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Experimental Support (experimental + support)
Selected AbstractsIncreases in P-Wave Duration and Dispersion After Hemodialysis Are Totally (or Partially) Due to the Procedure-Induced Alleviation of the Body Fluid Overload: A Hypothesis with Strong Experimental SupportANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2005John E. Madias M.D. Increases in the P-wave duration (P-du) and P-wave dispersion (P-d) following hemodialysis (HD) are attributed to changes in the electrolytic milieu with HD, or are considered to be due to an unknown mechanism. Such changes are thought to be proarrhythmic, and thus have potential clinical implications. Increase in the amplitude of QRS complexes following HD has been amply documented in the literature. Also, recent work linking attenuation/augmentation of amplitude of QRS and P-wave complexes in patients with increase/subsequent decrease weights due to anasarca peripheral edema/and its alleviation, or before/after hemodialysis (HD) suggests that the increase in the P-du and P-d after HD may be totally (or partially) mediated by the alleviation of the fluid overload by the procedure. This is supported by the decrease/increase in the QRS duration noted with anasarca/and its alleviation. To further clarify this issue, and prove or refute the above hypothesis, it is recommended that correlations of changes in the P-du and P-d with the loss of weight or net fluid dialyzed are carried out, in addition to the traditional considerations of electrolytic alterations after HD. [source] Anion,, Slides for Transmembrane TransportCHEMISTRY - A EUROPEAN JOURNAL, Issue 1 2009Jiri Mareda Dr. Abstract The recognition and transport of anions is usually accomplished by hydrogen bonding, ion pairing, metal coordination, and anion,dipole interactions. Here, we elaborate on the concept to use anion,, interactions for this purpose. Different to the popular cation,, interactions, applications of the complementary ,-acidic surfaces do not exist. This is understandable because the inversion of the aromatic quadrupole moment to produce ,-acidity is a rare phenomenon. Here, we suggest that ,-acidic aromatics can be linked together to produce an unbendable scaffold with multiple binding sites for anions to move along across a lipid bilayer membrane. The alignment of multiple anion,, sites is needed to introduce a cooperative multi-ion hopping mechanism. Experimental support for the validity of the concept comes from preliminary results with oligonaphthalenediimide (O-NDI) rods. Predicted by strongly positive facial quadrupole moments, the cooperativity and chloride selectivity found for anion transport by O-NDI rods were consistent with the existence of anion,, slides. The proposed mechanism for anion transport is supported by DFT results for model systems, as well as MD simulations of rigid O-NDI rods. Applicability of anion,, slides to achieve electroneutral photosynthesis is elaborated with the readily colorizable oligoperylenediimide (O-PDI) rods. To clarify validity, scope and limitations of these concepts, a collaborative research effort will be needed to address by computer modeling and experimental observations the basic questions in simple model systems and to design advanced multifunctional anion,, architectures. [source] What Does the Conservation of Energy Have to Do with Physicalism?DIALECTICA, Issue 4 2006Barbara Montero The conservation of energy law, a law of physics that states that the total energy of any closed system is always conserved, is a bedrock principle that has achieved both broad theoretical and experimental support. Yet if interactive dualism is correct, it is thought that the mind can affect physical objects in violation of the conservation of energy. Thus, some claim, the conservation of energy grounds an argument for physicalism. Although critics of the argument focus on the implausibility of causation requiring the transference of energy, I argue that even if causation requires the transference of energy, once we accept the other required premises of the argument that lie behind any supposed argument from the conservation of energy the law of the conservation of energy is revealed as irrelevant to the question of whether the mental is physical. [source] A match,mismatch test of a stage model of behaviour change in tobacco smokingADDICTION, Issue 7 2006Arie Dijkstra ABSTRACT Aims An innovation offered by stage models of behaviour change is that of stage-matched interventions. Match,mismatch studies are the primary test of this idea but also the primary test of the validity of stage models. This study aimed at conducting such a test among tobacco smokers using the Social Cognitive Stage Model. Design A match,mismatch field-experiment was conducted in which smokers and ex-smokers in different stages were assigned randomly to one of three information conditions. Participants Smokers in the pre-contemplation stage, the contemplation stage and the preparation stage, and ex-smokers in the action stage (n = 481), who were recruited through mass media, were assigned randomly to one of three information conditions. Intervention In each of the three information conditions, participants received a four- to six-page computer-tailored letter designed to: (1) increase the positive outcome expectations of quitting, (2) decrease the negative outcome expectations of quitting or (3) increase self-efficacy. Measurements Forward stage transition was the primary outcome measure, which was assessed 2 months after the participants received the information. Findings At the 2-month follow-up, the matched interventions were significantly more effective in stimulating forward stage transition (44.7%) than were mismatched interventions (25.8%; odds ratio = 2.78; confidence interval = 1.85,4.35). Conclusion The present study provides experimental support for the benefits of stage-matching and for the validity of the Social Cognitive Stage Model. [source] Transcranial magnetic stimulation of the human frontal eye field facilitates visual awarenessEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003Marie-Hélène Grosbras Abstract What are the brain mechanisms allowing a stimulus to enter our awareness? Some theories suggest that this process engages resources overlapping with those required for action control, but experimental support for these ideas is still required. Here, we investigated whether the human frontal eye field (FEF), an area known to control eye movements, is involved in visual awareness. Volunteers participated in a backward masking task in which they were able to detect a target in a small proportion of trials. We observed that a single pulse of transcranial magnetic stimulation applied over the FEF shortly before the target's onset facilitated visual sensitivity; subjects were able to detect an otherwise subliminal object. These results show that modulating the neuronal activity of the FEF can enhance visual detection, thereby yielding new insights into the neural basis of visual awareness. [source] A NOVEL PREFERENCE FOR AN INVASIVE PLANT AS A MECHANISM FOR ANIMAL HYBRID SPECIATIONEVOLUTION, Issue 2 2007Dietmar Schwarz Homoploid hybrid speciation,speciation via hybridization without a change in chromosome number,is rarely documented and poorly understood in animals. In particular, the mechanisms by which animal homoploid hybrid species become ecologically and reproductively isolated from their parents are hypothetical and remain largely untested by experiments. For the many host-specific parasites that mate on their host, choosing the right host is the most important ecological and reproductive barrier between these species. One example of a host-specific parasite is the Lonicera fly, a population of tephritid fruit flies that evolved within the last 250 years likely by hybridization between two native Rhagoletis species following a host shift to invasive honeysuckle. We studied the host preference of the Lonicera fly and its putative parent species in laboratory experiments. The Lonicera fly prefers its new host, introduced honeysuckle, over the hosts of both parental species, demonstrating the rapid acquisition of preference for a new host as a means of behavioral isolation from the parent species. The parent taxa discriminate against each other's native hosts, but both accept honeysuckle fruit, leaving the potential for asymmetric gene flow from the parent species. Importantly, this pattern allows us to formulate hypotheses about the initial formation of the Lonicera fly. As mating partners from the two parent taxa are more likely to meet on invasive honeysuckle than on their respective native hosts, independent acceptance of honeysuckle by both parents likely preceded hybridization. We propose that invasive honeysuckle served as a catalyst for the local breakdown of reproductive isolation between the native parent species, a novel consequence of the introduction of an exotic weed. We describe behavioral mechanisms that explain the initial hybridization and subsequent reproductive isolation of the hybrid Lonicera fly. These results provide experimental support for a combination of host shift and hybridization as a model for hybrid speciation in parasitic animals. [source] A Measure of Representativeness of a Sample for Inferential PurposesINTERNATIONAL STATISTICAL REVIEW, Issue 2 2006Salvatore Bertino Summary After defining the concept of representativeness of a random sample, the author proposes a measure of how much the observed sample represents its parent distribution. This measure is called Representativeness Index. The same measure, seen as a function of a sample and of a distribution, will be called Representativeness Function. For a given sample it provides the value of the index for the different distributions under examination, and for a given distribution it provides a measure of the representativeness of its possible samples. Such Representativeness Function can be used in an inferential framework just as the likelihood function, since it gives to any distribution the "experimental support" provided by the observed sample. This measure is distribution-free and it is shown to be a transformation of the wellknown Cramér,von Mises statistic. By using the properties of that statistic, criteria for providing set estimators and tests of hypotheses are introduced. The utilization of the representativeness function in many standard statistical problems is outlined through examples. The quality of the inferential decisions can be assessed with the usual techniques (MSE, power function, coverage probabilities). The most interesting examples turn out to be those of situations that are "non-regular", as for instance the estimation of parameters involved in the support of the parent distribution, or less explored (model choice). Résumé Après avoir défini le concept de répresentativité d'un échantillon aléatoire, l'auteur propose une mesure de combien l'échantillon observé réprésente la distribution parente. Cette mesure est dite Fonction de Répresentativité. Pour un échantillon donné la fonction donne les valeurs de l'indice pour toutes le distributions de la famille consideée, tandis que, pour une distribution donnée, elle donne la mesure de la répresentativité de chaque possible échantillon. La Fonction de Répresentativité peut être employée dans les problèmes d'inference statistique justement comme la fonction de vraisemblance, puisque elle donne à chaque distribution le "support expérimental" produit par l'échantillon observé. La measure est à distribution libre et on demontre que elle est une tranformation de la bien connue statistique de Cramér,von Mises. En utilisant le propriétés de la dite statistique, on introduit des crières pour obtenir estimateur ensemblistes et test d'hypothèse. L'utilization de la fonction de répresentativité dans plusieurs problèmes statistique est montrée par des examples. La qualité des decisions inférentielles peut être evaluée par les techniques usuelles (MSE, fonction de puissance, probabiliés de couverture). Les examples les plus interessant sont ceux qui concerne les situations "non regulères", par exemple l'estimation de paramètres qui figurent dans le support de la population parente, ou situations moins exploées (choix du modèle). [source] Removing bias from solvent atoms in electron density mapsJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 4 2008Eric N. Brown Atomic structures of proteins determined via protein crystallography contain numerous solvent atoms. The experimental data for the determination of a water molecule's O-atom position is often a small contained blob of unidentified electron density. Unfortunately, the nature of crystallographic refinement lets poorly placed solvent atoms bias the future refined positions of all atoms in the crystal structure. This research article presents the technique of omit-maps applied to remove the bias introduced by poorly determined solvent atoms, enabling the identification of incorrectly placed water molecules in partially refined crystal structures. A total of 160 protein crystal structures with 45,912 distinct water molecules were processed using this technique. Most of the water molecules in the deposited structures were well justified. However, a few of the solvent atoms in this test data set changed appreciably in position, displacement parameter or electron density when fitted to the solvent omit-map, raising questions about how much experimental support exists for these solvent atoms. [source] NF- ,B in liver diseases: a target for drug therapyJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2009Pablo Muriel Abstract There are five nuclear factor- ,B (NF- ,B) transcription factors with important roles in innate immunity, liver inflammation, fibrosis and apoptosis prevention. Several inhibitors of NF- ,B, like caffeic acid, captopril, curcumin, pyrrolidine dithiocarbamate, resveratrol, silymarin and thalidomide, have demonstrated antinecrotic, anticholestatic, antifibrotic and anticancer activities in the liver. A link between inflammation and hepatocellular carcinoma through the NF- ,B pathway has been observed, providing ample experimental support for the tumor-promoting function of NF- ,B in various models of cancer. NF- ,B has been associated with the induction of proinflammatory gene expression and has attracted interest as a target for the treatment of inflammatory disease. However, despite much attention being focused on the deleterious effects of NF- ,B, activation of this factor during the resolution of inflammation is associated with the production of antiinflammatory molecules like interleukin (IL)-10 and the onset of apoptosis. This suggests that NF- ,B has an antiinflammatory role in vivo involving the regulation of the resolution of inflammation. Also, NF- ,B promotes liver regeneration by upregulating IL-6 and other molecules like hepatocyte growth factor. It has been postulated that the beneficial properties of NF- ,B are due to p50 homodimers, whose activation prevents cholestatic and chronic liver injury. More basic understanding on the function of the diverse NF- ,B factors is urgently needed in different physiological and pathological conditions, because depending on the subunit composition of the dimmer, the disease and the stage of the illness, inhibition of the factor may result in a beneficial or in a deleterious response. Copyright © 2008 John Wiley & Sons, Ltd. [source] Supporting scientific discovery learning in a simulation environmentJOURNAL OF COMPUTER ASSISTED LEARNING, Issue 1 2003D.J. Reid Abstract Until recent times, most studies on supporting simulation-based scientific discovery learning adopted the ad hoc strategies-oriented approach. This paper makes a systematic analysis of the internal conditions of scientific discovery learning to propose a triple scheme for learning support design that includes interpretative support (IS), experimental support (ES), and reflective support (RS). The experiment was conducted with 78 students (aged from 12 to 13 years) to examine the effects of the IS and ES using a 2x2 between-subjects design. The main results were: significant effects were observed for IS on the post-test of intuitive understanding, flexible application and knowledge integration; no main effect was demonstrated for ES, and there was a marginally significant interactive effect for ES and IS on the intuitive understanding test. A process analysis showed that the successful learners had designed more well-controlled experiments than the failing ones. Learning support in a simulation environment should be directed toward the three perspectives to invite meaningful, systematic and reflective discovery learning. [source] Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequencesLIVER INTERNATIONAL, Issue 4 2001Dimitrios-Petrou Bogdanos Abstract: The pathogenesis of autoimmune liver disease and autoimmunity associated with chronic viral hepatitis remains poorly understood. One of the major hurdles to a deeper understanding of these pathological processes is the absence of clearly defined inductive mechanisms, which, if identified and characterised, could guide clinical strategies for their prevention or allow therapeutic intervention. Molecular mimicry leading to crossreactive autoimmune responses has gained strong experimental support in the past decade. A fundamental premise of this hypothesis is the involvement of a mimicking environmental trigger. In view of the numerous viral and bacterial agents epidemiologically linked to autoimmune liver diseases, we and others have proposed molecular mimicry to be an important mechanism in these diseases. We also propose similar crossreactive mechanisms to operate in the generation of autoimmunity in viral hepatitis. This review focuses on molecular mimicry at the level of the B-cell, as few data on T-cell crossreactivity in liver disease are thus far available. [source] Chemotopic odorant coding in a mammalian olfactory system,THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2007Brett A. Johnson Abstract Systematic mapping studies involving 365 odorant chemicals have shown that glomerular responses in the rat olfactory bulb are organized spatially in patterns that are related to the chemistry of the odorant stimuli. This organization involves the spatial clustering of principal responses to numerous odorants that share key aspects of chemistry such as functional groups, hydrocarbon structural elements, and/or overall molecular properties related to water solubility. In several of the clusters, responses shift progressively in position according to odorant carbon chain length. These response domains appear to be constructed from orderly projections of sensory neurons in the olfactory epithelium and may also involve chromatography across the nasal mucosa. The spatial clustering of glomerular responses may serve to "tune" the principal responses of bulbar projection neurons by way of inhibitory interneuronal networks, allowing the projection neurons to respond to a narrower range of stimuli than their associated sensory neurons. When glomerular activity patterns are viewed relative to the overall level of glomerular activation, the patterns accurately predict the perception of odor quality, thereby supporting the notion that spatial patterns of activity are the key factors underlying that aspect of the olfactory code. A critical analysis suggests that alternative coding mechanisms for odor quality, such as those based on temporal patterns of responses, enjoy little experimental support. J. Comp. Neurol. 503:1,34, 2007. © 2007 Wiley-Liss, Inc. [source] Auxin-induced, SCFTIR1 -mediated poly-ubiquitination marks AUX/IAA proteins for degradationTHE PLANT JOURNAL, Issue 1 2009Felipe Dos Santos Maraschin Summary The plant hormone auxin (indole-3-acetic acid or IAA) regulates plant development by inducing rapid cellular responses and changes in gene expression. Auxin promotes the degradation of Aux/IAA transcriptional repressors, thereby allowing auxin response factors (ARFs) to activate the transcription of auxin-responsive genes. Auxin enhances the binding of Aux/IAA proteins to the receptor TIR1, which is an F-box protein that is part of the E3 ubiquitin ligase complex SCFTIR1. Binding of Aux/IAA proteins leads to degradation via the 26S proteasome, but evidence for SCFTIR1 -mediated poly-ubiquitination of Aux/IAA proteins is lacking. Here we used an Arabidopsis cell suspension-based protoplast system to find evidence for SCFTIR1 -mediated ubiquitination of the Aux/IAA proteins SHY2/IAA3 and BDL/IAA12. Each of these proteins showed a distinct abundance and repressor activity when expressed in this cell system. Moreover, the amount of endogenous TIR1 protein appeared to be rate-limiting for a proper auxin response measured by the co-transfected DR5::GUS reporter construct. Co-transfection with 35S::TIR1 led to auxin-dependent degradation, and excess of 35S::TIR1 even led to degradation of Aux/IAAs in the absence of auxin treatment. Expression of the mutant tir1-1 protein or the related F-box protein COI1, which is involved in jasmonate signaling, had no effect on Aux/IAA degradation. Our results show that SHY2/IAA3 and BDL/IAA12 are poly-ubiquitinated and degraded in response to increased auxin or TIR1 levels. In conclusion, our data provide experimental support for the model that SCFTIR1 -dependent poly-ubiquitination of Aux/IAA proteins marks these proteins for degradation by the 26S proteasome, leading to activation of auxin-responsive gene expression. [source] Declining and low fecal corticoids are associated with distress, not acclimation to stress, during the translocation of African rhinocerosANIMAL CONSERVATION, Issue 1 2010W. L. Linklater Abstract Concentrations of adrenal steroid metabolites in feces are routinely used to assess the welfare of animals that are the subject of conservation efforts. The assumption that low and declining corticoid concentrations indicate the absence of stress and acclimation, respectively, is often made without experimental support or wild-animal comparisons, although intrinsic control of adrenal steroids might occur even under ongoing stress and distress. We adopted the capture and 11-week captivity of 18 black (Diceros bicornis: 11 males, seven females) and 52 white (Ceratotherium simum: 22 males, 30 females) rhinoceros as an experimental test of the relationship between corticoid concentrations and stress (translocation) and measured for suppressed gonad function as an indicator of distress , the biological cost of cumulative stressors. Fecal samples collected from the rectum at capture and during captivity were stored frozen and their corticoid, and androgen (in males) or progestin (in females), concentrations determined by radioimmunoassay. Corticoid profiles followed the expected pattern of being two to five times pre-capture levels (ng g,1: black rhino: female 24.5±3.7, male 23.9±2.2; white rhino: female 16.3±1.6, male 12.3±2.4) for up to 17 days after capture and declined with time in captivity. Black rhinoceros and male white rhinoceros corticoids declined below pre-capture values and were associated with suppressed levels of androgens and progestins with increased time in captivity. Declining corticoids could not be interpreted as acclimation or the absence of stressors, without also measuring for distress in African rhinoceros. White rhinoceros female corticoid values remained elevated, although their gonad steroid levels were also suppressed. We discuss our findings for the management of rhinoceros in the wild and captivity. [source] 5-HT1B but not 5-HT6 or 5-HT7 receptors mediate depression of spinal nociceptive reflexes in vitroBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2002G Hedo The identity of the serotonin (5-HT) receptors modulating the transmission of segmental C-fibre mediated signals was studied using an in vitro preparation of the hemisected spinal cord from rat pups. Responses to trains of stimuli delivered to a lumbar dorsal root were recorded from the corresponding ventral root. The resulting cumulative depolarization (CD) mediated by unmyelinated fibres was quantified in terms of integrated area. The amplitude of the mono-synaptic reflex was also measured. Serotonergic agents were superfused at known concentrations and their effects on the reflexes evaluated. 5-HT had depressant effects on the CD (EC50 34 ,M). The rank order of potency of agonists for the depression of the CD was 5-carboxamidotryptamine (5-CT)>,-methylserotonin (,-met-5-HT) ,5-HT>42-methylserotonin (2-met-5-HT),8-OH-DPAT. All the agonists including 2-met-5-HT and 8-OH-DPAT had strong depressant effects on the mono-synaptic reflex with the following order of potency: 5-CT>48-OH-DPAT>4,-met-5-HT ,5-HT,2-met-5-HT. The inhibitory effects of 5-HT, ,-met-5-HT and 5-CT were attenuated by the non-specific 5-HT antagonist methiothepin (1 ,M) and by the 5-HT1A/1B antagonist SDZ 21009 (100 nM) but not by the selective 5-HT1A antagonist WAY 100135 (1 ,M). Other antagonists known to block 5-HT2, 5-HT6 and/or 5-HT7 receptors (ketanserin, RO 04-6790, ritanserin and clozapine) did not change the effect of the agonists. The data suggest an important contribution of 5-HT1B receptors to the inhibition of spinal C-fibre mediated nociceptive reflexes but no experimental support was found for the intervention of 5-HT2, 5-HT6 or 5-HT7 receptors in this in vitro model. British Journal of Pharmacology (2002) 135, 935,942; doi:10.1038/sj.bjp.0704526 [source] Ligand-Gated Synthetic Ion ChannelsCHEMISTRY - A EUROPEAN JOURNAL, Issue 22 2005Pinaki Talukdar Abstract Supramolecular ,-stack architecture is fundamental in DNA chemistry but absent in biological and synthetic ion channels and pores. Here, a novel rigid-rod ,-stack architecture is introduced to create synthetic ion channels with characteristics that are at the forefront of rational design, that is, ligand gating by a conformational change of the functional supramolecule. Namely, the intercalation of electron-rich aromatics is designed to untwist inactive electron-poor helical ,-stacks without internal space into open barrel-stave ion channels. Conductance experiments in planar lipid bilayers corroborate results from spherical bilayers and molecular modeling: Highly cooperative and highly selective ligand gating produces small, long-lived, weakly anion selective, ohmic ion channels. Structural studies conducted under conditions relevant for function provide experimental support for helix,barrel transition as origin of ligand gating. Control experiments demonstrate that minor structural changes leading to internal decrowding suffice to cleanly annihilate chiral self-organization and function. [source] | ||||||||||||||||