51 resultados para Dependent Conformational-changes


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Temporal discounting (TD) matures with age, alongside other markers of increased impulse control, and coherent, self-regulated behaviour. Discounting paradigms quantify the ability to refrain from preference of immediate rewards, in favour of delayed, larger rewards. As such, they measure temporal foresight and the ability to delay gratification, functions that develop slowly into adulthood. We investigated the neural maturation that accompanies the previously observed age-related behavioural changes in discounting, from early adolescence into mid-adulthood. We used functional magnetic resonance imaging of a hypothetical discounting task with monetary rewards delayed in the week to year range. We show that age-related reductions in choice impulsivity were associated with changes in activation in ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), ventral striatum (VS), insula, inferior temporal gyrus, and posterior parietal cortex. Limbic frontostriatal activation changes were specifically associated with age-dependent reductions in impulsive choice, as part of a more extensive network of brain areas showing age-related changes in activation, including dorsolateral PFC, inferior parietal cortex, and subcortical areas. The maturational pattern of functional connectivity included strengthening in activation coupling between ventromedial and dorsolateral PFC, parietal and insular cortices during selection of delayed alternatives, and between vmPFC and VS during selection of immediate alternatives. We conclude that maturational mechanisms within limbic frontostriatal circuitry underlie the observed post-pubertal reductions in impulsive choice with increasing age, and that this effect is dependent on increased activation coherence within a network of areas associated with discounting behaviour and inter-temporal decision-making.

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The addition of oligofructose as a dietary fiber decreases the serum concentration and the hepatic release of VLDL-triglycerides in rats. Because glucose, insulin, insulin-like growth factor I (IGF-I) and gut peptides [i.e., glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)]) are factors involved in the metabolic response to nutrients, this paper analyzes their putative role in the hypolipidemic effect of oligofructose. Male Wistar rats were fed a nonpurified diet with or without 10% oligofructose for 30 d. Glucose, insulin, IGF-I and GIP concentrations were measured in the serum of rats after eating. GIP and GLP-1 contents were also assayed in small intestine and cecal extracts, respectively. A glucose tolerance test was performed in food-deprived rats. Serum insulin level was significantly lower in oligofructose-fed rats both after eating and in the glucose tolerance test, whereas glycemia was lower only in the postprandial state. IGF-I serum level did not differ between groups. GIP concentration was significantly higher in the serum of oligofructose-fed rats. The GLP-1 cecal pool was also significantly higher. In this study, we have shown that cecal proliferation induced by oligofructose leads to an increase in GLP-1 concentration. This latter incretin could be involved in the maintenance of glycemia despite a lower insulinemia in the glucose tolerance test in oligofructose-fed rats. We discuss also the role of hormonal changes in the antilipogenic effect of oligofructose.

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Obstacles considerably influence boundary layer processes. Their influences have been included in mesoscale models (MeM) for a long time. Methods used to parameterise obstacle effects in a MeM are summarised in this paper using results of the mesoscale model METRAS as examples. Besides the parameterisation of obstacle influences it is also possible to use a joint modelling approach to describe obstacle induced and mesoscale changes. Three different methods may be used for joint modelling approaches: The first method is a time-slice approach, where steady basic state profiles are used in an obstacle resolving microscale model (MiM, example model MITRAS) and diurnal cycles are derived by joining steady-state MITRAS results. The second joint modelling approach is one-way nesting, where the MeM results are used to initialise the MiM and to drive the boundary values of the MiM dependent on time. The third joint modelling approach is to apply multi-scale models or two-way nesting approaches, which include feedbacks from the MiM to the MeM. The advantages and disadvantages of the different approaches and remaining problems with joint Reynolds-averaged Navier–Stokes modelling approaches are summarised in the paper.

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Satellite measurements of the radiation budget and data from the U.S. National Centers for Environmental Prediction–National Center for Atmospheric Research reanalysis are used to investigate the links between anomalous cloud radiative forcing over the tropical west Pacific warm pool and the tropical dynamics and sea surface temperature (SST) distribution during 1998. The ratio, N, of the shortwave cloud forcing (SWCF) to longwave cloud forcing (LWCF) (N = −SWCF/LWCF) is used to infer information on cloud altitude. A higher than average N during 1998 appears to be related to two separate phenomena. First, dynamic regime-dependent changes explain high values of N (associated with low cloud altitude) for small magnitudes of SWCF and LWCF (low cloud fraction), which reflect the unusual occurrence of mean subsiding motion over the tropical west Pacific during 1998, associated with the anomalous SST distribution. Second, Tropics-wide long-term changes in the spatial-mean cloud forcing, independent of dynamic regime, explain the higher values of N during both 1998 and in 1994/95. The changes in dynamic regime and their anomalous structure in 1998 are well simulated by version HadAM3 of the Hadley Centre climate model, forced by the observed SSTs. However, the LWCF and SWCF are poorly simulated, as are the interannual changes in N. It is argued that improved representation of LWCF and SWCF and their dependence on dynamical forcing are required before the cloud feedbacks simulated by climate models can be trusted.

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A time-dependent climate-change experiment with a coupled ocean–atmosphere general circulation model has been used to study changes in the occurrence of drought in summer in southern Europe and central North America. In both regions, precipitation and soil moisture are reduced in a climate of greater atmospheric carbon dioxide. A detailed investigation of the hydrology of the model shows that the drying of the soil comes about through an increase in evaporation in winter and spring, caused by higher temperatures and reduced snow cover, and a decrease in the net input of water in summer. Evaporation is reduced in summer because of the drier soil, but the reduction in precipitation is larger. Three extreme statistics are used to define drought, namely the frequency of low summer precipitation, the occurrence of long dry spells, and the probability of dry soil. The last of these is arguably of the greatest practical importance, but since it is based on soil moisture, of which there are very few observations, the authors’ simulation of it has the least confidence. Furthermore, long time series for daily observed precipitation are not readily available from a sufficient number of stations to enable a thorough evaluation of the model simulation, especially for the frequency of long dry spells, and this increases the systematic uncertainty of the model predictions. All three drought statistics show marked increases owing to the sensitivity of extreme statistics to changes in their distributions. However, the greater likelihood of long dry spells is caused by a tendency in the character of daily rainfall toward fewer events, rather than by the reduction in mean precipitation. The results should not be taken as firm predictions because extreme statistics for small regions cannot be calculated reliably from the output of the current generation of GCMs, but they point to the possibility of large increases in the severity of drought conditions as a consequence of climate change caused by increased CO2.

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This article applies a three-regime Markov switching model to investigate the impact of the macroeconomy on the dynamics of the residential real estate market in the US. Focusing on the period between 1960 and 2011, the methodology implemented allows for a clearer understanding of the drivers of the real estate market in “boom”, “steady-state” and “crash” regimes. Our results show that the sensitivity of the real estate market to economic changes is regime-dependent. The paper then proceeds to examine whether policymakers are able to influence a regime switch away from the crash regime. We find that a decrease in interest rate spreads could be an effective catalyst to precipitate such a change of state.

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Synoptic activity over the Northern Hemisphere is evaluated in ensembles of ECHAM5/MPI-OM1 simulations for recent climate conditions (20C) and for three climate scenarios (following SRES A1B, A2, B1). A close agreement is found between the simulations for present day climate and the respective results from reanalysis. Significant changes in the winter mid-tropospheric storm tracks are detected in all three scenario simulations. Ensemble mean climate signals are rather similar, with particularly large activity increases downstream of the Atlantic storm track over Western Europe. The magnitude of this signal is largely dependent on the imposed change in forcing. However, differences between individual ensemble members may be large. With respect to the surface cyclones, the scenario runs produce a reduction in cyclonic track density over the mid-latitudes, even in the areas with increasing mid-tropospheric activity. The largest decrease in track densities occurs at subtropical latitudes, e.g., over the Mediterranean Basin. An increase of cyclone intensities is detected for limited areas (e.g., near Great Britain and Aleutian Isles) for the A1B and A2 experiments. The changes in synoptic activity are associated with alterations of the Northern Hemisphere circulation and background conditions (blocking frequencies, jet stream). The North Atlantic Oscillation index also shows increased values with enhanced forcing. With respect to the effects of changing synoptic activity, the regional change in cyclone intensities is accompanied by alterations of the extreme surface winds, with increasing values over Great Britain, North and Baltic Seas, as well as the areas with vanishing sea ice, and decreases over much of the subtropics.

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Accurate co-ordination of accommodation and convergence is necessary to view near objects and develop fine motor co-ordination. We used a remote haploscopic videorefraction paradigm to measure longitudinal changes in simultaneous ocular accommodation and vergence to targets at different depths, and to all combinations of blur, binocular disparity, and change-in-size (“proximity”) cues. Infants were followed longitudinally and compared to older children and young adults, with the prediction that sensitivity to different cues would change during development. Mean infant responses to the most naturalistic condition were similar to those of adults from 6-7 weeks (accommodation) and 8-9 weeks (vergence). Proximity cues influenced responses most in infants less than 14 weeks of age, but sensitivity declined thereafter. Between 12-28 weeks of age infants were equally responsive to all three cues, while in older children and adults manipulation of disparity resulted in the greatest changes in response. Despite rapid development of visual acuity (thus increasing availability of blur cues), responses to blur were stable throughout development. Our results suggest that during much of infancy, vergence and accommodation responses are not dependent on the development of specific depth cues, but make use of any cues available to drive appropriate changes in response.

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It is well known that there is a dynamic relationship between cerebral blood flow (CBF) and cerebral blood volume (CBV). With increasing applications of functional MRI, where the blood oxygen-level-dependent signals are recorded, the understanding and accurate modeling of the hemodynamic relationship between CBF and CBV becomes increasingly important. This study presents an empirical and data-based modeling framework for model identification from CBF and CBV experimental data. It is shown that the relationship between the changes in CBF and CBV can be described using a parsimonious autoregressive with exogenous input model structure. It is observed that neither the ordinary least-squares (LS) method nor the classical total least-squares (TLS) method can produce accurate estimates from the original noisy CBF and CBV data. A regularized total least-squares (RTLS) method is thus introduced and extended to solve such an error-in-the-variables problem. Quantitative results show that the RTLS method works very well on the noisy CBF and CBV data. Finally, a combination of RTLS with a filtering method can lead to a parsimonious but very effective model that can characterize the relationship between the changes in CBF and CBV.

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The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen level-dependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBV proportional to CBFPhi has been used extensively in the literature. Two similar models, the Balloon (Buxton et al., 1998) and the Windkessel (Mandeville et al., 1999), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

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Although promise exists for patterns of resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) brain connectivity to be used as biomarkers of early brain pathology, a full understanding of the nature of the relationship between neural activity and spontaneous fMRI BOLD fluctuations is required before such data can be correctly interpreted. To investigate this issue, we combined electrophysiological recordings of rapid changes in multi-laminar local field potentials from the somatosensory cortex of anaesthetized rats with concurrent two-dimensional optical imaging spectroscopy measurements of resting-state haemodynamics that underlie fluctuations in the BOLD fMRI signal. After neural ‘events’ were identified, their time points served to indicate the start of an epoch in the accompanying haemodynamic fluctuations. Multiple epochs for both neural ‘events’ and the accompanying haemodynamic fluctuations were averaged. We found that the averaged epochs of resting-state haemodynamic fluctuations taken after neural ‘events’ closely resembled the temporal profile of stimulus-evoked cortical haemodynamics. Furthermore, we were able to demonstrate that averaged epochs of resting-state haemodynamic fluctuations resembling the temporal profile of stimulus-evoked haemodynamics could also be found after peaks in neural activity filtered into specific electroencephalographic frequency bands (theta, alpha, beta, and gamma). This technique allows investigation of resting-state neurovascular coupling using methodologies that are directly comparable to that developed for investigating stimulus-evoked neurovascular responses.

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Background and Purpose. In rat middle cerebral arteries, endothelium-dependent hyperpolarization (EDH) is mediated by activation of calcium-activated potassium(KCa) channels specifically KCa2.3 and KCa3.1. Lipoxygenase (LOX) products function as endothelium-derived hyperpolarizing factors (EDHFs) in rabbit arteries by stimulating KCa2.3. We investigated if LOX products contribute to EDH in rat cerebral arteries. Methods. Arachidonic acid (AA) metabolites produced in middle cerebral arteries were measured using HPLC and LC/MS. Vascular tension and membrane potential responses to SLIGRL were simultaneously recorded using wire myography and intracellular microelectrodes. Results. SLIGRL, an agonist at PAR2 receptors, caused EDH that was inhibited by a combination of KCa2.3 and KCa3.1 blockade. Non-selective LOX-inhibition reduced EDH, whereas inhibition of 12-LOX had no effect. Soluble epoxide hydrolase (sEH) inhibition enhanced the KCa2.3 component of EDH. Following NO synthase (NOS) inhibition, the KCa2.3 component of EDH was absent. Using HPLC, middle cerebral arteries metabolized 14C-AA to 15- and 12-LOX products under control conditions. With NOS inhibition, there was little change in LOX metabolites, but increased F-type isoprostanes. 8-iso-PGF2α inhibited the KCa2.3 component of EDH. Conclusions. LOX metabolites mediate EDH in rat middle cerebral arteries. Inhibition of sEH increases the KCa2.3 component of EDH. Following NOS inhibition,loss of KCa2.3 function is independent of changes in LOX production or sEH inhibition but due to increased isoprostane production and subsequent stimulation of TP receptors. These findings have important implications in diseases associated with loss of NO signaling such as stroke; where inhibition of sEH and/or isoprostane formation may of benefit.

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We apply a numerical model of time-dependent ionospheric convection to two directly driven reconnection pulses during a 15-min interval of southward IMF on 26 November 2000. The model requires an input magnetopause reconnection rate variation, which is here derived from the observed variation in the upstream IMF clock angle, q. The reconnection rate is mapped to an ionospheric merging gap, the MLT extent of which is inferred from the Doppler-shifted Lyman-a emission on newly opened field lines, as observed by the FUV instrument on the IMAGE spacecraft. The model is used to reproduce a variety of features observed during this event: SuperDARN observations of the ionospheric convection pattern and transpolar voltage; FUV observations of the growth of patches of newly opened flux; FUVand in situ observations of the location of the Open-Closed field line Boundary (OCB) and a cusp ion step. We adopt a clock angle dependence of the magnetopause reconnection electric field, mapped to the ionosphere, of the form Enosin4(q/2) and estimate the peak value, Eno, by matching observed and modeled variations of both the latitude, LOCB, of the dayside OCB (as inferred from the equatorward edge of cusp proton emissions seen by FUV) and the transpolar voltage FPC (as derived using the mapped potential technique from SuperDARN HF radar data). This analysis also yields the time constant tOCB with which the open-closed boundary relaxes back toward its equilibrium configuration. For the case studied here, we find tOCB = 9.7 ± 1.3 min, consistent with previous inferences from the observed response of ionospheric flow to southward turnings of the IMF. The analysis confirms quantitatively the concepts of ionospheric flow excitation on which the model is based and explains some otherwise anomalous features of the cusp precipitation morphology.

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The generation of flow and current vortices in the dayside auroral ionosphere has been predicted for two processes ocurring at the dayside magnetopause. The first of these mechanisms is time-dependent magnetic reconnection, in “flux transfer events” (FTEs); the second is the action of solar wind dynamic pressure changes. The ionospheric flow signature of an FTE should be a twin vortex, with the mean flow velocity in the central region of the pattern equal to the velocity of the pattern as a whole. On the other hand, a pulse of enhanced or reduced dynamic pressure is also expected to produce a twin vortex, but with the central plasma flow being generally different in speed from, and almost orthogonal to, the motion of the whole pattern. In this paper, we make use of this distinction to discuss recent observations of vortical flow patterns in the dayside auroral ionosphere in terms of one or other of the proposed mechanisms. We conclude that some of the observations reported are consistent only with the predicted signature of FTEs. We then evaluate the dimensions of the open flux tubes required to explain some recent simultaneous radar and auroral observations and infer that they are typically 300 km in north–south extent but up to 2000 km in longitudinal extent (i.e., roughly 5 hours of MLT). Hence these observations suggest that recent theories of FTEs which invoke time-varying reconnection at an elongated neutral line may be correct. We also present some simultaneous observations of the interplanetary magnetic field (IMF) and solar wind dynamic pressure (observed using the IMP8 satellite) and the ionospheric flow (observed using the EISCAT radar) which are also only consistent with the FTE model. We estimate that for continuously southward IMF ( ≈ 5 nT) these FTEs contribute about 30 kV to the mean total transpolar voltage (∼30%).

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Studiesthat use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to “negative” hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently withtwo-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gammaband power (30 – 80 Hz) in the middle-superficial cortical layers in regions surrounding the activated whisker barrel cortex. This reduction in gamma frequency activity was associated with corresponding decreases in the hemodynamic responses that drive the negative BOLD signal. These findings suggest a close relationship between BOLD responses and neural events that operate over time scales that outlast the initiating sensory stimulus, and provide important insights into the neurophysiological basis of negative neuroimaging signals.