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Oliveira, R.

Publications and source records attributed to Oliveira, R..

25 records · Page 2Linked to original sources

A general deep hybrid model for bioreactor systems: combining first Principles equations with deep neural networks

Numerous studies have reported the use of hybrid semiparametric systems that combine shallow neural networks with mechanistic models for bioprocess modeling. Here we revisit the general bioreactor hybrid modeling problem and introduce some of the most recent deep learning techniques. The single layer networks were extended to multi-layer networks with varying depths and combined with First Principles equations in the form of deep hybrid models. Deep learning techniques, namely the adaptive moment estimation method (ADAM), stochastic regularization and depth-dependent weights initialization were evaluated. Modified sensitivity equations are proposed for the computation of gradients in order to reduce CPU time for the training of deep hybrid models. The methods are illustrated with applications to a synthetic dataset and a pilot 50 L MUT+ Pichia pastoris process expressing a single chain antibody fragment. All in all, the results point to a systematic generalization improvement of deep hybrid models over its shallow counterpart. Moreover, the CPU cost to train the deep hybrid models is shown to be lower than for the shallow counterpart. In the pilot 50L MUT+ Pichia pastoris data set, the prediction accuracy was increased by 18.4% and the CPU decreased by 43.4%. HighlightsO_LIShallow hybrid models have been widely used for bioprocess modeling and optimization C_LIO_LINon-deep training using e.g. the Levenberg - Marquardt method, cross-validation and indirect sensitivity equations have been the methods of choice C_LIO_LIDeep learning with ADAM, stochastic regularization and indirect sensitivity significantly reduces the training CPU C_LIO_LIThe generalization capacity of deep hybrid models systematically outperforms that of shallow hybrid models C_LI

systems biology↗

In-vivo estimation of axonal morphology from MRI and EEG data

PurposeWe present a novel approach that allows the estimation of morphological features of axonal fibers from data acquired in-vivo in humans. This approach allows the assessment of white matter microscopic properties non-invasively with improved specificity. TheoryThe proposed approach is based on a biophysical model of Magnetic Resonance Imaging (MRI) data and of axonal conduction velocity estimates obtained with Electroencephalography (EEG). In a white matter tract of interest, these data depend on 1) the distribution of axonal radius - P(r)- and 2) the g-ratio of the individual axons that compose this tract - g(r). P(r)is assumed to follow a Gamma distribution with mode and scale parameters, M and{theta} , and g(r) is described by a power-law with parameters and {beta}. MethodsMRI and EEG data were recorded from 14 healthy volunteers. MRI data were collected with a 3T scanner. MRI g-ratio maps were computed and sampled along the visual transcallosal tract. EEG data were recorded using a 128-lead system with a visual Poffenberg paradigm. The interhemispheric transfer time and axonal conduction velocity were computed from the EEG current density at the group level. Using the MRI and EEG measures and the proposed model, we estimated morphological properties of axons in the visual transcallosal tract. ResultsThe estimated interhemispheric transfer time was 11.72{+/-}2.87 ms, leading to an average conduction velocity across subjects of 13.22{+/-}1.18 m/s. Out of the 4 free parameters of the proposed model, we estimated{theta} - the width of the right tail of the axonal radius distribution and {beta} - the scaling factor of the axonal g-ratio, a measure of fiber myelination. Across subjects, the parameter{theta} was 0.40{+/-}0.07 {micro}m and the parameter {beta} was 0.67{+/-}0.02 {micro}m-. ConclusionsThe estimates of axonal radius and myelination are consistent with histological findings, illustrating the feasibility of this approach. The proposed method allows the measurement of the distribution of axonal radius and myelination within a white matter tract, opening new avenues for the combined study of brain structure and function, and for in-vivo histological studies of the human brain.

neuroscience↗

Social and asocial learning in zebrafish are encoded by a shared brain network that is differentially modulated by local activation

Group living animals can use social and asocial cues to predict the presence of a reward or a punishment in the environment through associative learning. The degree to which social and asocial learning share the same mechanisms is still a matter of debate, and, so far, studies investigating the neuronal basis of these two types of learning are scarce and have been restricted to primates, including humans, and rodents. Here we have used a Pavlovian fear conditioning paradigm in which a social (fish image) or an asocial (circle image) conditioned stimulus (CS) have been paired with an unconditioned stimulus (US=food), and we have used the expression of the immediate early gene c-fos to map the neural circuits associated with social and asocial learning. Our results show that the learning performance is similar with social (fish image) and asocial (circle image) CSs. However, the brain regions involved in each learning type are distinct. Social learning is associated with an increased expression of c-fos in olfactory bulbs, ventral zone of ventral telencephalic area, ventral habenula and ventromedial thalamus, whereas asocial learning is associated with a decreased expression of c-fos in dorsal habenula and anterior tubercular nucleus. Using egonetworks, we further show that each learning type has an associated pattern of functional connectivity across brain regions. Moreover, a community analysis of the network data reveals four segregated functional submodules, which seem to be associated with different cognitive functions involved in the learning tasks: a generalized attention module, a visual response module, a social stimulus integration module and a learning module. Together, these results suggest that, although there are localized differences in brain activity between social and asocial learning, the two learning types share a common learning module and social learning also recruits a specific social stimulus integration module. Therefore, our results support the occurrence of a common general-purpose learning module, that is differentially modulated by localized activation in social and asocial learning.

animal behavior and cognition↗

Oxytocin regulation of social transmission of fear in zebrafish reveals its evolutionary conserved role in emotional contagion

Emotional contagion is the most ancestral form of empathy that relies on simple perception-action mechanisms, on top of which more complex forms of empathic behaviors, such as consolation and helping, have evolved. Here we tested to what extent the proximate mechanisms of emotional contagion are evolutionary conserved by assessing the role of oxytocin, known to regulate empathic behaviors in mammals, in social fear contagion in zebrafish, which represents an evolutionary divergent line to that of tetrapods, within vertebrates. Using mutants for the ligand of the fish oxytocin nonapeptide and both of its receptors in zebrafish we showed that oxytocin is necessary for observer zebrafish to copy the distressed behavior of conspecific demonstrators. Exogeneous administration of oxytocin to the ligand mutant rescued the ability of observers to express social fear transmission, indicating that oxytocin is not only necessary but also sufficient for emotional contagion. The brain regions in the ventral telencephalon that are associated with emotional contagion in zebrafish are homologous to those known to be involved in the same process in rodents (e.g. striatum, lateral septum), and receive direct projections from oxytocinergic neurons located in the pre-optic area. Finally, we ruled out the hypothesis that social transmission of fear in zebrafish merely relies on behavior contagion by motor imitation, and we showed that it rather relies on emotion discrimination. Together our results support an evolutionary conserved role for oxytocin as a key regulator of basic empathic behaviors across vertebrates. One-Sentence SummaryOxytocin is necessary and sufficient for social fear contagion in zebrafish supporting an evolutionary conserved role for oxytocin in emotional contagion among vertebrates.

animal behavior and cognition↗

Reprogramming of Human Cells to Pluripotency Induces CENP-A Chromatin Depletion

Pluripotent stem cells (PSCs) are central to development as they are the precursors of all cell types in the embryo. Therefore, maintaining a stable karyotype is essential, both for their physiological role as well as for use in regenerative medicine. In culture, an estimated 10-30% of PSC lines present karyotypic abnormalities, but the underlying causes remain unknown. To gain insight into the mitotic capacity of human embryonic stem cells and induced pluripotent stem cells, we explore the structure of the centromere and kinetochore. Centromere function depends on CENP-A nucleosome-defined chromatin. We show that while PSCs maintain abundant pools of CENP-A, CENP-C and CENP-T, these essential centromere components are strongly reduced at stem cell centromeres. Outer kinetochore recruitment is also impaired to a lesser extent, indicating an overall weaker kinetochore. This impairment is specific for the kinetochore forming centromere complex while the inner centromere protein Aurora B remains unaffected. We further show that, similar to differentiated human cells, CENP-A chromatin assembly in PSCs requires transition into G1 phase. Finally, reprogramming experiments indicate that reduction of centromeric CENP-A levels is an early event during dedifferentiation, coinciding with global chromatin remodelling. Our characterisation of centromeres in human stem cells drives new hypotheses including a possible link between impaired centromere function and stem cell aneuploidies.

cell biology↗

Impeding transcription of expanded microsatellite repeats by deactivated Cas9

Transcription of expanded microsatellite repeats is associated with multiple human diseases, including myotonic dystrophy, Fuchs endothelial corneal dystrophy, and C9orf72-ALS/FTD. Eliminating or reducing production of RNA and proteins arising from these expanded loci holds therapeutic benefit. Here, we tested the hypothesis that a deactivated form of the Cas9 enzyme impedes transcription across expanded microsatellites. We observed a repeat length-, PAM-, and strand-dependent reduction in the abundance of repeat-containing RNAs upon targeting dCas9 directly to repeat sequences. Aberrant splicing patterns were rescued in DM1 cells, and production of RAN peptides characteristic of DM1, DM2, and C9orf72-ALS/FTD cells was drastically decreased. Systemic delivery of dCas9/gRNA by adeno-associated virus led to reductions in pathological RNA foci, rescue of chloride channel 1 protein expression, and decreased myotonia. These observations suggest that transcription of microsatellite repeat-containing RNAs is more sensitive to perturbation than transcription of other RNAs, indicating potentially viable strategies for therapeutic intervention.

molecular biology↗

Single-Trial Inhibition of Anterior Cingulate Disrupts Model-based Reinforcement Learning in a Two-step Decision Task.

The anterior cingulate cortex (ACC) is implicated in learning the value of actions, but it remains poorly understood whether and how it contributes to model-based mechanisms that use action-state predictions and afford behavioural flexibility. To isolate these mechanisms, we developed a multi-step decision task for mice in which both action-state transition probabilities and reward probabilities changed over time. Calcium imaging revealed ramps of choice-selective neuronal activity, followed by an evolving representation of the state reached and trial outcome, with different neuronal populations representing reward in different states. ACC neurons represented the current action-state transition structure, whether state transitions were expected or surprising, and the predicted state given chosen action. Optogenetic inhibition of ACC blocked the influence of action-state transitions on subsequent choice, without affecting the influence of rewards. These data support a role for ACC in model-based reinforcement learning, specifically in using action-state transitions to guide subsequent choice. HighlightsO_LIA novel two-step task disambiguates model-based and model-free RL in mice. C_LIO_LIACC represents all trial events, reward representation is contextualised by state. C_LIO_LIACC represents action-state transition structure, predicted states, and surprise. C_LIO_LIInhibiting ACC impedes action-state transitions from influencing subsequent choice. C_LI

neuroscience↗