A Biologically Informed Hylomorphism

Although contemporary metaphysics has recently undergone a neo-Aristotelian revival wherein dispositions, or capacities are now commonplace in empirically grounded ontologies, being routinely utilised in theories of causality and modality, a central Aristotelian concept has yet to be given serious attention – the doctrine of hylomorphism. The reason for this is clear: while the Aristotelian ontological distinction between actuality and potentiality has proven to be a fruitful conceptual framework with which to model the operation of the natural world, the distinction between form and matter has yet to similarly earn its keep. In this chapter, I offer a first step toward showing that the hylomorphic framework is up to that task. To do so, I return to the birthplace of that doctrine - the biological realm. Utilising recent advances in developmental biology, I argue that the hylomorphic framework is an empirically adequate and conceptually rich explanatory schema with which to model the nature of organism

Linking working memory and long-term memory: A computational model of the learning of new words

The nonword repetition (NWR) test has been shown to be a good predictor of children’s vocabulary size. NWR performance has been explained using phonological working memory, which is seen as a critical component in the learning of new words. However, no detailed specification of the link between phonological working memory and long-term memory (LTM) has been proposed. In this paper, we present a computational model of children’s vocabulary acquisition (EPAM-VOC) that specifies how phonological working memory and LTM interact. The model learns phoneme sequences, which are stored in LTM and mediate how much information can be held in working memory. The model’s behaviour is compared with that of children in a new study of NWR, conducted in order to ensure the same nonword stimuli and methodology across ages. EPAM-VOC shows a pattern of results similar to that of children: performance is better for shorter nonwords and for wordlike nonwords, and performance improves with age. EPAM-VOC also simulates the superior performance for single consonant nonwords over clustered consonant nonwords found in previous NWR studies. EPAM-VOC provides a simple and elegant computational account of some of the key processes involved in the learning of new words: it specifies how phonological working memory and LTM interact; makes testable predictions; and suggests that developmental changes in NWR performance may reflect differences in the amount of information that has been encoded in LTM rather than developmental changes in working memory capacity. Keywords: EPAM, working memory, long-term memory, nonword repetition, vocabulary acquisition, developmental change

Bootstrapping Real-world Deployment of Future Internet Architectures

The past decade has seen many proposals for future Internet architectures. Most of these proposals require substantial changes to the current networking infrastructure and end-user devices, resulting in a failure to move from theory to real-world deployment. This paper describes one possible strategy for bootstrapping the initial deployment of future Internet architectures by focusing on providing high availability as an incentive for early adopters. Through large-scale simulation and real-world implementation, we show that with only a small number of adopting ISPs, customers can obtain high availability guarantees. We discuss design, implementation, and evaluation of an availability device that allows customers to bridge into the future Internet architecture without modifications to their existing infrastructure

Creating an Objective Methodology for Human-Robot Team Configuration Selection

As technology has been advancing and designers have been looking to future applications, it has become increasingly evident that robotic technology can be used to supplement, augment, and improve human performance of tasks. Team members can be combined in various combinations to better utilize their capabilities and skills to create more efficient and diversified operational teams. A primary obstacle to integrating new robotic technology has been the inability to quantitatively compare overall team performance between very different team configurations without limiting the analysis to a few metrics. To-date, mission designers have arbitrarily assigned importance to mission parameters, subjectively limiting the search space. While this has been effective at evaluating individual mission plans, the arbitrary evaluation criteria has made a straightforward comparison between different research projects and ranking scales impossible. The question then becomes how to select an objective set of criteria for any given problem. It is this final question that this research sought to answer. A methodology was developed to facilitate performance comparison amongst heterogeneous human and robot teams. This methodology makes no assumptions about mission priorities or preferences. Instead, it provides an objective, generic, quantitative method to reduce the complexity of the mission designer's decision space. It employs an heuristic, greedy objective reduction algorithm to reduce problem complexity and a multi-objective genetic algorithm to explore the design space. The human-robot team configuration selection problem was utilized as the application that motivated this research. The methodology, however, will be applicable to a wider domain of research. It will provide a structure to enable broader search of the design space, exploration of the differences between performance metrics, and comparison of optimization models that facilitate evaluation of the design options

sciCSR infers B cell state transition and predicts class-switch recombination dynamics using single-cell transcriptomic data

Class-switch recombination (CSR) is an integral part of B cell maturation. Here we present sciCSR (pronounced 'scissor', single-cell inference of class-switch recombination), a computational pipeline that analyzes CSR events and dynamics of B cells from single-cell RNA sequencing (scRNA-seq) experiments. Validated on both simulated and real data, sciCSR re-analyzes scRNA-seq alignments to differentiate productive heavy-chain immunoglobulin transcripts from germline 'sterile' transcripts. From a snapshot of B cell scRNA-seq data, a Markov state model is built to infer the dynamics and direction of CSR. Applying sciCSR on severe acute respiratory syndrome coronavirus 2 vaccination time-course scRNA-seq data, we observe that sciCSR predicts, using data from an earlier time point in the collected time-course, the isotype distribution of B cell receptor repertoires of subsequent time points with high accuracy (cosine similarity ~0.9). Using processes specific to B cells, sciCSR identifies transitions that are often missed by conventional RNA velocity analyses and can reveal insights into the dynamics of B cell CSR during immune response

Innate Immune Responses to Plasmodium Parasites

Bisher gibt es keine effektive Impfung gegen Malaria und der beste immunologische Schutz wird durch wiederholte intravenöse Injektion von nicht-vermehrungsfähigen Sporozoiten erreicht. Im Gegensatz dazu bietet die Infektion im Blutstadium nur eine Teilimmunität gegen schwere Verläufe der Krankheit. Um beide Prozesse besser zu verstehen, ist eine tiefgehende Untersuchung der Reaktion des angeborenen Immunsystems auf Sporozoiten, sowie Parasiten im Blutstadium erforderlich. Erkenntnisse hieraus können dabei helfen, die Überlegenheit des Sporozoiten-Impfstoffs zu verstehen und, letztendlich, seine Wirksamkeit in einem sichereren, kostengünstigeren und skalierbaren Impfstoff zu rekapitulieren. Um sterile Sporozoiten aus Mückenprärationen für in-vitro experimente zu gewinnen, wurden die Parasiten FACS sortiert und anschließend mit Makrophagen co-kultivert. RNA Sequenzierung der Makrophagen, zeigte ein von Sporozoiten induziertes Expressionsprofil, das durch die Expression von inflammatorischen Genen gekennzeichnet ist. Insbesondere CD201 wurde auf Makrophagen stark hochreguliert und könnte eine Rolle bei der gamma-delta T-Zell-Aktivierung spielen. Darüber hinaus kann gezeigt werden, dass die Aktivierung von Makrophagen durch Sporozoiten teilweise von TLR2 und MyD88 abhängig ist. Interessanterweise waren die genetischen Signaturen „Reaktion auf Verwundung" und „Makroautophagie" in Makrophagen überrepräsentiert die mit Sporozoiten co-kultiviert wurden und sind wahrscheinlich Folgen von aktiver Sporozoiten-Traversierung durch Makrophagen. In der Tat zeigten Mäuse, die mit Traversierungs-defizienten Sporozoiten geimpft wurden stark reduzierte CD8 T-Zell Antworten. Dies deutet auf eine mögliche Rolle der Zelltraversion bei der Induktion effektiver adaptiver Immunantworten hin. Insgesamt tragen diese Ergebnisse zu dem Verständnis der angeborenen Immunantwort auf Plasmodium-Parasiten bei und bieten weitere Möglichkeiten zur zukünftigen Forschung.Effective vaccination against malaria remains a critical element in the effort to eradicate the disease. So far, best protection is induced by repeated intravenous injection of irradiated, non-replicating sporozoites. In contrast, blood stage infection only affords semi-immunity after several disease episodes are endured. Therefore, in-depth analyses of innate immune responses to sporozoite and blood stage parasites are needed to understand the superiority of the attenuated sporozoite vaccine and ultimately, to recapitulate its efficacy in a safer, cheaper and more practical vaccine. To probe sporozoite-induced innate cell activation, parasites were flow sorted from salivary gland extracts. In a reductionist system, sorted P. berghei sporozoites were co-cultured with primary mouse macrophages. Transcriptomic analysis of sporozoite-experienced macrophages revealed a distinct expression profile characterized by NF-κB driven expression of inflammatory mediators. In particular, CD201, a CD1d-like transmembrane receptor with lipid presentation capabilities, was strongly upregulated on macrophages and might play a role in gamma-delta T-cell activation. In addition, first evidence is provided that macrophage activation by sporozoites is partly dependent on TLR2 and MyD88. Intriguingly, ‘response to wounding’ and ‘macroautophagy’ signatures were enriched in sporozoite-stimulated macrophages and are likely consequences of active sporozoite traversal through innate cells. Indeed, in vivo vaccination with spect1 knockout sporozoites, which are deficient in cell traversal, induced a defective CD8 T-cell response, showcasing a potential role for cell traversal in the induction of effective adaptive responses. Taken together, these findings open up several interesting avenues for future research which will paint a clearer picture of innate immune responses to Plasmodium parasites