Ca2+ signaling pathway has been adapted to control processes as diverse as fertilization, proliferation, cell contraction, secretion, and information processing in neuronal cells.
EXOCYTOSIS OF LUNG SURFACTANT: From the Secretory Vesicle to the Air-Liquid Interface
Authors: Dietl Paul , Haller Thomas
Published: November 2004

▪ Abstract  Exocytosis is fundamental in biology and requires an orchestra of proteins and other constituents to fuse a vesicle with the plasma membrane. Although the molecular fusion machinery appears to be well conserved in evolution, the process itself varies considerably with regard to the diversity of physico-chemical and structural factors that govern the delay between stimulus and fusion, the expansion of the fusion pore, the release of vesicle content, and, finally, its extracellular dispersion. Exocytosis of surfactant is unique in many of these aspects. This review deals with the secretory pathway of pulmonary surfactant from the type II cell to the air-liquid interface, with focus on the distinct mechanisms and regulation of lamellar body (LB) fusion and release. We also discuss the fate of secreted material until it is rearranged into units that finally function to reduce the surface tension in the lung.
MOLECULAR AND EVOLUTIONARY BASIS OF THE CELLULAR STRESS RESPONSE
Authors: Kültz Dietmar
Published: November 2004

▪ Abstract  The cellular stress response is a universal mechanism of extraordinary physiological/pathophysiological significance. It represents a defense reaction of cells to damage that environmental forces inflict on macromolecules. Many aspects of the cellular stress response are not stressor specific because cells monitor stress based on macromolecular damage without regard to the type of stress that causes such damage. Cellular mechanisms activated by DNA damage and protein damage are interconnected and share common elements. Other cellular responses directed at re-establishing homeostasis are stressor specific and often activated in parallel to the cellular stress response. All organisms have stress proteins, and universally conserved stress proteins can be regarded as the minimal stress proteome. Functional analysis of the minimal stress proteome yields information about key aspects of the cellular stress response, including physiological mechanisms of sensing membrane lipid, protein, and DNA damage; redox sensing and regulation; cell cycle control; macromolecular stabilization/repair; and control of energy metabolism. In addition, cells can quantify stress and activate a death program (apoptosis) when tolerance limits are exceeded.
CALCIUM, THIN FILAMENTS, AND THE INTEGRATIVE BIOLOGY OF CARDIAC CONTRACTILITY
Authors: Kobayashi Tomoyoshi , Solaro R. John
Published: November 2004

▪ Abstract  Although well known as the location of the mechanism by which the cardiac sarcomere is activated by Ca2+ to generate force and shortening, the thin filament is now also recognized as a vital component determining the dynamics of contraction and relaxation. Molecular signaling in the thin filament involves steric, allosteric, and cooperative mechanisms that are modified by protein phosphorylation, sarcomere length and load, the chemical environment, and isoform composition. Approaches employing transgenesis and mutagenesis now permit investigation of these processes at the level of the systems biology of the heart. These studies reveal that the thin filaments are not merely slaves to the levels of Ca2+ determined by membrane channels, transporters and exchangers, but are actively involved in beat to beat control of cardiac function by neural and hormonal factors and by the Frank-Starling mechanism.
REGULATION OF SIGNAL TRANSDUCTION PATHWAYS BY ESTROGEN AND PROGESTERONE
Authors: Edwards Dean P.
Published: November 2004

▪ Abstract  The female sex steroid hormones 17β-estradiol and progesterone mediate their biological effects on development, differentiation, and maintenance of reproductive tract and other target tissues through gene regulation by nuclear steroid receptors that function as ligand-dependent transcription factors. However, not all effects of 17β-estradiol and progesterone are mediated by direct control of gene expression. These hormones also have rapid stimulatory effects on the activities of a variety of signal transduction molecules and pathways and, in many cases, these effects appear to be initiated from the plasma cell membrane. There is growing evidence that a subpopulation of the conventional nuclear steroid receptor localized at the cell membrane mediates many of the rapid signaling actions of steroid hormones; however, novel membrane receptors unrelated to conventional steroid receptors have also been implicated. This chapter reviews the nature of the receptors that mediate rapid signaling actions of estrogen and progesterone and describes the signaling molecules and pathways involved, the mechanisms by which receptors couple with components of signaling complexes and trigger responses, and the target tissues and cell functions regulated by this mode of steroid hormone action.
MAKING SENSE OF RELIGION IN POLITICAL LIFE
Authors: Wald Kenneth D. , Silverman Adam L. , Fridy Kevin S.
Published: November 2004

▪ Abstract  After a long period of postwar neglect by mainstream scholars, religion assumed a new prominence in political science during the late 1970s. Despite the latter-day significance accorded religion by the discipline, the product of several unexpected real-world events, much of the recent research has focused on specific episodes or groups without drawing on or developing general theories. Social movement theory (SMT), particularly in its most recent incarnation, offers a way to address the three critical questions about religiously engaged political movements: What are the motives for political activity by religious groups? By what means do these groups facilitate political action? What features and conditions of the political system provide them opportunities for effective political action? This review explores various expressions of religiously based political action from the vantage point of SMT. We conclude that the translation of religious grievances into political action is contingent on a string of conditions that involve the interplay of motive, means, and opportunity. The implicit message is that scholars should approach religiously engaged social movements with the same theoretical frameworks used to understand secular political forces and that focusing these interpretive lenses on religion will illuminate issues of general interest to the discipline.
Indeterminacy in Brain and Behavior
Authors: Glimcher Paul W.
Published: November 2004

The central goal of modern science that evolved during the Enlightenment was the empirical reduction of uncertainty by experimental inquiry. Although there have been challenges to this view in the physical sciences, where profoundly indeterminate events have been identified at the quantum level, the presumption that physical phenomena are fundamentally determinate seems to have defined modern behavioral science. Programs like those of the classical behaviorists, for example, were explicitly anchored to a fully deterministic worldview, and this anchoring clearly influenced the experiments that those scientists chose to perform. Recent advances in the psychological, social, and neural sciences, however, have caused a number of scholars to begin to question the assumption that all of behavior can be regarded as fundamentally deterministic in character. Although it is not yet clear whether the generative mechanisms for human and animal behavior will require a philosophically indeterminate approach, it is clear that behavioral scientists of all kinds are beginning to engage the issues of indeterminacy that plagued physics at the beginning of the twentieth century.