38 research outputs found

    TCSA and the finite volume boundary state

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    We develop a new way to calculate the overlap of a boundary state with a finite volume bulk state in the truncated conformal space approach. We check this method in the thermally perturbed Ising model analytically, while in the scaling Lee-Yang model numerically by comparing our results to excited state g-functions, which we obtained by the analytical continuation method. We also give a simple argument for the structure of the asymptotic overlap between the finite volume boundary state and a periodic multiparticle state, which includes the ratio of Gaudin type determinants.Comment: 29 pages, 15 figures, v2: typos corrected, comments added, references update

    Verification of alternative splicing variants based on domain integrity, truncation length and intrinsic protein disorder

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    According to current estimations ∼95% of multi-exonic human protein-coding genes undergo alternative splicing (AS). However, for 4000 human proteins in PDB, only 14 human proteins have structures of at least two alternative isoforms. Surveying these structural isoforms revealed that the maximum insertion accommodated by an isoform of a fully ordered protein domain was 5 amino acids, other instances of domain changes involved intrinsic structural disorder. After collecting 505 minor isoforms of human proteins with evidence for their existence we analyzed their length, protein disorder and exposed hydrophobic surface. We found that strict rules govern the selection of alternative splice variants aimed to preserve the integrity of globular domains: alternative splice sites (i) tend to avoid globular domains or (ii) affect them only marginally or (iii) tend to coincide with a location where the exposed hydrophobic surface is minimal or (iv) the protein is disordered. We also observed an inverse correlation between the domain fraction lost and the full length of the minor isoform containing the domain, possibly indicating a buffering effect for the isoform protein counteracting the domain truncation effect. These observations provide the basis for a prediction method (currently under development) to predict the viability of splice variants

    DisProt: intrinsic protein disorder annotation in 2020

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    The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the ‘dark’ proteome

    Non-Linear Population Firing Rates and Voltage Sensitive Dye Signals in Visual Areas 17 and 18 to Short Duration Stimuli

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    Visual stimuli of short duration seem to persist longer after the stimulus offset than stimuli of longer duration. This visual persistence must have a physiological explanation. In ferrets exposed to stimuli of different durations we measured the relative changes in the membrane potentials with a voltage sensitive dye and the action potentials of populations of neurons in the upper layers of areas 17 and 18. For durations less than 100 ms, the timing and amplitude of the firing and membrane potentials showed several non-linear effects. The ON response became truncated, the OFF response progressively reduced, and the timing of the OFF responses progressively delayed the shorter the stimulus duration. The offset of the stimulus elicited a sudden and strong negativity in the time derivative of the dye signal. All these non-linearities could be explained by the stimulus offset inducing a sudden inhibition in layers II–III as indicated by the strongly negative time derivative of the dye signal. Despite the non-linear behavior of the layer II–III neurons the sum of the action potentials, integrated from the peak of the ON response to the peak of the OFF response, was almost linearly related to the stimulus duration

    Caractérisation des périodes de sécheresse sur le domaine de l'Afrique simulée par le Modèle Régional Canadien du Climat (MRCC5)

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    Les conséquences des changements climatiques sur la fréquence ainsi que sur l'intensité des précipitations auront un impact direct sur les périodes de sécheresse et par conséquent sur différents secteurs économiques tels que le secteur de l'agriculture. Ainsi, dans cette étude, l'habilité du Modèle Régional Canadien du Climat (MRCC5) à simuler les différentes caractéristiques des périodes de sécheresse est évaluée pour 4 seuils de précipitation soit 0.5 mm, 1 mm, 2 mm et 3 mm. Ces caractéristiques incluent le nombre de jours secs, le nombre de périodes de sécheresse ainsi que le maximum de jours consécutifs sans précipitation associé à une récurrence de 5 ans. Les résultats sont présentés pour des moyennes annuelles et saisonnières. L'erreur de performance est évaluée en comparant le MRCC5 piloté par ERA-Interim aux données d'analyses du GPCP pour le climat présent (1997-2008). L'erreur due aux conditions aux frontières c'est-à-dire les erreurs de pilotage du MRCC5, soit par CanESM2 et par ERA-Interim ainsi que l'évaluation de la valeur ajoutée du MRCC5 face au CanESM2 sont également analysées. L'analyse de ces caractéristiques est également faite dans un contexte de climat changeant pour deux périodes futures, soit 2041-2070 et 2071-2100 à l'aide du MRCC5 piloté par le modèle de circulation générale CanESM2 de même que par le modèle CanESM2 sous le scénario RCP 4.5. Les résultats suggèrent que le MRCC5 piloté par ERA-Interim a tendance à surestimer la moyenne annuelle du nombre de jours secs ainsi que le maximum de jours consécutifs sans précipitation associé à une récurrence de 5 ans dans la plupart des régions de l'Afrique et une tendance à sous-estimer le nombre de périodes de sécheresse. En général, l'erreur de performance est plus importante que l'erreur due aux conditions aux frontières pour les différentes caractéristiques de périodes de sécheresse. Pour les régions équatoriales, les changements appréhendés par le MRCC5 piloté par CanESM2 pour les différentes caractéristiques de périodes de sécheresse et pour deux périodes futures (2041-2070 et 2071-2100), suggèrent une augmentation significatives du nombre de jours secs ainsi que du maximum de jours consécutifs sans précipitation associé à une récurrence de 5 ans. Une diminution significative du nombre de périodes de sécheresse est aussi prévue.\ud ______________________________________________________________________________ \ud MOTS-CLÉS DE L’AUTEUR : Modèle Régional du Climat, Changement climatique, Jours secs, Nombre de périodes de sécheresse, Événement de faible récurrence, Afriqu

    Critical assessment of protein intrinsic disorder prediction

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    Abstract: Intrinsically disordered proteins, defying the traditional protein structure–function paradigm, are a challenge to study experimentally. Because a large part of our knowledge rests on computational predictions, it is crucial that their accuracy is high. The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in prediction of intrinsically disordered regions and the subset of residues involved in binding. A total of 43 methods were evaluated on a dataset of 646 proteins from DisProt. The best methods use deep learning techniques and notably outperform physicochemical methods. The top disorder predictor has Fmax = 0.483 on the full dataset and Fmax = 0.792 following filtering out of bona fide structured regions. Disordered binding regions remain hard to predict, with Fmax = 0.231. Interestingly, computing times among methods can vary by up to four orders of magnitude

    Modelling human choices: MADeM and decision‑making

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    Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

    Cocaine-Induced Changes in Low-Dimensional Attractors of Local Field Potentials in Optogenetic Mice

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    Optogenetically evoked local field potential (LFP) recorded from the medial prefrontal cortex (mPFC) of mice during basal conditions and following a systemic cocaine administration were analyzed. Blue light stimuli were delivered to mPFC through a fiber optic every 2 s and each trial was repeated 100 times. As in the previous study, we used a surrogate data method to check that nonlinearity was present in the experimental LFPs and only used the last 1.5 s of steady activity to measure the LFPs phase resetting induced by the brief 10 ms light stimulus. We found that the steady dynamics of the mPFC in response to light stimuli could be reconstructed in a three-dimensional phase space with topologically similar “8”-shaped attractors across different animals. Therefore, cocaine did not change the complexity of the recorded nonlinear data compared to the control case. The phase space of the reconstructed attractor is determined by the LFP time series and its temporally shifted versions by a multiple of some lag time. We also compared the change in the attractor shape between cocaine-injected and control using (1) dendrogram clustering and (2) Frechet distance. We found about 20% overlap between control and cocaine trials when classified using dendrogram method, which suggest that it may be possible to describe mathematically both data sets with the same model and slightly different model parameters. We also found that the lag times are about three times shorter for cocaine trials compared to control. As a result, although the phase space trajectories for control and cocaine may look similar, their dynamics is significantly different

    Dopamine receptor antagonists effects on low-dimensional attractors of local field potentials in optogenetic mice.

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    The goal of this study was to investigate the effects of acute cocaine injection or dopamine (DA) receptor antagonists on the medial prefrontal cortex (mPFC) gamma oscillations and their relationship to short term neuroadaptation that may mediate addiction. For this purpose, optogenetically evoked local field potentials (LFPs) in response to a brief 10 ms laser light pulse were recorded from 17 mice. D1-like receptor antagonist SCH 23390 or D2-like receptor antagonist sulpiride, or both, were administered either before or after cocaine. A Euclidian distance-based dendrogram classifier separated the 100 trials for each animal in disjoint clusters. When baseline and DA receptor antagonists trials were combined in a single trial, a minimum of 20% overlap occurred in some dendrogram clusters, which suggests a possible common, invariant, dynamic mechanism shared by both baseline and DA receptor antagonists data. The delay-embedding method of neural activity reconstruction was performed using the correlation time and mutual information to determine the lag/correlation time of LFPs and false nearest neighbors to determine the embedding dimension. We found that DA receptor antagonists applied before cocaine cancels out the effect of cocaine and leaves the lag time distributions at baseline values. On the other hand, cocaine applied after DA receptor antagonists shifts the lag time distributions to longer durations, i.e. increase the correlation time of LFPs. Fourier analysis showed that a reasonable accurate decomposition of the LFP data can be obtained with a relatively small (less than ten) Fourier coefficients
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