Modelling negative feedback networks for activating transcription factor 3 predicts a dominant role for miRNAs in immediate early gene regulation

Activating transcription factor 3 (Atf3) is rapidly and transiently upregulated in numerous systems, and is associated with various disease states. Atf3 is required for negative feedback regulation of other genes, but is itself subject to negative feedback regulation possibly by autorepression. In cardiomyocytes, Atf3 and Egr1 mRNAs are upregulated via ERK1/2 signalling and Atf3 suppresses Egr1 expression. We previously developed a mathematical model for the Atf3-Egr1 system. Here, we adjusted and extended the model to explore mechanisms of Atf3 feedback regulation. Introduction of an autorepressive loop for Atf3 tuned down its expression and inhibition of Egr1 was lost, demonstrating that negative feedback regulation of Atf3 by Atf3 itself is implausible in this context. Experimentally, signals downstream from ERK1/2 suppress Atf3 expression. Mathematical modelling indicated that this cannot occur by phosphorylation of pre-existing inhibitory transcriptional regulators because the time delay is too short. De novo synthesis of an inhibitory transcription factor (ITF) with a high affinity for the Atf3 promoter could suppress Atf3 expression, but (as with the Atf3 autorepression loop) inhibition of Egr1 was lost. Developing the model to include newly-synthesised miRNAs very efficiently terminated Atf3 protein expression and, with a 4-fold increase in the rate of degradation of mRNA from the mRNA/miRNA complex, profiles for Atf3 mRNA, Atf3 protein and Egr1 mRNA approximated to the experimental data. Combining the ITF model with that of the miRNA did not improve the profiles suggesting that miRNAs are likely to play a dominant role in switching off Atf3 expression post-induction.

Differential interference effects of negative emotional states on subsequent semantic and perceptual processing

Past studies have revealed that encountering negative events interferes with cognitive processing of subsequent stimuli. The present study investigates whether negative events affect semantic and perceptual processing differently. Presentation of negative pictures produced slower reaction times than neutral or positive pictures in tasks that require semantic processing, such as natural or man-made judgments about drawings of objects, commonness judgments about objects, and categorical judgments about pairs of words. In contrast, negative picture presentation did not slow down judgments in subsequent perceptual processing (e.g., color judgments about words, size judgments about objects). The subjective arousal level of negative pictures did not modulate the interference effects on semantic or perceptual processing. These findings indicate that encountering negative emotional events interferes with semantic processing of subsequent stimuli more strongly than perceptual processing, and that not all types of subsequent cognitive processing are impaired by negative events.

Impairments in glucose tolerance can have a negative impact on cognitive function: a systematic research review

There is an increasing body of research investigating whether abnormal glucose tolerance is associated with cognitive impairments, the evidence from which is equivocal. A systematic search of the literature identified twenty-three studies which assessed either clinically defined impaired glucose tolerance (IGT) or variance in glucose tolerance within the clinically defined normal range (NGT). The findings suggest that poor glucose tolerance is associated with cognitive impairments, with decrements in verbal memory being most prevalent. However, the evidence for decrements in other domains was weak. The NGT studies report a stronger glucose tolerance-cognition association than the IGT studies, which is likely to be due to the greater number of glucose tolerance parameters and the more sensitive cognitive tests in the NGT studies compared to the IGT studies. It is also speculated that the negative cognitive impact of abnormalities in glucose tolerance increases with age, and that glucose consumption is most beneficial to individuals with poor glucose tolerance compared to individuals with normal glucose tolerance. The role of potential mechanisms are discussed.

Nature of autobiographical memory that facilitates improvement of negative moods

Sakaki, M. (2005). Persons in negative moods often recall their positive experiences to alleviate their affective states. This study investigated the nature of autobiographical memories that facilitate improvement of negative moods. More specifically, it examined the relations between participants' subjective moods and the three natures of recalled memories (the current positivity, the past positivity, and the importance). After 67 participants were induced either negative or neutral moods, they were asked to recall five positive experiences and to rate their affective states. Results indicated that the more important memories participants recalled, the more positive moods they reported after recollection, and that these effects of the importance of autobiographical memories were observed in both negative and neutral moods. In contrast, neither the current positivity of memories nor the past positivity of memories significantly influenced participant's moods in both negative and neutral moods. The mechanism by which the importance of autobiographical memory affects moods was discussed.

Statistical-dynamical downscaling for wind energy potentials: evaluation and applications to decadal hindcasts and climate change projections

A statistical–dynamical downscaling (SDD) approach for the regionalization of wind energy output (Eout) over Europe with special focus on Germany is proposed. SDD uses an extended circulation weather type (CWT) analysis on global daily mean sea level pressure fields with the central point being located over Germany. Seventy-seven weather classes based on the associated CWT and the intensity of the geostrophic flow are identified. Representatives of these classes are dynamically downscaled with the regional climate model COSMO-CLM. By using weather class frequencies of different data sets, the simulated representatives are recombined to probability density functions (PDFs) of near-surface wind speed and finally to Eout of a sample wind turbine for present and future climate. This is performed for reanalysis, decadal hindcasts and long-term future projections. For evaluation purposes, results of SDD are compared to wind observations and to simulated Eout of purely dynamical downscaling (DD) methods. For the present climate, SDD is able to simulate realistic PDFs of 10-m wind speed for most stations in Germany. The resulting spatial Eout patterns are similar to DD-simulated Eout. In terms of decadal hindcasts, results of SDD are similar to DD-simulated Eout over Germany, Poland, Czech Republic, and Benelux, for which high correlations between annual Eout time series of SDD and DD are detected for selected hindcasts. Lower correlation is found for other European countries. It is demonstrated that SDD can be used to downscale the full ensemble of the Earth System Model of the Max Planck Institute (MPI-ESM) decadal prediction system. Long-term climate change projections in Special Report on Emission Scenarios of ECHAM5/MPI-OM as obtained by SDD agree well to the results of other studies using DD methods, with increasing Eout over northern Europe and a negative trend over southern Europe. Despite some biases, it is concluded that SDD is an adequate tool to assess regional wind energy changes in large model ensembles.

Probabilistic parameterisation of the surface mass balance--elevation feedback in regional climate model simulations of the Greenland ice sheet

We present a new parameterisation that relates surface mass balance (SMB: the sum of surface accumulation and surface ablation) to changes in surface elevation of the Greenland ice sheet (GrIS) for the MAR (Modèle Atmosphérique Régional: Fettweis, 2007) regional climate model. The motivation is to dynamically adjust SMB as the GrIS evolves, allowing us to force ice sheet models with SMB simulated by MAR while incorporating the SMB–elevation feedback, without the substantial technical challenges of coupling ice sheet and climate models. This also allows us to assess the effect of elevation feedback uncertainty on the GrIS contribution to sea level, using multiple global climate and ice sheet models, without the need for additional, expensive MAR simulations. We estimate this relationship separately below and above the equilibrium line altitude (ELA, separating negative and positive SMB) and for regions north and south of 77� N, from a set of MAR simulations in which we alter the ice sheet surface elevation. These give four “SMB lapse rates”, gradients that relate SMB changes to elevation changes. We assess uncertainties within a Bayesian framework, estimating probability distributions for each gradient from which we present best estimates and credibility intervals (CI) that bound 95% of the probability. Below the ELA our gradient estimates are mostly positive, because SMB usually increases with elevation: 0.56 (95% CI: −0.22 to 1.33) kgm−3 a−1 for the north, and 1.91 (1.03 to 2.61) kgm−3 a−1 for the south. Above the ELA, the gradients are much smaller in magnitude: 0.09 (−0.03 to 0.23) kgm−3 a−1 in the north, and 0.07 (−0.07 to 0.59) kgm−3 a−1 in the south, because SMB can either increase or decrease in response to increased elevation. Our statistically founded approach allows us to make probabilistic assessments for the effect of elevation feedback uncertainty on sea level projections (Edwards et al., 2014).

Occurrence probability, width and number of steps of cusp precipitation for fully pulsed reconnection at the dayside magnetopause

We discuss the characteristics of magnetosheath plasma precipitation in the “cusp” ionosphere for when the reconnection at the dayside magnetopause takes place only in a series of pulses. It is shown that even in this special case, the low-altitude cusp precipitation is continuous, unless the intervals between the pulses are longer than observed intervals between magnetopause flux transfer event (FTE) signatures. We use FTE observation statistics to predict, for this case of entirely pulsed reconnection, the occurrence frequency, the distribution of latitudinal widths, and the number of ion dispersion steps of the cusp precipitation for a variety of locations of the reconnection site and a range of values of the local de-Hoffman Teller velocity. It is found that the cusp occurrence frequency is comparable with observed values for virtually all possible locations of the reconnection site. The distribution of cusp width is also comparable with observations and is shown to be largely dependent on the distribution of the mean reconnection rate, but pulsing the reconnection does very slightly increase the width of that distribution compared with the steady state case. We conclude that neither cusp occurrence probability nor width can be used to evaluate the relative occurrence of reconnection behaviors that are entirely pulsed, pulsed but continuous and quasi-steady. We show that the best test of the relative frequency of these three types of reconnection is to survey the distribution of steps in the cusp ion dispersion characteristics.

Probability functions to build composite indicators: a methodology to measure environmental impacts of genetically modified crops

There is an on-going debate on the environmental effects of genetically modified crops to which this paper aims to contribute. First, data on environmental impacts of genetically modified (GM) and conventional crops are collected from peer-reviewed journals, and secondly an analysis is conducted in order to examine which crop type is less harmful for the environment. Published data on environmental impacts are measured using an array of indicators, and their analysis requires their normalisation and aggregation. Taking advantage of composite indicators literature, this paper builds composite indicators to measure the impact of GM and conventional crops in three dimensions: (1) non-target key species richness, (2) pesticide use, and (3) aggregated environmental impact. The comparison between the three composite indicators for both crop types allows us to establish not only a ranking to elucidate which crop is more convenient for the environment but the probability that one crop type outperforms the other from an environmental perspective. Results show that GM crops tend to cause lower environmental impacts than conventional crops for the analysed indicators.

Negative online consumer reviews: effects of different responses

Purpose When consumers buy online, they are often confronted with consumer reviews. A negative consumer review on an online shopping website may keep consumers from buying the product. Therefore, negative online consumer reviews are a serious problem for brands. This paper aims to investigate the effects of different response options to a negative consumer review. Design/methodology/approach In an online experiment of 446 participants different response options towards a negative consumer review on an online shopping website are examined. The experimental data is analysed with simple linear regression models using product purchase intentions as the outcome variable. Findings The results indicate that a positive customer review counteracts a negative consumer review more effectively than a positive brand response, whereas brand strength moderates this relationship. Including a reference to an independent, trusted source in a brand or a customer response is only a limited strategy for increasing the effectiveness of a response. Research limitations/implications Additional research in other product categories and with other subjects than students is suggested to validate the findings. In future research, multiple degrees of the phrasing’s strength of the reference could be used. Practical implications Assuming high quality products, brands should encourage their customers to write reviews. Strong brands can also reassure consumers by responding whereas weak brands cannot. Originality/value This research contributes to the online consumer reviews literature with new insights about the role of brand strength and referencing to an independent, trusted source.

An evaluation of decadal probability forecasts from state-of-the-art climate models

While state-of-the-art models of Earth's climate system have improved tremendously over the last 20 years, nontrivial structural flaws still hinder their ability to forecast the decadal dynamics of the Earth system realistically. Contrasting the skill of these models not only with each other but also with empirical models can reveal the space and time scales on which simulation models exploit their physical basis effectively and quantify their ability to add information to operational forecasts. The skill of decadal probabilistic hindcasts for annual global-mean and regional-mean temperatures from the EU Ensemble-Based Predictions of Climate Changes and Their Impacts (ENSEMBLES) project is contrasted with several empirical models. Both the ENSEMBLES models and a “dynamic climatology” empirical model show probabilistic skill above that of a static climatology for global-mean temperature. The dynamic climatology model, however, often outperforms the ENSEMBLES models. The fact that empirical models display skill similar to that of today's state-of-the-art simulation models suggests that empirical forecasts can improve decadal forecasts for climate services, just as in weather, medium-range, and seasonal forecasting. It is suggested that the direct comparison of simulation models with empirical models becomes a regular component of large model forecast evaluations. Doing so would clarify the extent to which state-of-the-art simulation models provide information beyond that available from simpler empirical models and clarify current limitations in using simulation forecasting for decision support. Ultimately, the skill of simulation models based on physical principles is expected to surpass that of empirical models in a changing climate; their direct comparison provides information on progress toward that goal, which is not available in model–model intercomparisons.

Probabilistic skill in ensemble seasonal forecasts

Simulation models are widely employed to make probability forecasts of future conditions on seasonal to annual lead times. Added value in such forecasts is reflected in the information they add, either to purely empirical statistical models or to simpler simulation models. An evaluation of seasonal probability forecasts from the Development of a European Multimodel Ensemble system for seasonal to inTERannual prediction (DEMETER) and ENSEMBLES multi-model ensemble experiments is presented. Two particular regions are considered: Nino3.4 in the Pacific and the Main Development Region in the Atlantic; these regions were chosen before any spatial distribution of skill was examined. The ENSEMBLES models are found to have skill against the climatological distribution on seasonal time-scales. For models in ENSEMBLES that have a clearly defined predecessor model in DEMETER, the improvement from DEMETER to ENSEMBLES is discussed. Due to the long lead times of the forecasts and the evolution of observation technology, the forecast-outcome archive for seasonal forecast evaluation is small; arguably, evaluation data for seasonal forecasting will always be precious. Issues of information contamination from in-sample evaluation are discussed and impacts (both positive and negative) of variations in cross-validation protocol are demonstrated. Other difficulties due to the small forecast-outcome archive are identified. The claim that the multi-model ensemble provides a ‘better’ probability forecast than the best single model is examined and challenged. Significant forecast information beyond the climatological distribution is also demonstrated in a persistence probability forecast. The ENSEMBLES probability forecasts add significantly more information to empirical probability forecasts on seasonal time-scales than on decadal scales. Current operational forecasts might be enhanced by melding information from both simulation models and empirical models. Simulation models based on physical principles are sometimes expected, in principle, to outperform empirical models; direct comparison of their forecast skill provides information on progress toward that goal.

Comments on 'Current GCMs' Unrealistic Negative Feedback in the Arctic'

In contrast to prior studies showing a positive lapse-rate feedback associated with the Arctic inversion, Boé et al. reported that strong present-day Arctic temperature inversions are associated with stronger negative longwave feedbacks and thus reduced Arctic amplification in the model ensemble from phase 3 of the Coupled Model Intercomparison Project (CMIP3). A permutation test reveals that the relation between longwave feedbacks and inversion strength is an artifact of statistical self-correlation and that shortwave feedbacks have a stronger correlation with intermodel spread. The present comment concludes that the conventional understanding of a positive lapse-rate feedback associated with the Arctic inversion is consistent with the CMIP3 model ensemble.

Estimation of Gaussian process regression model using probability distance measures

A new class of parameter estimation algorithms is introduced for Gaussian process regression (GPR) models. It is shown that the integration of the GPR model with probability distance measures of (i) the integrated square error and (ii) Kullback–Leibler (K–L) divergence are analytically tractable. An efficient coordinate descent algorithm is proposed to iteratively estimate the kernel width using golden section search which includes a fast gradient descent algorithm as an inner loop to estimate the noise variance. Numerical examples are included to demonstrate the effectiveness of the new identification approaches.

Long-latency reductions in gamma power predict hemodynamic changes that underlie the negative BOLD signal

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.

The probability of sale and price premiums in withdrawn auctioned properties

This paper examines the impact of the auction process of residential properties that whilst unsuccessful at auction sold subsequently. The empirical analysis considers both the probability of sale and the premium of the subsequent sale price over the guide price, reserve and opening bid. The findings highlight that the final achieved sale price is influenced by key price variables revealed both prior to and during the auction itself. Factors such as auction participation, the number of individual bidders and the number of bids are significant in a number of the alternative specifications.