Successes and critical failures of neural networks in capturing human-like speech recognition

Natural and artificial audition can in principle evolve different solutions to a given problem. The constraints of the task, however, can nudge the cognitive science and engineering of audition to qualitatively converge, suggesting that a closer mutual examination would improve artificial hearing systems and process models of the mind and brain. Speech recognition - an area ripe for such exploration - is inherently robust in humans to a number transformations at various spectrotemporal granularities. To what extent are these robustness profiles accounted for by high-performing neural network systems? We bring together experiments in speech recognition under a single synthesis framework to evaluate state-of-the-art neural networks as stimulus-computable, optimized observers. In a series of experiments, we (1) clarify how influential speech manipulations in the literature relate to each other and to natural speech, (2) show the granularities at which machines exhibit out-of-distribution robustness, reproducing classical perceptual phenomena in humans, (3) identify the specific conditions where model predictions of human performance differ, and (4) demonstrate a crucial failure of all artificial systems to perceptually recover where humans do, suggesting a key specification for theory and model building. These findings encourage a tighter synergy between the cognitive science and engineering of audition

The piranha genome provides molecular insight associated to its unique feeding behavior

The piranha enjoys notoriety due to its infamous predatory behavior but much is still not understood about its evolutionary origins and the underlying molecular mechanisms for its unusual feeding biology. We sequenced and assembled the red-bellied piranha (Pygocentrus nattereri) genome to aid future phenotypic and genetic investigations. The assembled draft genome is similar to other related fishes in repeat composition and gene count. Our evaluation of genes under positive selection suggests candidates for adaptations of piranhas’ feeding behavior in neural functions, behavior, and regulation of energy metabolism. In the fasted brain, we find genes differentially expressed that are involved in lipid metabolism and appetite regulation as well as genes that may control the aggression/boldness behavior of hungry piranhas. Our first analysis of the piranha genome offers new insight and resources for the study of piranha biology and for feeding motivation and starvation in other organisms

A comparative view on sex differentiation and gametogenesis genes in lungfish and coelacanths

none8siGonadal sex differentiation andreproductionare the keys totheperpetuationof favorable gene combinations andpositively selected traits. In vertebrates, several gonad development features that differentiate tetrapods and fishes are likely to be, at least in part, related to the water-to-land transition. The collection of information from basal sarcopterygians, coelacanths, and lungfishes, is crucial to improve our understanding of the molecular evolution of pathways involved in reproductive functions, since these organisms are generally regarded as “living fossils” and as the direct ancestors of tetrapods. Here, we report for the first time the characterization of >50 genes related to sex differentiation and gametogenesis in Latimeria menadoensis and Protopterus annectens. Although the expression profiles of most genes is consistent with the intermediate position of basal sarcopterygians between actinopterygian fish and tetrapods, their phylogenetic placement and presence/absence patterns often reveal a closer affinity to the tetrapod orthologs. On the other hand, particular genes, for example, the male gonad factor gsdf (Gonadal Soma-Derived Factor), provide examples of ancestral traits sharedwith actinopterygians,which disappeared in the tetrapod lineage.openMaria Assunta Biscotti, Mateus Contar Adolfi, Marco Barucca, Mariko Forconi, Alberto Pallavicini, Marco Gerdol, Adriana Canapa, Manfred SchartlBiscotti, Maria Assunta; Contar Adolfi, Mateus; Barucca, Marco; Forconi, Mariko'; Pallavicini, Alberto; Gerdol, Marco; Canapa, Adriana; Schartl, Manfre

Site-Directed φC31-Mediated Integration and Cassette Exchange in Anopheles Vectors of Malaria

Functional genomic analysis and related strategies for genetic control of malaria rely on validated and reproducible methods to accurately modify the genome of Anopheles mosquitoes. Amongst these methods, the φC31 system allows precise and stable site-directed integration of transgenes, or the substitution of integrated transgenic cassettes via recombinase-mediated cassette exchange (RMCE). This method relies on the action of the Streptomyces φC31 bacteriophage integrase to catalyze recombination between two specific attachment sites designated attP (derived from the phage) and attB (derived from the host bacterium). The system uses one or two attP sites that have been integrated previously into the mosquito genome and attB site(s) in the donor template DNA. Here we illustrate how to stably modify the genome of attP-bearing Anopheles docking lines using two plasmids: an attB-tagged donor carrying the integration or exchange template and a helper plasmid encoding the φC31 integrase. We report two representative results of φC31mediated site-directed modification: the single integration of a transgenic cassette in An. stephensi and RMCE in An. gambiae mosquitoes. φC31-mediated genome manipulation offers the advantage of reproducible transgene expression from validated, fitness neutral genomic sites, allowing comparative qualitative and quantitative analyses of phenotypes. The site-directed nature of the integration also substantially simplifies the validation of the single insertion site and the mating scheme to obtain a stable transgenic line. These and other characteristics make the φC31 system an essential component of the genetic toolkit for the transgenic manipulation of malaria mosquitoes and other insect vectors

New insecticide screening platforms indicate that Mitochondrial Complex I inhibitors are susceptible to cross-resistance by mosquito P450s that metabolise pyrethroids

Fenazaquin, pyridaben, tolfenpyrad and fenpyroximate are Complex I inhibitors offering a new mode of action for insecticidal malaria vector control. However, extended exposure to pyrethroid based products such as long-lasting insecticidal nets (LLINs) has created mosquito populations that are largely pyrethroid-resistant, often with elevated levels of P450s that can metabolise and neutralise diverse substrates. To assess cross-resistance liabilities of the Complex I inhibitors, we profiled their susceptibility to metabolism by P450s associated with pyrethroid resistance in Anopheles gambiae (CYPs 6M2, 6P3, 6P4, 6P5, 9J5, 9K1, 6Z2) and An. funestus (CYP6P9a). All compounds were highly susceptible. Transgenic An. gambiae overexpressing CYP6M2 or CYP6P3 showed reduced mortality when exposed to fenpyroximate and tolfenpyrad. Mortality from fenpyroximate was also reduced in pyrethroid-resistant strains of An. gambiae (VK7 2014 and Tiassalé 13) and An. funestus (FUMOZ-R). P450 inhibitor piperonyl butoxide (PBO) significantly enhanced the efficacy of fenpyroximate and tolfenpyrad, fully restoring mortality in fenpyroximate-exposed FUMOZ-R. Overall, results suggest that in vivo and in vitro assays are a useful guide in the development of new vector control products, and that the Complex I inhibitors tested are susceptible to metabolic cross-resistance and may lack efficacy in controlling pyrethroid resistant mosquitoes

Gibbs sampling with people

A core problem in cognitive science and machine learning is to understand how humans derive semantic representations from perceptual objects, such as color from an apple, pleasantness from a musical chord, or seriousness from a face. Markov Chain Monte Carlo with People (MCMCP) is a prominent method for studying such representations, in which participants are presented with binary choice trials constructed such that the decisions follow a Markov Chain Monte Carlo acceptance rule. However, while MCMCP has strong asymptotic properties, its binary choice paradigm generates relatively little information per trial, and its local proposal function makes it slow to explore the parameter space and find the modes of the distribution. Here we therefore generalize MCMCP to a continuous-sampling paradigm, where in each iteration the participant uses a slider to continuously manipulate a single stimulus dimension to optimize a given criterion such as 'pleasantness'. We formulate both methods from a utility-theory perspective, and show that the new method can be interpreted as 'Gibbs Sampling with People' (GSP). Further, we introduce an aggregation parameter to the transition step, and show that this parameter can be manipulated to flexibly shift between Gibbs sampling and deterministic optimization. In an initial study, we show GSP clearly outperforming MCMCP; we then show that GSP provides novel and interpretable results in three other domains, namely musical chords, vocal emotions, and faces. We validate these results through large-scale perceptual rating experiments. The final experiments use GSP to navigate the latent space of a state-of-the-art image synthesis network (StyleGAN), a promising approach for applying GSP to high-dimensional perceptual spaces. We conclude by discussing future cognitive applications and ethical implications

Gibbs sampling with people

A core problem in cognitive science and machine learning is to understand how humans derive semantic representations from perceptual objects, such as color from an apple, pleasantness from a musical chord, or seriousness from a face. Markov Chain Monte Carlo with People (MCMCP) is a prominent method for studying such representations, in which participants are presented with binary choice trials constructed such that the decisions follow a Markov Chain Monte Carlo acceptance rule. However, while MCMCP has strong asymptotic properties, its binary choice paradigm generates relatively little information per trial, and its local proposal function makes it slow to explore the parameter space and find the modes of the distribution. Here we therefore generalize MCMCP to a continuous-sampling paradigm, where in each iteration the participant uses a slider to continuously manipulate a single stimulus dimension to optimize a given criterion such as 'pleasantness'. We formulate both methods from a utility-theory perspective, and show that the new method can be interpreted as 'Gibbs Sampling with People' (GSP). Further, we introduce an aggregation parameter to the transition step, and show that this parameter can be manipulated to flexibly shift between Gibbs sampling and deterministic optimization. In an initial study, we show GSP clearly outperforming MCMCP; we then show that GSP provides novel and interpretable results in three other domains, namely musical chords, vocal emotions, and faces. We validate these results through large-scale perceptual rating experiments. The final experiments use GSP to navigate the latent space of a state-of-the-art image synthesis network (StyleGAN), a promising approach for applying GSP to high-dimensional perceptual spaces. We conclude by discussing future cognitive applications and ethical implications

Functional genetic validation of key genes conferring insecticide resistance in the major African malaria vector

Resistance in to members of all 4 major classes (pyrethroids, carbamates, organochlorines, and organophosphates) of public health insecticides limits effective control of malaria transmission in Africa. Increase in expression of detoxifying enzymes has been associated with insecticide resistance, but their direct functional validation in is still lacking. Here, we perform transgenic analysis using the GAL4/UAS system to examine insecticide resistance phenotypes conferred by increased expression of the 3 genes-, , and -most often found up-regulated in resistant We report evidence in that organophosphate and organochlorine resistance is conferred by overexpression of GSTE2 in a broad tissue profile. Pyrethroid and carbamate resistance is bestowed by similar overexpression, and confers only pyrethroid resistance when overexpressed in the same tissues. Conversely, such overexpression increases susceptibility to the organophosphate malathion, presumably due to conversion to the more toxic metabolite, malaoxon. No resistant phenotypes are conferred when either gene overexpression is restricted to the midgut or oenocytes, indicating that neither tissue is involved in insecticide resistance mediated by the candidate P450s examined. Validation of genes conferring resistance provides markers to guide control strategies, and the observed negative cross-resistance due to gives credence to proposed dual-insecticide strategies to overcome pyrethroid resistance. These transgenic -resistant lines are being used to test the "resistance-breaking" efficacy of active compounds early in their development