Demonstrating

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Demonstrating

  • data demonstrating
  • evidence demonstrating
  • first report demonstrating
  • report demonstrating
  • studies demonstrating


  • Selected Abstracts


    Magnetic and Electrochemical Properties of a Heterobridged ,-Phenoxido,,1,1 -Azide Dinickel(II) Compound: A Unique Example Demonstrating the Bridge Distance Dependency of Exchange Integral

    EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 33 2009
    Rajesh Koner
    Abstract The synthesis, structure, magnetic and electrochemical properties of the heterobridged ,-phenoxido,,1,1 -azide dinickel(II) compound [NiII2(HL1)3(,1,1 -N3)]·3H2O (1) derived from the tetradentate Schiff base ligand N -(2-hydroxyethyl)-3-methoxysalicylaldimine (H2L1) are described. The title compound crystallizes in the triclinic system (space group P). Electrochemical analyses reveal that compound 1 exhibits two-step quasireversible couples in the reduction window with E1/2 values of ,1412 and ,1762 mV. The variable-temperature (2,300 K) magnetic susceptibilities at 1 T of the title compound were measured. The interaction between the metal centres is weak ferromagnetic (J = 5.0 cm,1, g = 2.23, D1 = 29.2 cm,1 and D2 = 10.7 cm,1). Comparison of the exchange integral of 1 with that of the only reported ,-phenoxido,,1,1 -azide dinickel(II) compound results in the emergence of a unique example of the dependence of strength of magnetic exchange interaction on the metal,ligand bridge distance. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]


    An Empirical Investigation Demonstrating the Multidimensional DIF Paradigm: A Cognitive Explanation for DIF

    JOURNAL OF EDUCATIONAL MEASUREMENT, Issue 2 2001
    Cindy M. Walker
    Differential Item Functioning (DIF) is traditionally used to identify different item performance patterns between intact groups, most commonly involving race or sex comparisons. This study advocates expanding the utility of DIF as a step in construct validation. Rather than grouping examinees based on cultural differences, the reference and focal groups are chosen from two extremes along a distinct cognitive dimension that is hypothesized to supplement the dominant latent trait being measured. Specifically, this study investigates DIF between proficient and non-proficient fourth- and seventh-grade writers on open-ended mathematics test items that require students to communicate about mathematics. It is suggested that the occurrence of DIF in this situation actually enhances, rather than detracts from, the construct validity of the test because, according to the National Council of Teachers of Mathematics (NCTM), mathematical communication is an important component of mathematical ability, the dominant construct being assessed. However, the presence of DIF influences the validity of inferences that can be made from test scores and suggests that two scores should be reported, one for general mathematical ability and one for mathematical communication. The fact that currently only one test score is reported, a simple composite of scores on multiple-choice and open-ended items, may lead to incorrect decisions being made about examinees. [source]


    Ionic Liquids Made with Dimethyl Carbonate: Solvents as well as Boosted Basic Catalysts for the Michael Reaction

    CHEMISTRY - A EUROPEAN JOURNAL, Issue 45 2009
    Massimo Fabris Dr.
    Abstract This article describes 1),a methodology for the green synthesis of a class of methylammonium and methylphosphonium ionic liquids (ILs), 2),how to tune their acid,base properties by anion exchange, 3),complete neat-phase NMR spectroscopic characterisation of these materials and 4),their application as active organocatalysts for base-promoted carbon,carbon bond-forming reactions. Methylation of tertiary amines or phosphines with dimethyl carbonate leads to the formation of the halogen-free methyl-onium methyl carbonate salts, and these can be easily anion-exchanged to yield a range of derivatives with different melting points, solubility, acid,base properties, stability and viscosity. Treatment with water, in particular, yields bicarbonate-exchanged liquid onium salts. These proved strongly basic, enough to efficiently catalyse the Michael reaction; experiments suggest that in these systems the bicarbonate basicity is boosted by two orders of magnitude with respect to inorganic bicarbonate salts. These basic ionic liquids used in catalytic amounts are better even than traditional strong organic bases. The present work also introduces neat NMR spectroscopy of the ionic liquids as a probe for solute,solvent interactions as well as a tool for characterisation. Our studies show that high catalytic efficacy of functional ionic liquids can be achieved by integrating their green synthesis, along with a fine-tuning of their structure. Demonstrating that ionic liquid solvents can be made by a truly green procedure, and that their properties and reactivity can be tailored to the point of bridging the gap between their use as solvents and as catalysts. [source]


    Demonstrating the clinical and cost effectiveness of adhesion reduction strategies

    COLORECTAL DISEASE, Issue 5 2002
    M. S. Wilson
    Abstract Objective To examine the feasibility of conducting Randomized Controlled Trials (RCT) in lower abdominal surgery to demonstrate a reduction in adhesion-related admissions following use of an adhesion reduction product, and to model the cost effectiveness of such products. Methods The number of patients in each limb of a RCT comparing an adhesion reduction product to a control has been estimated based on 25% and 50% reductions in adhesion-related readmissions one year after surgery, for P = 0.05 at a power of 80% and P = 0.01 at a power of 90%. A cost effectiveness model based on the Surgical and Clinical Adhesions Research Group (SCAR) database has been developed which calculates the percentage reduction in readmissions required of an adhesion reduction product to return the cost of investment. It also estimates the cumulative costs of adhesion-related readmissions for lower abdominal surgery and the cost savings associated with an adhesion reduction policy using a low or high cost product. Results 7.2% of patients undergoing lower abdominal surgery will readmit due to adhesions in the first year after surgery. To demonstrate a 25% reduction in readmissions one year after surgery, it is calculated that a RCT would require between 5686 (P = 0.05, power = 80%) and 7766 (P = 0.01, power = 90%) lower abdominal surgery patients followed-up for one year. A cost effectiveness analysis demonstrates that routine use of adhesion reduction products costing £50 per patient will payback the cost of such investment if they reduce adhesion-related readmissions by 16% after 3 years. A product costing £200 will need to offer a 64.1% reduction in readmissions after 3 years. For the estimated 158 000 lower abdominal surgery operations conducted in the UK each year, the cumulative costs of adhesion-related readmissions over 10 years are estimated at £569 Million. Conclusion Demonstrating the clinical effectiveness of adhesion reduction products in the RCT setting is unlikely to be feasible due to the large number of patients required. Products costing £200 or more are unlikely to payback their direct costs. [source]


    PHYSICAL TRAINING, ETHICAL DISCIPLINE, AND CREATIVE VIOLENCE: Zones of Self-Mastery in the Hindu Nationalist Movement

    CULTURAL ANTHROPOLOGY, Issue 1 2010
    ARAFAAT A. VALIANI
    ABSTRACT This essay advances understanding of how projects of self-mastery within neighborhood physical training programs associated with the Hindu Nationalist Movement produce subjects that are simultaneously ethically oriented and creatively violent. Such an analysis is contrasted with the conventional view that Hindu Nationalist volunteers are mere objects who blindly conform to a nationalist ideology or religious norms. Drawing on the author's participant observation of physical conditioning within the movement, the essay illustrates how combat training depends on an analytical sensibility by which techniques of drill are simultaneously learned and innovated by volunteers in a disciplinary zone of self-experimentation. Within such a zone, volunteers modify drill routines, enriching and refining them on an everyday basis. Thus, the evolution of physical techniques transforms training into an unfolding enterprise that is continually oriented toward attaining physical and moral self-mastery through the probing of bodily exercises. The essay underscores the social significance of such forms of physical self-exploration, in which movement volunteers understand the iterative probing of physical practice as driven by a resolve that deepens the volunteer's moral fortitude. The essay illuminates how a set of physical and moral processes are intertwined, processes through which militant subjects are culturally formed and routines of violence are sustained as a social and ethical practice. Physical training is connected to anti-Muslim pogroms in postcolonial Gujarat demonstrating how the evolving nature of physical training shapes, prolongs, and enables the improvisation of tactics of ethnic cleansing. [source]


    Photoperiodic differences in a forebrain nucleus involved in vocal plasticity: Enkephalin immunoreactivity reveals volumetric variation in song nucleus lMAN but not NIf in male European starlings (Sturnus vulgaris)

    DEVELOPMENTAL NEUROBIOLOGY, Issue 11 2010
    Tyler J. Stevenson
    Abstract Seasonal variation in the volume of various song control nuclei in many passerine species remains one of the best examples of naturally occurring adult neuroplasticity among vertebrates. The lateral portion of the magnocellular nucleus of the anterior nidopallium (lMAN) is a song nucleus that is important for song learning and seems to be critical for inducing variability in the song structure that is later pruned via a feedback process to produce adult crystallized song. To date, lMAN has not been shown to exhibit seasonal changes in volume, probably because it is difficult to resolve the boundaries of lMAN when employing histological methods based on Nissl staining. Here, lMANcore volumes were examined in intact photostimulated (i.e., breeding), castrated photostimulated and photorefractory (i.e., nonbreeding) male starlings (Sturnus vulgaris) to investigate the degree of seasonal variation in brain morphology. We present data demonstrating that the volumes of the total MAN and lMANcore delineated by enkephalin immunoreactivity are greater in photostimulated male starlings as compared to photorefractory males. Moreover, two other regions associated with the song system that have not been investigated previously in the context of seasonal plasticity namely (i) the medial portion of MAN (mMAN), and (ii) the nucleus interfacialis (NIf) did not display significant volumetric variation. We propose that greater lMANcore volumes are associated with the increase in vocal plasticity that is generally observed prior to production of stereotyped song. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 751,763, 2010 [source]


    Oral antidiabetic agents as cardiovascular drugs

    DIABETES OBESITY & METABOLISM, Issue 1 2007
    D. P. Macfarlane
    The increased risk of cardiovascular disease associated with type 2 diabetes is well documented. Lesser degrees of abnormal glucose metabolism including impaired fasting glycaemia and impaired glucose tolerance are also associated with increased cardiovascular risk. Studies showing improved cardiovascular outcomes with oral antidiabetic agents are limited, with the UKPDS demonstrating improved macrovascular outcomes only in a subgroup of obese patients with type 2 diabetes treated with metformin, and the heavily criticized STOP NIDDM trial showing a reduction in the number of cardiovascular events with the alpha glucosidase inhibitor acarbose. In recent years there has been an increase in the number of oral antidiabetic drugs available to treat the hyperglycaemia of diabetes. Some of these drugs have complex metabolic properties, additional to their antihyperglycaemic effect, improving endothelial function and markers of atherogenesis, with the potential to reduce cardiovascular morbidity and mortality, as supported by the recently published results of the PROACTIVE study. The results of further long-term cardiovascular outcome studies with these newer agents are awaited. [source]


    A one-dimensional model for simulating armouring and erosion on hillslopes: 2.

    EARTH SURFACE PROCESSES AND LANDFORMS, Issue 10 2007
    Long term erosion, armouring predictions for two contrasting mine spoils
    Abstract This paper investigates the dynamics of soil armouring as a result of fluvial erosion for a non-cohesive sandy gravel spoil from the Ranger Mine, Australia, and a cohesive silt loam spoil from the Northparkes Mine, Australia, using a model for hillslope soil armouring. These long term predictions concentrate on the temporal and spatial changes of the spoil grading and erosion over 100,200 years for the flat cap regions (1,2%) and steep batter edges (10,30%) typically encountered on waste rock dumps. The existence of a significant rock fragment fraction in the Ranger spoil means that it armours readily, while Northparkes does not. For Ranger the waste rock showed reductions in (1) cumulative erosion of up to 81% from that obtained by extrapolating the initial erosion rate out 100 years and (2) the erosion/year by more than 10-fold. For Northparkes reductions were less marked, with the maximum reduction in erosion/year being 37% after 200 years. For Ranger the reductions were greatest and fastest for intermediate gradient hillslopes. For the steepest hillslopes the armouring decreased because the flow shear stresses were large enough to mobilize all material in the armour layer. Model uncertainty was assessed with probabilistic confidence limits demonstrating that these erodibility reductions were statistically significant. A commonly used hillslope erosion model (sediment flux = ,1 discharge m1 slope n1) was fitted to these predictions. The erodibility, ,1, and m1 decreased with time, which was consistent with our physical intuition about armouring. At Ranger the parameter m1 asymptoted to 1·5,1·6 while at Northparkes it asymptoted to 1·2,1·3. At Ranger transient spatial trends in armouring led to a short term (50,200 years in the future) reduction in n1, to below zero under certain circumstances, recovering to an asymptote of about 0·5,1. At Northparkes n1 asymptoted to about 0·6, with no negative transients predicted. The m1 and n1 parameters predicted for Ranger were shown to be consistent with field data from a 10-year-old armoured hillslope and consistent with published relationships between erodibility and rock content for natural hillslopes. Copyright © 2007 John Wiley & Sons, Ltd. [source]


    A general framework for neutral models of community dynamics

    ECOLOGY LETTERS, Issue 12 2009
    Omri Allouche
    Abstract Neutral models of community dynamics are a powerful tool for ecological research, but their applications are currently limited to unrealistically simple types of dynamics and ignore much of the complexity that characterize natural ecosystems. Here, we present a new analytical framework for neutral models that unifies existing models of neutral communities and extends the applicability of existing models to a much wider spectrum of ecological phenomena. The new framework extends the concept of neutrality to fitness equivalence and in spite of its simplicity explains a wide spectrum of empirical patterns of species diversity including positive, negative and unimodal productivity,diversity relationships; gradual and highly delayed declines in species diversity with habitat loss; and positive and negative responses of species diversity to habitat heterogeneity. Surprisingly, the abundance distribution in all of these cases is given by the dispersal limited multinomial (DLM), the abundance distribution in Hubbell's zero-sum model, showing DLM's robustness and demonstrating that it cannot be used to infer the underlying community dynamics. These results support the hypothesis that ecological communities are regulated by a limited set of fundamental mechanisms much simpler than could be expected from their immense complexity. Ecology Letters (2009) 12: 1287,1297 [source]


    Tributaries influence recruitment of fish in large rivers

    ECOLOGY OF FRESHWATER FISH, Issue 4 2009
    B. M. Pracheil
    Abstract,,, Recent work demonstrates that tributary inputs are important community reorganisation points for river biota; however, no studies have examined the long-term effects of tributary inputs on fish population dynamics. This study examines nearly 40 years of young-of-year (yoy) paddlefish recruitment data to investigate the hypothesis that tributaries influence mainstem fish population dynamics. We generated hydrological variables from daily mean flow data (1965,2007) from an impounded reach of the mainstem Missouri River and from the Niobrara River, a relatively unaltered tributary, using Indicators of Hydrologic Alteration software. Three multiple regression models using natural-log transformed catch per unit effort (log cpue) as the response variable were created using (1) Missouri River-only flow variables, (2) Niobrara River-only flow variables and (3) Missouri River and Niobrara River flow variables. Flow variables from the Niobrara River explain a greater proportion of yoy paddlefish log cpue variability demonstrating that tributaries can positively impact fish population dynamics in altered rivers. [source]


    Women's Early Modern Medical Almanacs in Historical Context

    ENGLISH LITERARY RENAISSANCE, Issue 3 2003
    A. S. Weber
    This article examines the prophetical and medical almanacs of two female authors of seventeenth century England, Sarah Jinner of London and Mary Holden of Sudbury. Their works do not resemble the writings of the ecstatic women prophets of the period, but should be contextualized within the increased interest in astrological prediction after mid-century, the increase in women's literacy, and the relaxation of censorship. The medical content of both almanac makers demonstrates a desire to preserve and transmit classically-based medical cures for women, and in the case of Jinner, possibly to inform women about abortefacient and emmenagogic drugs. Jinner's medicines are based on classical pharmacology, thus demonstrating that women's medicine of the period was not necessarily a distinct praxis from the Galenic and Hippocratic therapeutics of male university-trained physicians. [source]


    Individual Male Calling Pattern and Male Mating Success in the European Treefrog (Hyla arborea): Is there Evidence for Directional or Stabilizing Selection on Male Calling Behaviour?

    ETHOLOGY, Issue 2 2006
    Thomas W.P. Friedl
    In anurans, call properties are commonly classified based on within-male variability as being either static or dynamic. Numerous playback experiments in the laboratory have indicated that female preferences based on dynamic call properties are usually strongly directional, while female preferences based on static call properties are often stabilizing or weakly directional. However, there are only few studies demonstrating that female preferences for high values of dynamic call properties indeed exert directional selection on male calling behaviour in natural populations. Moreover, field studies investigating whether female preferences for values of static call properties around the mean of the population lead to currently operating stabilizing selection on male calling patterns in natural populations are completely lacking. Here I investigate for two consecutive breeding seasons male calling patterns and male mating success in a population of individually marked European treefrogs (Hyla arborea), a hylid frog with prolonged breeding season and a lek mating system. Individual male calling pattern as analysed in terms of seven temporal and spectral call properties did not differ between males that survived from one breeding season to the next and those not surviving. None of the seven call properties investigated differed significantly between mated and unmated males, indicating that there is no strong directional selection on male calling behaviour in the study population. However, in one study season males that produced calls with a number of pulses around the mean of the population were significantly more likely to obtain matings than males that produced calls with a number of pulses at the low or high end of the distribution. Thus, this study provides preliminary evidence for the operation of stabilizing selection on a static call property (i.e. the number of pulses per call) in a natural population of an anuran amphibian. [source]


    ,Communities of concern' in the family-based treatment of anorexia nervosa: towards a consensus in the Maudsley model

    EUROPEAN EATING DISORDERS REVIEW, Issue 6 2005
    Paul Rhodes
    Abstract The Maudsley model of family-based treatment for anorexia nervosa, first developed in the mid-1980s, has been the subject of a number of randomized controlled trials over the past 20 years, each demonstrating its efficacy. In the past 5 years, the model has developed into two streams with the emergence of a multiple family therapy format in the United Kingdom and Europe and the consolidation of single family practice in the United States, including the publication of a treatment manual. While the benefits of multiple family therapy have not yet been experimentally demonstrated, its potential lies in the solidarity that can be promoted between families in their fight against the anorexia. In this paper, we will argue that the standard manualized version of the Maudsley model might also be augmented to incorporate strategies that introduce a role for a wider community, specifically by employing practices derived from a model of generic family therapy called narrative therapy. Copyright © 2005 John Wiley & Sons, Ltd and Eating Disorders Association. [source]


    Tamm-Horsfall protein: a multilayered defence molecule against urinary tract infection

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2005
    M. D. Säemann
    Abstract Urinary tract infection (UTI) is the most common nonepidemic bacterial infection in humans, representing a constant danger for the host. Both innate and adaptive components of the immune system as well as stromal cells including bladder epithelium are involved in the prevention and clearance of UTI. However, the particular properties of the urogenital tract, which does not comprise typical physical barriers like a mucus or ciliated epithelium, necessitate soluble mediators with potent immunomodulatory capabilities. One candidate molecule capable of both mediating direct antimicrobial activity and alerting immune cells is the evolutionary conserved Tamm-Horsfall protein (THP). Tamm-Horsfall protein is exclusively produced by the kidney in the distal loop of Henle; however, its definite physiological function remains elusive. Mounting evidence indicates that beyond a mere direct antimicrobial activity, THP exerts potent immunoregulatory activity. Furthermore, the genetic ablation of the THP gene leads to severe infection and lethal pyelonephritis in an experimental model of UTI. Recent data are provided demonstrating that THP links the innate immune response with specific THP-directed cell-mediated immunity. In light of these novel findings we discuss the particular role of THP as a specialized defence molecule. We propose an integrated model of protective mechanisms against UTI where THP acts by two principle nonmutually exclusive mechanisms involving the capture of potentially dangerous microbes and the ability of this peculiar glycoprotein to induce robust protective immune responses against uropathogenic bacteria. [source]


    In vivo post-transcriptional regulation of CD154 in mouse CD4+ T cells

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2009
    Stefano Vavassori
    Abstract Interactions between CD40 and its ligand CD154 are involved in the progression of both cell mediated and innate immunity. These interactions are brought about by the transient expression of CD154 on activated CD4+ T cells, which is regulated, in part, at the level of mRNA turnover. Here we have focused on analyzing the pattern of post-transcriptional regulation in mouse CD4+ T cells in response to activation. Initial experiments identify a region of the murine CD154 mRNA that binds a polypyrimidine tract-binding protein-containing complex (mComplex I), which is activation-dependent and binds to a single CU-rich site within the 3, uTR Subsequent findings demonstrate that in vivo polyclonal activation of T cells leads to a pattern of differential CD154 mRNA stability that is directly dependent on extent of activation. Furthermore, in vitro activation of antigen-primed T cells shows that the CD154 mRNA half-life increases relative to that of unprimed cells. Importantly, this is the first report demonstrating that the regulation of CD154 in vivo is connected to an activation-induced program of mRNA decay and thus provides strong evidence for post-transcriptional mechanisms having a physiological role in regulating CD154 expression during an ongoing immune response. [source]


    IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2007
    Teresa Zelante
    Abstract Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases. We found here that the IL-23/IL-17 developmental pathway acted as a negative regulator of the Th1-mediated immune resistance to fungi and played an inflammatory role previously attributed to uncontrolled Th1 cell responses. Both inflammation and infection were exacerbated by a heightened Th17 response against Candida albicans and Aspergillus fumigatus, two major human fungal pathogens. IL-23 acted as a molecular connection between uncontrolled fungal growth and inflammation, being produced by dendritic cells in response to a high fungal burden and counter-regulating IL-12p70 production. Both IL-23 and IL-17 subverted the inflammatory program of neutrophils, which resulted in severe tissue inflammatory pathology associated with infection. Our data are the first demonstrating that the IL-23/IL-17 pathway promotes inflammation and susceptibility in an infectious disease model. As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi. See accompanying commentary: http://dx.doi.org/10.1002/eji.200737804 [source]


    Synthesis and Characterization of Radical Cations Derived from Mono- and Biferrocenyl-Substituted 2-Aza-1,3-butadienes: A Study of the Influence of an Asymmetric and Oxidizable Bridge on Intramolecular Electron Transfer

    EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 12 2005
    Vega Lloveras
    Abstract The synthesis and study of structural and electronic properties of mono-ferrocenyl ,-conjugated complexes 5a,d, whose electronic characteristics have been systematically varied by introducing an electron-donating or electron-withdrawing substituent either at the 1-position or at the 4-position of the 2-aza-1,3-butadiene moiety linked to the ferrocenyl unit, are presented. The structural and electronic properties of the homobimetallic complex 5f, with two ferrocene units linked through the asymmetric and oxidizable 2-aza-1,3-butadiene bridge, is also reported. The crystal structures of complexes 5b, 5d, and 5f show a large degree of conjugation in this family of compounds. Complexes 5 show a rich electrochemical behavior due both to the oxidation of ferrocenyl units and the 2-aza-1,3-butadiene bridge, as revealed by cyclic voltammetry. Radical cations 5+· were prepared from 5 by coulometric oxidations following their generation by absorption spectroscopy. The electronic properties of all reported neutral and oxidized ,-conjugated complexes have been investigated by means of UV/Vis,near-IR, EPR and 57Fe Mössbauer spectroscopy. The detailed study of mono-oxidized species 5a+·,5f+· has permitted the determination of the influence of an asymmetric bridge with an electroactive character on the intramolecular electron transfer (IET) phenomenon, thus demonstrating that the 2-aza-1,3-butadiene bridge promotes the IET between the two metallic units of 5f+· through two different pathways. The experimental data and conclusions are supported by DFT computations (B3LYP/3-21G*) and time-dependent DFT methods. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source]


    Requirement of cannabinoid CB1 receptors in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2010
    Chia-Shan Wu
    Abstract A role for endocannabinoid signaling in neuronal morphogenesis as the brain develops has recently been suggested. Here we used the developing somatosensory circuit as a model system to examine the role of endocannabinoid signaling in neural circuit formation. We first show that a deficiency in cannabinoid receptor type 1 (CB1R), but not G-protein-coupled receptor 55 (GPR55), leads to aberrant fasciculation and pathfinding in both corticothalamic and thalamocortical axons despite normal target recognition. Next, we localized CB1R expression to developing corticothalamic projections and found little if any expression in thalamocortical axons, using a newly established reporter mouse expressing GFP in thalamocortical projections. A similar thalamocortical projection phenotype was observed following removal of CB1R from cortical principal neurons, clearly demonstrating that CB1R in corticothalamic axons was required to instruct their complimentary connections, thalamocortical axons. When reciprocal thalamic and cortical connections meet, CB1R-containing corticothalamic axons are intimately associated with elongating thalamocortical projections containing DGL,, a 2-arachidonoyl glycerol (2-AG) synthesizing enzyme. Thus, 2-AG produced in thalamocortical axons and acting at CB1Rs on corticothalamic axons is likely to modulate axonal patterning. The presence of monoglyceride lipase, a 2-AG degrading enzyme, in both thalamocortical and corticothalamic tracts probably serves to restrict 2-AG availability. In summary, our study provides strong evidence that endocannabinoids are a modulator for the proposed ,handshake' interactions between corticothalamic and thalamocortical axons, especially for fasciculation. These findings are important in understanding the long-term consequences of alterations in CB1R activity during development, a potential etiology for the mental health disorders linked to prenatal cannabis use. [source]


    Single olfactory sensory neurons simultaneously integrate the components of an odour mixture

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2003
    Patricia Duchamp-Viret
    Abstract Most odours are complex mixtures. However, the capacities of olfactory sensory neurons (OSNs) to process complex odour stimuli have never been explored in air-breathing vertebrates. To face this issue, the present study compares the electrical responses of single OSNs to two odour molecules, delivered singly and mixed together, in rats in vivo. This work is the first aimed at demonstrating that single OSNs simultaneously integrate several chemical signals and which, furthermore, attempts to describe such processes for the whole concentration range over which single OSNs can work. The results stress that complex interactions occur between components in odour mixtures and that OSN responses to such mixtures are not simply predictable from the responses to their components. Three types of interactions are described. They are termed suppression, hypoadditivity and synergy, in accord with psychophysical terminology. This allows us to draw links between peripheral odour reception and central odour coding. Indeed, events occurring in single OSNs may account for the dominating or even the masking effects of odour molecules in complex mixtures, i.e. for the prevailing action of a minor component in the final qualitative perception of a mixture. We conclude that our observations with binary mixtures anticipate the complexity of processes which may rise at the level of a single OSN in physiological conditions. Following this hypothesis, a natural odour would induce a multi-chemical integration at the level of single OSNs which may result in refining their individual odour-coding properties, leading them to play a crucial role in the final performance of the olfactory system. [source]


    Therapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment (Adv. Eng.

    ADVANCED ENGINEERING MATERIALS, Issue 8 2009
    Mater.
    The cover shows life and dead assay demonstrating living cells within a cellulose sulfate capsule. More information can be found in the article by J. M. Lohr et al. on page B129. [source]


    SEXUAL DIMORPHISM AND ADAPTIVE SPECIATION: TWO SIDES OF THE SAME ECOLOGICAL COIN

    EVOLUTION, Issue 11 2003
    Daniel I. Bolnick
    Abstract Models of adaptive speciation are typically concerned with demonstrating that it is possible for ecologically driven disruptive selection to lead to the evolution of assortative mating and hence speciation. However, disruptive selection could also lead to other forms of evolutionary diversification, including ecological sexual dimorphisms. Using a model of frequency-dependent intraspecific competition, we show analytically that adaptive speciation and dimorphism require identical ecological conditions. Numerical simulations of individual-based models show that a single ecological model can produce either evolutionary outcome, depending on the genetic independence of male and female traits and the potential strength of assortative mating. Speciation is inhibited when the genetic basis of male and female ecological traits allows the sexes to diverge substantially. This is because sexual dimorphism, which can evolve quickly, can eliminate the frequency-dependent disruptive selection that would have provided the impetus for speciation. Conversely, populations with strong assortative mating based on ecological traits are less likely to evolve a sexual dimorphism because females cannot simultaneously prefer males more similar to themselves while still allowing the males to diverge. This conflict between speciation and dimorphism can be circumvented in two ways. First, we find a novel form of speciation via negative assortative mating, leading to two dimorphic daughter species. Second, if assortative mating is based on a neutral marker trait, trophic dimorphism and speciation by positive assortative mating can occur simultaneously. We conclude that while adaptive speciation and ecological sexual dimorphism may occur simultaneously, allowing for sexual dimorphism restricts the likelihood of adaptive speciation. Thus, it is important to recognize that disruptive selection due to frequency-dependent interactions can lead to more than one form of adaptive splitting. [source]


    Piezoelectric wafer active sensors for in situ ultrasonic-guided wave SHM

    FATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 8 2008
    L. YU
    ABSTRACT In situ structural health monitoring aims to perform on-demand interrogation of the structure to determine the presence of service-induced damage and defects using non-destructive evaluation ultrasonic wave methods. Recently emerged piezoelectric wafer active sensors (PWAS) have the potential to significantly improve damage detection and health monitoring. PWAS are low-profile transducers that can be permanently attached onto the structure or inserted in between composite laminates, and can perform structural damage detection in thin-wall structures using guided wave methods (Lamb, Rayleigh, SH, etc.). This paper describes the analytical and experimental work of using PWAS-guided waves for in situ structural damage detection on thin-wall structures. We begin with reviewing the guided wave theory in plate structures and PWAS principles. The mechanisms of Lamb wave excitation and detection using PWAS is presented. Subsequently, we address in turn the use of PWAS to generate Lamb waves for damage (cracks and corrosion) detection in metallic structures. Pulse-echo, pitch-catch, phased array and time reversal methods are illustrated demonstrating that PWAS Lamb-waves techniques are suitable for damage detection and structural health monitoring. The last part of the paper treats analytically and experimentally PWAS excitation and tuning in composite materials. The research results presented in this paper show that in situ SHM methodologies using PWAS transducers hold the promise for more efficient, effective and timely damage detection in thin-wall structures. [source]


    Pigment epithelium-derived factor binds to cell-surface F1 -ATP synthase

    FEBS JOURNAL, Issue 9 2010
    Luigi Notari
    Pigment epithelium-derived factor (PEDF), a potent blocker of angiogenesis in vivo, and of endothelial cell migration and tubule formation, binds with high affinity to an as yet unknown protein on the surfaces of endothelial cells. Given that protein fingerprinting suggested a match of a , 60 kDa PEDF-binding protein in bovine retina with Bos taurus F1 -ATP synthase ,-subunit, and that F1Fo -ATP synthase components have been identified recently as cell-surface receptors, we examined the direct binding of PEDF to F1. Size-exclusion ultrafiltration assays showed that recombinant human PEDF formed a complex with recombinant yeast F1. Real-time binding as determined by surface plasmon resonance demonstrated that yeast F1 interacted specifically and reversibly with human PEDF. Kinetic evaluations revealed high binding affinity for PEDF, in agreement with PEDF affinities for endothelial cell surfaces. PEDF blocked interactions between F1 and angiostatin, another antiangiogenic factor, suggesting overlapping PEDF-binding and angiostatin-binding sites on F1. Surfaces of endothelial cells exhibited affinity for PEDF-binding proteins of , 60 kDa. Antibodies to F1,-subunit specifically captured PEDF-binding components in endothelial plasma membranes. The extracellular ATP synthesis activity of endothelial cells was examined in the presence of PEDF. PEDF significantly reduced the amount of extracellular ATP produced by endothelial cells, in agreement with direct interactions between cell-surface ATP synthase and PEDF. In addition to demonstrating that PEDF binds to cell-surface F1, these results show that PEDF is a ligand for endothelial cell-surface F1Fo -ATP synthase. They suggest that PEDF-mediated inhibition of ATP synthase may form part of the biochemical mechanisms by which PEDF exerts its antiangiogenic activity. Structured digital abstract ,,MINT-7711286: angiostatin (uniprotkb:P00747) physically interacts (MI:0915) with F-ATPase alpha subunit (uniprotkb:P07251), F-ATPase beta subunit (uniprotkb:P00830), F-ATPase gamma subunit (uniprotkb:P38077), F-ATPase delta subunit (uniprotkb:Q12165) and F-ATPase epsilon subunit (uniprotkb:P21306) by competition binding (MI:0405) ,,MINT-7711113: angiostatin (uniprotkb:P00747) physically interacts (MI:0915) with F-ATPase epsilon subunit (uniprotkb:P21306), F-ATPase delta subunit (uniprotkb:Q12165), F-ATPase gamma subunit (uniprotkb:P38077), F-ATPase beta subunit(uniprotkb:P00830) and F-ATPase alpha subunit (uniprotkb:P07251) by surface plasmon resonance (MI:0107) ,,MINT-7711060: F-ATPase gamma subunit (uniprotkb:P38077), F-ATPase beta subunit (uniprotkb:P00830), F-ATPase alpha subunit (uniprotkb:P07251) and PEDF (uniprotkb:P36955) physically interact (MI:0915) by molecular sieving (MI:0071) ,,MINT-7711313: F-ATPase epsilon subunit (uniprotkb:P21306), F-ATPase delta subunit (uniprotkb:Q12165), PEDF (uniprotkb:P36955), F-ATPase alpha subunit (uniprotkb:P07251), F-ATPase beta subunit (uniprotkb:P00830) and F-ATPase gamma subunit(uniprotkb:P38077) physically interact (MI:0915) by molecular sieving (MI:0071) ,,MINT-7711083: PEDF (uniprotkb:P36955) physically interacts (MI:0915) with F-ATPase epsilon subunit (uniprotkb:P21306), F-ATPase delta subunit (uniprotkb:Q12165), F-ATPase gamma subunit (uniprotkb:P38077), F-ATPase beta subunit (uniprotkb:P00830) and F-ATPase alpha subunit (uniprotkb:P07251) by surface plasmon resonance (MI:0107) [source]


    Biochemical characteristics of C-terminal region of recombinant chitinase from Bacillus licheniformis, implication of necessity for enzyme properties

    FEBS JOURNAL, Issue 9 2008
    Hsu-Han Chuang
    The functional and structural significance of the C-terminal region of Bacillus licheniformis chitinase was explored using C-terminal truncation mutagenesis. Comparative studies between full-length and truncated mutant molecules included initial rate kinetics, fluorescence and CD spectrometric properties, substrate binding and hydrolysis abilities, thermostability, and thermodenaturation kinetics. Kinetic analyses revealed that the overall catalytic efficiency, kcat/Km, was slightly increased for the truncated enzymes toward the soluble 4-methylumbelliferyl- N-N,-diacetyl chitobiose or 4-methylumbelliferyl- N - N,- N,-triacetyl chitotriose or insoluble ,-chitin substrate. By contrast, changes to substrate affinity, Km, and turnover rate, kcat, varied considerably for both types of chitin substrates between the full-length and truncated enzymes. Both truncated enzymes exhibited significantly higher thermostabilities than the full-length enzyme. The truncated mutants retained similar substrate-binding specificities and abilities against the insoluble substrate but only had approximately 75% of the hydrolyzing efficiency of the full-length chitinase molecule. Fluorescence spectroscopy indicated that both C-terminal deletion mutants retained an active folding conformation similar to the full-length enzyme. However, a CD melting unfolding study was able to distinguish between the full-length and truncated mutant molecules by the two phases of apparent transition temperatures in the mutants. These results indicate that up to 145 amino acid residues, including the putative C-terminal chitin-binding region and the fibronectin (III) motif of B. licheniformis chitinase, could be removed without causing a seriously aberrant change in structure and a dramatic decrease in insoluble chitin hydrolysis. The results of the present study provide evidence demonstrating that the binding and hydrolyzing of insoluble chitin substrate for B. licheniformis chitinase was not dependent solely on the putative C-terminal chitin-binding region and the fibronectin (III) motif. [source]


    Potency and selectivity of inhibition of cathepsin K, L and S by their respective propeptides

    FEBS JOURNAL, Issue 20 2000
    Jocelyne Guay
    The prodomains of several cysteine proteases of the papain family have been shown to be potent inhibitors of their parent enzymes. An increased interest in cysteine proteases inhibitors has been generated with potential therapeutic targets such as cathepsin K for osteoporosis and cathepsin S for immune modulation. The propeptides of cathepsin S, L and K were expressed as glutathione S -transferase-fusion proteins in Escherichia coli. The proteins were purified on glutathione affinity columns and the glutathione S -transferase was removed by thrombin cleavage. All three propeptides were tested for inhibitor potency and found to be selective within the cathepsin L subfamily (cathepsins K, L and S) compared with cathepsin B or papain. Inhibition of cathepsin K by either procathepsin K, L or S was time-dependent and occurred by an apparent one-step mechanism. The cathepsin K propeptide had a Ki of 3.6,6.3 nm for each of the three cathepsins K, L and S. The cathepsin L propeptide was at least a 240-fold selective inhibitor of cathepsin K (Ki = 0.27 nm) and cathepsin L (Ki = 0.12 nm) compared with cathepsin S (Ki = 65 nm). Interestingly, the cathepsin S propeptide was more selective for inhibition of cathepsin L (Ki = 0.46 nm) than cathepsin S (Ki = 7.6 nm) itself or cathepsin K (Ki = 7.0 nm). This is in sharp contrast to previously published data demonstrating that the cathepsin S propeptide is equipotent for inhibition of human cathepsin S and rat and paramecium cathepsin L [Maubach, G., Schilling, K., Rommerskirch, W., Wenz, I., Schultz, J.E., Weber, E. & Wiederanders, B. (1997), Eur J. Biochem. 250, 745,750]. These results demonstrate that limited selectivity of inhibition can be measured for the procathepsins K, L and S vs. the parent enzymes, but selective inhibition vs. cathepsin B and papain was obtained. [source]


    Environmental issues related to end-of-life options of plastics containing brominated flame retardants

    FIRE AND MATERIALS, Issue 5 2004
    Lein Tange
    Abstract Bromine is used as the building block for some of the most effective flame retarding agents available to the plastics industry today. They are used to protect against the risk of accidental fires in a wide range of Electrical and Electronic Equipment (EEE). Brominated flame retardants (BFRs), as all flame retardants, act to decrease the risk of fire by increasing the fire resistance of the materials in which they are applied. There is a perception that BFRs affect adversely the end-of-life management of plastics through formation of Polybrominated Dibenzo Dioxins and Dibenzo Furans (PBDD/F). In fact, there exists a wide range of data and practical experience demonstrating that the end-of-life management of plastics containing BFRs is fully compliant with legislation setting the strictest limit values for PBDD/F and is fully compatible with an integrated waste management concept. Copyright © 2004 John Wiley & Sons, Ltd. [source]


    Effects of melatonin and caffeic acid phenethyl ester on testicular injury induced by myocardial ischemia/reperfusion in rats

    FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2005
    Mukaddes E
    Abstract Experimental studies indicate that ischemia/reperfusion (I/R) causes remote organ injury although the molecular mechanism has not been clearly defined. In this report, the role of oxidative injury on testicular damage following myocardial I/R injury and the effects of antioxidant agents, melatonin and caffeic acid phenethyl ester (CAPE), on testicular injury were investigated. As far as we know, this is the first report demonstrating that myocardial I/R induces damage to the testes. Thirty-two male Wistar rats were randomly divided into four groups: sham operation (SO), I/R + vehicle, I/R + melatonin, and I/R + caffeic acid phenethyl ester. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Serum nitric oxide (NO) and malondialdehyde (MDA) levels and morphological changes were examined. I/R was accompanied by a significant increase in serum MDA and NO levels, whereas, melatonin and CAPE administration significantly reduced these values. Melatonin was more efficient in reducing MDA levels than CAPE (P < 0.05). I/R induced myocardial damage, manifested as the histopathological evidence of intracellular vacuolization, interstitial edema, neutrophil infiltration and coagulative necrosis. I/R + vehicle group showed many histological alterations such as focal tubular atrophy, and degeneration and disorganization of the seminiferous epithelium in testes. The number of atrophic tubules and degenerating cells was significantly higher in I/R + vehicle group than that of SO group. Melatonin and CAPE significantly reduced the number of degenerating cells; additionally, melatonin reduced the number of atrophic tubules (P < 0.05). Our results indicate that myocardial I/R induces severe testicular damage and antioxidant agents, especially melatonin, have protective effects on testicular injury after myocardial I/R. Our data emphasize that oxygen-based reactants may play a central role in remote organ injury. [source]


    Multiple genomic alterations on 21q22 predict various TMPRSS2/ERG fusion transcripts in human prostate cancers

    GENES, CHROMOSOMES AND CANCER, Issue 11 2007
    Wennuan Liu
    A number of TMPRSS2/ERG fusion transcripts have been reported since the discovery that recurrent genomic rearrangements result in the fusion of TMPRSS2 and ETS family member genes. In this article we present evidence demonstrating that multiple genomic alterations contribute to the formation of various TMPRSS2/ERG transcripts. Using allele-specific analysis of the data generated from the GeneChip 500K SNP array we observed both hemizygous and homozygous deletions occurring at different locations between and within TMPRSS2 and ERG in prostate cancers. The 500K SNP array enabled us to fine map the start and end of each deletion to specific introns of these two genes, and to predict a variety of fusion transcripts, including a new form which was confirmed by sequence analysis of the fusion transcripts in various tumors. We also inferred that translocation is an additional mechanism of fusion for these two genes in some tumors, based on largely diploid genomic DNA between TMPRSS and ERG, and different fusion transcripts produced in these tumors. Using a bioinformatics approach, we then uncovered the consensus sequences in the regions harboring the breakpoints of the deletions. These consensus sequences were homologous to the human Alu-Sq and Alu-Sp subfamily consensus sequences, with more than 80% homology. The presence/absence of Alu family consensus sequence in the introns of TMPRSS2 and ERG correlates with the presence/absence of fusion transcripts of theses two genes, indicating that these consensus sequences may contribute to genomic deletions and the fusion of TMPRSS2 and ERG in prostate cancer. © 2007 Wiley-Liss, Inc. [source]


    The 3D shear experiment over the Natih field in Oman: the effect of fracture-filling fluids on shear propagation

    GEOPHYSICAL PROSPECTING, Issue 2 2001
    C.M. Van Der Kolk
    This is the final paper in a series on the 3D multicomponent seismic experiment in Oman. In this experiment a 3D data set was acquired using three-component geophones and with three source orientations. The data set will subsequently be referred to as the Natih 9C3D data set. We present, for the first time, evidence demonstrating that shear waves are sensitive to fluid type in fractured media. Two observations are examined from the Natih 9C3D data where regions of gas are characterized by slow shear-wave velocities. One is that the shear-wave splitting map of the Natih reservoir exhibits much larger splitting values over the gas cap on the reservoir. This increase in splitting results from a decrease in the slow shear-wave velocity which senses both the fractures and the fracture-filling fluid. Using a new effective-medium model, it was possible to generate a splitting map for the reservoir that is corrected for this fluid effect. Secondly, an anomaly was encountered on the shear-wave data directly above the reservoir. The thick Fiqa shale overburden exhibits a low shear-wave velocity anomaly that is accompanied by higher shear reflectivity and lower frequency content. No such effects are evident in the conventional P-wave data. This feature is interpreted as a gas chimney above the reservoir, a conclusion supported by both effective-medium modelling and the geology. With this new effective-medium model, we show that introduction of gas into vertically fractured rock appears to decrease the velocity of shear waves (S2), polarized perpendicular to the fracture orientation, whilst leaving the vertical compressional-wave velocity largely unaffected. This conclusion has direct implications for seismic methods in exploration, appraisal and development of fractured reservoirs and suggests that here we should be utilizing S-wave data, as well as the conventional P-wave data, as a direct hydrocarbon indicator. [source]


    The Archive and the Artist: The Stefan Heym Archive Revisited

    GERMAN LIFE AND LETTERS, Issue 1 2000
    K. E. Attar
    In December 1992 Cambridge University Library acquired the Stefan Heym Archive. This is a remarkably complete collection of literary manuscripts, interviews, letters, press clippings, audio and video tapes and miscellaneous material pertaining to a major literary and political figure in East German cultural history. The current article, using insights gained from cataloguing the archive, complements previous work demonstrating how the collection reflects the life of the originator and the historical events in which he participated. The article describes the various categories of manuscripts in the archive with an emphasis on what the collection reveals about Heym's work, his approach to it, and its reception. The literary manuscripts show the genesis of particular works, the timespan over which Heym's ideas develop, the method and care in their preparation, and Heym's greater interest in the creative process than in the end-product. Similar care is evident in the text of interviews. Media coverage, paper and taped material, shows the reception of Heym's work, includes Heym's comments on his own work, and demonstrates the growth of his status over the years. The archive's cultural value should not obscure its worth in shedding light on Heym as a writer. [source]