Wavelet transform-based de-noising for two-photon imaging of synaptic Ca2+ transients.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tThis is an open access article.Postsynaptic Ca(2+) transients triggered by neurotransmission at excitatory synapses are a key signaling step for the induction of synaptic plasticity and are typically recorded in tissue slices using two-photon fluorescence imaging with Ca(2+)-sensitive dyes. The signals generated are small with very low peak signal/noise ratios (pSNRs) that make detailed analysis problematic. Here, we implement a wavelet-based de-noising algorithm (PURE-LET) to enhance signal/noise ratio for Ca(2+) fluorescence transients evoked by single synaptic events under physiological conditions. Using simulated Ca(2+) transients with defined noise levels, we analyzed the ability of the PURE-LET algorithm to retrieve the underlying signal. Fitting single Ca(2+) transients with an exponential rise and decay model revealed a distortion of τ(rise) but improved accuracy and reliability of τ(decay) and peak amplitude after PURE-LET de-noising compared to raw signals. The PURE-LET de-noising algorithm also provided a ∼30-dB gain in pSNR compared to ∼16-dB pSNR gain after an optimized binomial filter. The higher pSNR provided by PURE-LET de-noising increased discrimination accuracy between successes and failures of synaptic transmission as measured by the occurrence of synaptic Ca(2+) transients by ∼20% relative to an optimized binomial filter. Furthermore, in comparison to binomial filter, no optimization of PURE-LET de-noising was required for reducing arbitrary bias. In conclusion, the de-noising of fluorescent Ca(2+) transients using PURE-LET enhances detection and characterization of Ca(2+) responses at central excitatory synapses.C.M.T. and J.R.M. were supported by the Wellcome Trust, and K.T.-A. was supported by grant No. EP/I018638/1 from the Engineering and Physical Sciences Research Council

Increased insolation threshold for runaway greenhouse processes on Earth like planets

Because the solar luminosity increases over geological timescales, Earth climate is expected to warm, increasing water evaporation which, in turn, enhances the atmospheric greenhouse effect. Above a certain critical insolation, this destabilizing greenhouse feedback can "runaway" until all the oceans are evaporated. Through increases in stratospheric humidity, warming may also cause oceans to escape to space before the runaway greenhouse occurs. The critical insolation thresholds for these processes, however, remain uncertain because they have so far been evaluated with unidimensional models that cannot account for the dynamical and cloud feedback effects that are key stabilizing features of Earth's climate. Here we use a 3D global climate model to show that the threshold for the runaway greenhouse is about 375 W/m$^2$, significantly higher than previously thought. Our model is specifically developed to quantify the climate response of Earth-like planets to increased insolation in hot and extremely moist atmospheres. In contrast with previous studies, we find that clouds have a destabilizing feedback on the long term warming. However, subsident, unsaturated regions created by the Hadley circulation have a stabilizing effect that is strong enough to defer the runaway greenhouse limit to higher insolation than inferred from 1D models. Furthermore, because of wavelength-dependent radiative effects, the stratosphere remains cold and dry enough to hamper atmospheric water escape, even at large fluxes. This has strong implications for Venus early water history and extends the size of the habitable zone around other stars.Comment: Published in Nature. Online publication date: December 12, 2013. Accepted version before journal editing and with Supplementary Informatio

Energy- and flux-budget (EFB) turbulence closure model for the stably stratified flows. Part I: Steady-state, homogeneous regimes

We propose a new turbulence closure model based on the budget equations for the key second moments: turbulent kinetic and potential energies: TKE and TPE (comprising the turbulent total energy: TTE = TKE + TPE) and vertical turbulent fluxes of momentum and buoyancy (proportional to potential temperature). Besides the concept of TTE, we take into account the non-gradient correction to the traditional buoyancy flux formulation. The proposed model grants the existence of turbulence at any gradient Richardson number, Ri. Instead of its critical value separating - as usually assumed - the turbulent and the laminar regimes, it reveals a transition interval, 0.1< Ri <1, which separates two regimes of essentially different nature but both turbulent: strong turbulence at Ri<<1; and weak turbulence, capable of transporting momentum but much less efficient in transporting heat, at Ri>1. Predictions from this model are consistent with available data from atmospheric and lab experiments, direct numerical simulation (DNS) and large-eddy simulation (LES).Comment: 40 pages, 6 figures, Boundary-layer Meteorology, resubmitted, revised versio

Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

Heat and moisture budgets from airborne measurements and high-resolution model simulations

High-resolution simulations with a mesoscale model are performed to estimate heat and moisture budgets of a well-mixed boundary layer. The model budgets are validated against energy budgets obtained from airborne measurements over heterogeneous terrain in Western Germany. Time rate of change, vertical divergence, and horizontal advection for an atmospheric column of air are estimated. Results show that the time trend of specific humidity exhibits some deficiencies, while the potential temperature trend is matched accurately. Furthermore, the simulated turbulent surface fluxes of sensible and latent heat are comparable to the measured fluxes, leading to similar values of the vertical divergence. The analysis of different horizontal model resolutions exhibits improved surface fluxes with increased resolution, a fact attributed to a reduced aggregation effect. Scale-interaction effects could be identified: while time trends and advection are strongly influenced by mesoscale forcing, the turbulent surface fluxes are mainly controlled by microscale processes

I Me Mine: on a Confusion Concerning the Subjective Character of Experience

In recent debates on phenomenal consciousness, a distinction is sometimes made, after Levine (2001) and Kriegel (2009), between the “qualitative character” of an experience, i.e. the specific way it feels to the subject (e.g. blueish or sweetish or pleasant), and its “subjective character”, i.e. the fact that there is anything at all that it feels like to her. I argue that much discussion of subjective character is affected by a conflation between three different notions. I start by disentangling the three notions in question, under the labels of “for-me-ness”, “me-ness” and “mineness”. Next, I argue that these notions are not equivalent; in particular, there is no conceptual implication from for-me-ness to me-ness or mineness. Empirical considerations based on clinical cases additionally suggest that the three notions may also correspond to different properties (although the claim of conceptual non-equivalence does not depend on this further point). The aim is clarificatory, cautionary but also critical: I examine four existing arguments from subjective character that are fuelled by an undifferentiated use of the three notions, and find them to be flawed for this reason

Dominant features in three-dimensional turbulence structure: comparison of non-uniform accelerating and decelerating flows

The results are presented from an experimental study to investigate three-dimensional turbulence structure profiles, including turbulence intensity and Reynolds stress, of different non-uniform open channel flows over smooth bed in subcritical flow regime. In the analysis, the uniform flow profiles have been used to compare with those of the non-uniform flows to investigate their time-averaged spatial flow turbulence structure characteristics. The measured non-uniform velocity profiles are used to verify the von Karman constant κ and to estimate sets of log-law integration constant B r and wake parameter П, where their findings are also compared with values from previous studies. From κ, B r and П findings, it has been found that the log-wake law can sufficiently represent the non-uniform flow in its non-modified form, and all κ, B r and П follow universal rules for different bed roughness conditions. The non-uniform flow experiments also show that both the turbulence intensity and Reynolds stress are governed well by exponential pressure gradient parameter β equations. Their exponential constants are described by quadratic functions in the investigated β range. Through this experimental study, it has been observed that the decelerating flow shows higher empirical constants, in both the turbulence intensity and Reynolds stress compared to the accelerating flow. The decelerating flow also has stronger dominance to determine the flow non-uniformity, because it presents higher Reynolds stress profile than uniform flow, whereas the accelerating flow does not

Numerical study of circulation on the inner Amazon Shelf

Author Posting. © Springer, 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ocean Dynamics 58 (2008): 187-198, doi:10.1007/s10236-008-0139-4.We studied the circulation on the coastal domain of the Amazon Shelf by applying the hydrodynamic module of the Estuarine and Coastal Ocean Model and Sediment Transport - ECOMSED. The first barotropic experiment aimed to explain the major bathymetric effects on tides and those generated by anisotropy in sediment distribution. We analyzed the continental shelf response of barotropic tides under realistic bottom stress parametrization (Cd), considering sediment granulometry obtained from a faciologic map, where river mud deposits and reworked sediments areas are well distinguished, among others classes of sediments. Very low Cd values were set in the fluid mud regions off the Amapa coast (1.0 10-4 ), in contrast to values around 3:5 10-3 for coarser sediment regions off the Para coast. Three-dimensional experiments represented the Amazon River discharge and trade winds, combined to barotropic tide influences and induced vertical mixing. The quasi-resonant response of the Amazon Shelf to the M2 tide act on the local hydrodynamics by increasing tidal admittance, along with tidal forcing at the shelf break and extensive fluid mud regions. Harmonic analysis of modeled currents agreed well with analysis of the AMASSEDS observational data set. Tidal-induced vertical shear provided strong homogenization of threshold waters, which are subject to a kind of hydraulic control due to the topographic steepness. Ahead of the hydraulic jump, the low-salinity plume is disconnected from the bottom and acquires negative vorticity, turning southeastward. Tides act as a generator mechanism and topography, via hydraulic control, as a maintainer mechanism for the low-salinity frontal zone positioning. Tidally induced southeastward plume fate is overwhelmed by northwestward trade winds so that, along with background circulation, probably play the most important role on the plume fate and variability over the Amazon Shelf