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Biology subjects

Mayer, P.

Publications and source records attributed to Mayer, P..

4 recordsLinked to original sources

Surrogate Gradients for Gradient-Based Parameter Estimation in Simplified Neuron Models

Simplified spiking neuron models such as the Adaptive Exponential Integrate-and-Fire (AdEx) model reproduce the firing behaviour of diverse neuron types at a fraction of the cost of biophysically detailed models, making them attractive for large-scale brain simulation. Fitting their parameters to recordings, however, still relies on derivative-free search such as grid search or evolutionary algorithms, because the discrete spike-and-reset mechanism renders these models non-differentiable. Surrogate gradients, used in deep spiking networks, replace the spike derivative with a smooth approximation on the backward pass. Whether they also enable efficient gradient-based parameter estimation for single simplified neurons is untested. We implement a differentiable AdEx model with a surrogate-gradient variant in the Jaxley framework. The implementation is on par with target-compiled C++ Brian2 code while remaining end-to-end differentiable, vmap-batchable and GPU/TPU-portable. It is 200 times faster than Brian2's default runtime mode. Across a recovery-radius benchmark of 2,700 paired runs, gradient-based fitting never matched a gradient-free Nelder-Mead baseline. At sub- threshold levels, gradient descent instead beats Nelder-Mead. The obstacle is therefore the spike mechanism and the loss geometry it induces, not gradient descent itself.

bioinformatics↗

Conservation vs. Wild-Animal Suffering : how can population dynamics help ?

Conservation and ethical consideration for animal welfare in the wild appear to be synergetic because they both care for non-human animals. However, many practices such as culling seem to achieve conservation purposes but at the cost of producing a lot of wild-animal suffering, antagonizing conservationists and animal rights advocates. To explore this tension, we model the suffering of animals in wild ecosystems by resorting to classical population dynamics equations and using death rates as a metric of suffering. Our results show that, depending on the structure and parameters of the ecosystem, animal rights advocates and conservationists can have either opposing or compatible interests, where conserving species can go hand in hand with reducing the overall suffering. These models contribute to the concrete question of how to cope with suffering in the wild and may help ecosystem managers who are regularly confronted with interventions in the wild.

ecology↗

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2

A detailed understanding of antibody-based SARS-CoV-2 immunity has critical implications for overcoming the COVID-19 pandemic and for informing on vaccination strategies. In this study, we evaluated the dynamics of the SARS-CoV-2 antibody response in a cohort of 963 recovered individuals over a period of 10 months. Investigating a total of 2,146 samples, we detected an initial SARS-CoV-2 antibody response in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of recovered patients demonstrated exceptional SARS-CoV-2 neutralizing activity, defining them as elite neutralizers. These individuals also possessed effective cross-neutralizing IgG antibodies to SARS-CoV-1 without any known prior exposure to this virus. By applying multivariate statistical modeling, we found that sero-reactivity, age, time since disease onset, and fever are key factors predicting SARS-CoV-2 neutralizing activity in mild courses of COVID-19. Investigating longevity of the antibody response, we detected loss of anti-spike reactivity in 13% of individuals 10 months after infection. Moreover, neutralizing activity had an initial half-life of 6.7 weeks in serum versus 30.8 weeks in purified IgG samples indicating the presence of a more stable and long-term memory IgG B cell repertoire in the majority of individuals recovered from COVID-19. Our results demonstrate a broad spectrum of the initial SARS-CoV-2 neutralizing antibody response depending on clinical characteristics, with antibodies being maintained in the majority of individuals for the first 10 months after mild course of COVID-19.

immunology↗

Modelling bioactivities of combinations of whole extracts of edibles with a simplified theoretical framework reveals the statistical role of molecular diversity and system complexity in their mode of action and their nearly certain safety

Network pharmacology and polypharmacology are emerging as novel drug discovery paradigms. The many discovery, safety and regulatory issues they raise may become tractable with polypharmacological combinations of natural compounds found in whole extracts of edible and mixes thereof. The primary goal of this work is to get general insights underlying the innocuity and the emergence of beneficial and toxic activities of combinations of many compounds in general and of edibles in particular. A simplified model of compounds interactions with an organism and of their desired and undesired effects is constructed by considering the departure from equilibrium of interconnected biological features. This model allows to compute the scaling of the probability of significant effects relative to nutritional diversity, organism complexity and synergy resulting from mixing compounds and edibles. It allows also to characterize massive indirect perturbation mode of action drugs as a potential novel multi-compound-multi-target pharmaceutical class, coined Ediceuticals when based on edibles. Their mode of action may readily target differentially organisms system robustness as such based on differential complexity for discovering nearly certainly safe novel antimicrobials and anti-cancer treatments. This very general model provides also a theoretical framework to several pharmaceutical and nutritional observations. In particular, it characterizes two classes of undesirable effects of drugs, and may question the interpretation of undesirable effects in healthy subjects. It also formalizes nutritional diversity as such as a novel statistical supra-chemical parameter that may contribute to guide nutritional health intervention. Finally, it is to be noted that a similar formalism may be further applicable to model whole ecosystems in general.

pharmacology and toxicology↗