The genome of the venomous snail Lautoconus ventricosus shed light on the origin of conotoxin diversity

Background: Venoms are deadly weapons to subdue prey or deter predators that have evolved independently in many animal lineages. The genomes of venomous animals are essential to understand the evolutionary mechanisms involved in the origin and diversification of venoms. Results: Here, we report the chromosome-level genome of the venomous Mediterranean cone snail, Lautoconus ventricosus (Caenogastropoda: Conidae). The total size of the assembly is 3.59 Gb; it has high contiguity (N50 = 93.53 Mb) and 86.6 Mb of the genome assembled into the 35 largest scaffolds or pseudochromosomes. On the basis of venom gland transcriptomes, we annotated 262 complete genes encoding conotoxin precursors, hormones, and other venom-related proteins. These genes were scattered in the different pseudochromosomes and located within repetitive regions. The genes encoding conotoxin precursors were normally structured into 3 exons, which did not necessarily coincide with the 3 structural domains of the corresponding proteins. Additionally, we found evidence in the L. ventricosus genome for a past whole-genome duplication event by means of conserved gene synteny with the Pomacea canaliculata genome, the only one available at the chromosome level within Caenogastropoda. The whole-genome duplication event was further confirmed by the presence of a duplicated hox gene cluster. Key genes for gastropod biology including those encoding proteins related to development, shell formation, and sex were located in the genome. Conclusions: The new high-quality L. ventricosus genome should become a reference for assembling and analyzing new gastropod genomes and will contribute to future evolutionary genomic studies among venomous animals.This work was funded by the Spanish Ministry of Science and Innovation (CGL2016-75255-C2-1-P [AEI/FEDER, UE] and PID2019-103947GB-C22/AEI/10.13039/501100011033 to R.Z.; BES-2017-081195 to J.R.P.-B.; BES-2014-069575 to S.A.; IJCI-2016-29566 to I.I.). I.I. acknowledges the support from the European Research Council during the latest stages of the project (Grant Agreement No. 852725; ERC-StG "TerreStriAL" to Jan de Vries, University of Goettingen)

Reconfiguring the reader : convergence and participation in modern young adult fantasy fiction

PhD ThesisThis thesis explores digital-age literary and reading practices as they were influenced by participatory culture at the turn of the century. Participatory culture is analysed here through the work of Henry Jenkins, Hans Heino Ewers, Margaret Mackey and Katy Varnelis and is recognised as one in which individuals are socially connected to each other in an environment that offers support for creating and sharing interpretations and original works. It has relatively low barriers to artistic expression and civic participation, and fosters the sense of community growing around people’s common interests and ideologies, as expressed through performative manifestations such as gaming and fandom. Because juvenile fantasy fiction generally, and J. K. Rowling’s Harry Potter series (1997-2007) specifically, were at the centre of significant developments in response to participatory culture, Rowling’s books are used as a case study on the basis of which changing practices of reading, writing and interpretation of story, principally by children and young people, are mapped and appraised. One aim of this thesis is to evaluate how far participatory culture has affected what it means to be a reader of a text that exists in multiple formats: how each version of the text constructs and addresses its readers/viewers/players/co-creators, and the dynamics and interdependence between the different versions. A second but related aim is to test the claims of new media theorists, including Janet Murray, Pierre Lévy and Marie-Laure Ryan, among others, to establish how far texts, readers and the processes of reading have in fact changed. Specifically, it looks at how far the promises of reader participation and co-creation have been fulfilled, especially within the genre of children’s literature

Gas channel rerouting in a primordial enzyme: Structural insights of the carbon-monoxide dehydrogenase/acetyl-CoA synthase complex from the acetogen Clostridium autoethanogenum

Clostridium autoethanogenum, the bacterial model for biological conversion of waste gases into biofuels, grows under extreme carbon-monoxide (CO) concentrations. The strictly anaerobic bacterium derives its entire cellular energy and carbon from this poisonous gas, therefore requiring efficient molecular machineries for CO-conversion. Here, we structurally and biochemically characterized the key enzyme of the CO-converting metabolism: the CO-dehydrogenase/Acetyl-CoA synthase (CODH/ACS). We obtained crystal structures of natively isolated complexes from fructose-grown and CO-grown C. autoethanogenum cultures. Both contain the same isoforms and if the overall structure adopts the classic alpha(2)beta(2) architecture, comparable to the model enzyme from Moorella thermoacetica, the ACS binds a different position on the CODH core. The structural characterization of a proteolyzed complex and the conservation of the binding interface in close homologs rejected the possibility of a crystallization artefact. Therefore, the internal CO-channeling system, critical to transfer CO generated at the C-cluster to the ACS active site, drastically differs in the complex from C. autoethanogenum. The 1.9-angstrom structure of the CODH alone provides an accurate picture of the new CO-routes, leading to the ACS core and reaching the surface. Increased gas accessibility would allow the simultaneous CO-oxidation and acetyl-CoA production. Biochemical experiments showed higher flexibility of the ACS subunit from C. autoethanogenum compared to M. thermoacetica, albeit monitoring similar CO-oxidation and formation rates. These results show a reshuffling of internal CO-tunnels during evolution of these Firmicutes, putatively leading to a bidirectional complex that ensure a high flux of CO-conversion toward energy conservation, acting as the main cellular powerplant

Local farmer knowledge of adaptive management on diversified vegetable and berry farms in the northeastern US

Agricultural adaptation to climate change is notoriously context specific. Recently updated projections for the Northeastern US forecast increasingly severe and erratic precipitation events which pose significant risks to every sector of agricultural production in the region. Vegetable and berry farmers are among the most vulnerable to the risks of severe precipitation and drought due to the intensive soil and crop management strategies which characterize of this kind of production. To successfully adapt to a changing climate, these farmers need information which is tailored for the unique challenges of vegetable and berry production, framed at the level of climate impacts, and delivered through the familiar lexicon used by farmers in the region. My approach is grounded by partnerships with farmer networks to inform both the relevance of this information and my outreach strategy for sharing results. This research presents complimentary quantitative and qualitative data sets on adaptive management, and highlights the insight of farmers voices on innovative and promising solutions for managing climate related risks. The goal of the project was to create usable information for producers through a Farmer First approach which privileges the voices and experiences of farmers in determining the information and resources they need. As part of a broader project, this thesis analyzed the results of a regional survey of vegetable and berry growers conducted over the winter months of 2017-2018. The first chapter reviews theoretical foundations for academic study of agricultural management and climate change, with a focus on information usability. The second chapter applies theories of adaptation and resilience to identify agroecological principles for adapting farm management to water extremes and innovative practices emerging in the region. The third chapter uses a regression modelling approach to explore how adaptive management practices vary across site specific characteristics. Our analysis identifies trends and principles for adapting to water excess and water deficits on diversified vegetable and berry farms in the Northeast. The research findings highlight how site characteristics influence the selection of adaptive management practices on farms in the Northeast

Automated Deduction – CADE 28

This open access book constitutes the proceeding of the 28th International Conference on Automated Deduction, CADE 28, held virtually in July 2021. The 29 full papers and 7 system descriptions presented together with 2 invited papers were carefully reviewed and selected from 76 submissions. CADE is the major forum for the presentation of research in all aspects of automated deduction, including foundations, applications, implementations, and practical experience. The papers are organized in the following topics: Logical foundations; theory and principles; implementation and application; ATP and AI; and system descriptions

Rare-Event Estimation and Calibration for Large-Scale Stochastic Simulation Models

Stochastic simulation has been widely applied in many domains. More recently, however, the rapid surge of sophisticated problems such as safety evaluation of intelligent systems has posed various challenges to conventional statistical methods. Motivated by these challenges, in this thesis, we develop novel methodologies with theoretical guarantees and numerical applications to tackle them from different perspectives. In particular, our works can be categorized into two areas: (1) rare-event estimation (Chapters 2 to 5) where we develop approaches to estimating the probabilities of rare events via simulation; (2) model calibration (Chapters 6 and 7) where we aim at calibrating the simulation model so that it is close to reality. In Chapter 2, we study rare-event simulation for a class of problems where the target hitting sets of interest are defined via modern machine learning tools such as neural networks and random forests. We investigate an importance sampling scheme that integrates the dominating point machinery in large deviations and sequential mixed integer programming to locate the underlying dominating points. We provide efficiency guarantees and numerical demonstration of our approach. In Chapter 3, we propose a new efficiency criterion for importance sampling, which we call probabilistic efficiency. Conventionally, an estimator is regarded as efficient if its relative error is sufficiently controlled. It is widely known that when a rare-event set contains multiple "important regions" encoded by the dominating points, importance sampling needs to account for all of them via mixing to achieve efficiency. We argue that the traditional analysis recipe could suffer from intrinsic looseness by using relative error as an efficiency criterion. Thus, we propose the new efficiency notion to tighten this gap. In particular, we show that under the standard Gartner-Ellis large deviations regime, an importance sampling that uses only the most significant dominating points is sufficient to attain this efficiency notion. In Chapter 4, we consider the estimation of rare-event probabilities using sample proportions output by crude Monte Carlo. Due to the recent surge of sophisticated rare-event problems, efficiency-guaranteed variance reduction may face implementation challenges, which motivate one to look at naive estimators. In this chapter we construct confidence intervals for the target probability using this naive estimator from various techniques, and then analyze their validity as well as tightness respectively quantified by the coverage probability and relative half-width. In Chapter 5, we propose the use of extreme value analysis, in particular the peak-over-threshold method which is popularly employed for extremal estimation of real datasets, in the simulation setting. More specifically, we view crude Monte Carlo samples as data to fit on a generalized Pareto distribution. We test this idea on several numerical examples. The results show that in the absence of efficient variance reduction schemes, it appears to offer potential benefits to enhance crude Monte Carlo estimates. In Chapter 6, we investigate a framework to develop calibration schemes in parametric settings, which satisfies rigorous frequentist statistical guarantees via a basic notion that we call eligibility set designed to bypass non-identifiability via a set-based estimation. We investigate a feature extraction-then-aggregation approach to construct these sets that target at multivariate outputs. We demonstrate our methodology on several numerical examples, including an application to calibration of a limit order book market simulator. In Chapter 7, we study a methodology to tackle the NASA Langley Uncertainty Quantification Challenge, a model calibration problem under both aleatory and epistemic uncertainties. Our methodology is based on an integration of distributionally robust optimization and importance sampling. The main computation machinery in this integrated methodology amounts to solving sampled linear programs. We present theoretical statistical guarantees of our approach via connections to nonparametric hypothesis testing, and numerical performances including parameter calibration and downstream decision and risk evaluation tasks

Third Conference on Artificial Intelligence for Space Applications, part 1

The application of artificial intelligence to spacecraft and aerospace systems is discussed. Expert systems, robotics, space station automation, fault diagnostics, parallel processing, knowledge representation, scheduling, man-machine interfaces and neural nets are among the topics discussed

Investigating the functional and evolutionary significance of Group B Sox genes in arthropods

Group B Sox genes play a critical developmental role in both vertebrates and insects. Within the model species Drosophila melanogaster, two SoxB genes, Dichaete and SoxNeuro, have been shown to act as ‘master regulators’ in the early development of the central nervous system. SoxB genes have only been characterised in a handful of arthropod species thus far, with most work to date focusing on drosophilids. The purpose of this investigation was twofold. First, I set out to resolve the phylogenetic origins of arthropod SoxB genes, as mutually exclusive models explaining their emergence are still contested. I have identified and annotated the SoxB of several invertebrate taxa. In total, my investigation includes 24 different metazoan taxa, and represents the largest investigation of arthropod SoxB phylogeny to date. In light of this research, I have proposed a new model of SoxB evolution which resolves the conflicting elements of the two primary competing models. Second, to study the evolution of SoxB in terms of functional conservation/divergence, I selected the emerging model organism Tribolium castaneum to draw a comparative analysis with Drosophila melanogaster. I first began by characterising the spatiotemporal expression patterns of SoxNeuro mRNA in early Tribolium embryos using whole mount in situ hybridisation, and examined published Dichaete expression patterns in the context of central nervous system development in T. castaneum. Using these data, I draw a comparison to the expression profiles of Dichaete and SoxNeuro orthologues in Drosophila melanogaster and other species. I have found that both Dichaete and SoxNeuro expression patterns in the developing central nervous system are remarkably well-conserved across species. I also attempted to characterise genome-wide binding for both Dichaete and SoxNeuro proteins in Tribolium in what would have represented the first genomic investigation of its kind in this emerging species. Using a tethered DNA adenine methyltransferase (Dam) enzyme for both SoxNeuro and Dichaete, I hoped to characterise the genomic loci with which each protein interacts within the beetle genome (a technique known as DamID). Unfortunately, these last set of experiments have proved unsuccessful, despite several attempts which have made use of different promoters, different DNA enrichment methodologies, and tackling unforeseen DNA contamination issues. Nevertheless, the troubleshooting experiments that I have carried out will pave the way for further genomic experiments in Tribolium, easing the establishment of genomic research in this emerging organism.Medical Research Counci

Co-Speech Gesture in Communication and Cognition

xv, 256 p. : ill.This dissertation stages a reciprocal critique between traditional and marginal philosophical approaches to language on the one hand and interdisciplinary studies of speech-accompanying hand gestures on the other. Gesturing with the hands while speaking is a ubiquitous, cross-cultural human practice. Yet this practice is complex, varied, conventional, nonconventional, and above all under-theorized. In light of the theoretical and empirical treatments of language and gesture that I engage in, I argue that the hand gestures that spontaneously accompany speech are a part of language; more specifically, they are enactments of linguistic meaning. They are simultaneously (acts of) cognition and communication. Human communication and cognition are what they are in part because of this practice of gesturing. This argument has profound implications for philosophy, for gesture studies, and for interdisciplinary work to come. As further, strong proof of the pervasively embodied way that humans make meaning in language, reflection on gestural phenomena calls for a complete re-orientation in traditional analytic philosophy of language. Yet philosophical awareness of intersubjectivity and normativity as conditions of meaning achievement is well-deployed in elaborating and refining the minimal theoretical apparatus of present-day gesture studies. Triangulating between the most social, communicative philosophies of meaning and the most nuanced, reflective treatments of co-speech hand gesture, I articulate a new construal of language as embodied, world-embedded, intersubjectively normative, dynamic, multi-modal enacting of appropriative disclosure. Spontaneous co-speech gestures, while being indeed spontaneous, are nonetheless informed in various ways by conventions that they appropriate and deploy. Through this appropriation and deployment speakers enact, rather than represent, meaning, and they do so in various linguistic modalities. Seen thusly, gestures provide philosophers with a unique new perspective on the paradoxical determined-yet-free nature of all human meaning.Committee in charge: Mark Johnson, Chairperson; Ted Toadvine, Member; Naomi Zack, Member; Eric Pederson, Outside Membe

Computer Aided Verification

This open access two-volume set LNCS 10980 and 10981 constitutes the refereed proceedings of the 30th International Conference on Computer Aided Verification, CAV 2018, held in Oxford, UK, in July 2018. The 52 full and 13 tool papers presented together with 3 invited papers and 2 tutorials were carefully reviewed and selected from 215 submissions. The papers cover a wide range of topics and techniques, from algorithmic and logical foundations of verification to practical applications in distributed, networked, cyber-physical, and autonomous systems. They are organized in topical sections on model checking, program analysis using polyhedra, synthesis, learning, runtime verification, hybrid and timed systems, tools, probabilistic systems, static analysis, theory and security, SAT, SMT and decisions procedures, concurrency, and CPS, hardware, industrial applications