Doing Things Twice (Or Differently): Strategies to Identify Studies for Targeted Validation

The "reproducibility crisis" has been a highly visible source of scientific controversy and dispute. Here, I propose and review several avenues for identifying and prioritizing research studies for the purpose of targeted validation. Of the various proposals discussed, I identify scientific data science as being a strategy that merits greater attention among those interested in reproducibility. I argue that the tremendous potential of scientific data science for uncovering high-value research studies is a significant and rarely discussed benefit of the transition to a fully open-access publishing model.Comment: 4 page

Integrative biological simulation praxis: Considerations from physics, philosophy, and data/model curation practices

Integrative biological simulations have a varied and controversial history in the biological sciences. From computational models of organelles, cells, and simple organisms, to physiological models of tissues, organ systems, and ecosystems, a diverse array of biological systems have been the target of large-scale computational modeling efforts. Nonetheless, these research agendas have yet to prove decisively their value among the broader community of theoretical and experimental biologists. In this commentary, we examine a range of philosophical and practical issues relevant to understanding the potential of integrative simulations. We discuss the role of theory and modeling in different areas of physics and suggest that certain sub-disciplines of physics provide useful cultural analogies for imagining the future role of simulations in biological research. We examine philosophical issues related to modeling which consistently arise in discussions about integrative simulations and suggest a pragmatic viewpoint that balances a belief in philosophy with the recognition of the relative infancy of our state of philosophical understanding. Finally, we discuss community workflow and publication practices to allow research to be readily discoverable and amenable to incorporation into simulations. We argue that there are aligned incentives in widespread adoption of practices which will both advance the needs of integrative simulation efforts as well as other contemporary trends in the biological sciences, ranging from open science and data sharing to improving reproducibility.Comment: 10 page

Robust Computer Algebra, Theorem Proving, and Oracle AI

In the context of superintelligent AI systems, the term "oracle" has two meanings. One refers to modular systems queried for domain-specific tasks. Another usage, referring to a class of systems which may be useful for addressing the value alignment and AI control problems, is a superintelligent AI system that only answers questions. The aim of this manuscript is to survey contemporary research problems related to oracles which align with long-term research goals of AI safety. We examine existing question answering systems and argue that their high degree of architectural heterogeneity makes them poor candidates for rigorous analysis as oracles. On the other hand, we identify computer algebra systems (CASs) as being primitive examples of domain-specific oracles for mathematics and argue that efforts to integrate computer algebra systems with theorem provers, systems which have largely been developed independent of one another, provide a concrete set of problems related to the notion of provable safety that has emerged in the AI safety community. We review approaches to interfacing CASs with theorem provers, describe well-defined architectural deficiencies that have been identified with CASs, and suggest possible lines of research and practical software projects for scientists interested in AI safety.Comment: 15 pages, 3 figure

The specificities of small molecule inhibitors of the TGF beta and BMP pathways

Small molecule inhibitors of type 1 receptor serine threonine kinases (ALKs1-7), the mediators of TGF beta and BMP signals, have been employed extensively to assess their physiological roles in cells and organisms. While all of these inhibitors have been reported as "selective" inhibitors of specific ALKs, extensive specificity tests against a wide array of protein kinases have not been performed. In this study, we examine the specificities and potencies of the most frequently used small molecule inhibitors of the TGF beta pathway (SB-431542, SB-505124, LY-364947 and A-83-01) and the BMP pathway (Dorsomorphin and LDN-193189) against a panel of up to 123 protein kinases covering a broad spectrum of the human kinome. We demonstrate that the inhibitors of the TGF beta pathway are relatively more selective than the inhibitors of the BMP pathway. Based on our specificity and potency profile and published data, we recommend SB-505124 as the most suitable molecule for use as an inhibitor of ALKs 4,5 and 7 and the TGF beta pathway. We do not recommend Dorsomorphin, also called Compound C, for use as an inhibitor of the BMP pathway. Although LDN-193189, a Dorsomorphin derivative, is a very potent inhibitor of ALK2/3 and the BMP-pathway, we found that it potently inhibited a number of other protein kinases at concentrations sufficient to inhibit ALK2/3 and its use as a selective BMP-pathway inhibitor has to be considered cautiously. Our observations have highlighted the need for caution when using these small molecule inhibitors to assess the physiological roles of BMP and TGF beta pathways. (C) 2011 Elsevier Inc. All rights reserved. NOTICE: this is the author’s version of a work that was accepted for publication in Cellular Signalling. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cellular Signalling, [VOL 23, ISSUE 11, (2011)] DOI 10.1016/j.cellsig.2011.06.019</p

AI Safety and Reproducibility: Establishing Robust Foundations for the Neuropsychology of Human Values

We propose the creation of a systematic effort to identify and replicate key findings in neuropsychology and allied fields related to understanding human values. Our aim is to ensure that research underpinning the value alignment problem of artificial intelligence has been sufficiently validated to play a role in the design of AI systems.Comment: 5 page

Integrative Biological Simulation, Neuropsychology, and AI Safety

We describe a biologically-inspired research agenda with parallel tracks aimed at AI and AI safety. The bottom-up component consists of building a sequence of biophysically realistic simulations of simple organisms such as the nematode $Caenorhabditis$ $elegans$, the fruit fly $Drosophila$ $melanogaster$, and the zebrafish $Danio$ $rerio$ to serve as platforms for research into AI algorithms and system architectures. The top-down component consists of an approach to value alignment that grounds AI goal structures in neuropsychology, broadly considered. Our belief is that parallel pursuit of these tracks will inform the development of value-aligned AI systems that have been inspired by embodied organisms with sensorimotor integration. An important set of side benefits is that the research trajectories we describe here are grounded in long-standing intellectual traditions within existing research communities and funding structures. In addition, these research programs overlap with significant contemporary themes in the biological and psychological sciences such as data/model integration and reproducibility.Comment: 5 page

Reductionism and the Universal Calculus

In the seminal essay, "On the unreasonable effectiveness of mathematics in the physical sciences," physicist Eugene Wigner poses a fundamental philosophical question concerning the relationship between a physical system and our capacity to model its behavior with the symbolic language of mathematics. In this essay, I examine an ambitious 16th and 17th-century intellectual agenda from the perspective of Wigner's question, namely, what historian Paolo Rossi calls "the quest to create a universal language." While many elite thinkers pursued related ideas, the most inspiring and forceful was Gottfried Leibniz's effort to create a "universal calculus," a pictorial language which would transparently represent the entirety of human knowledge, as well as an associated symbolic calculus with which to model the behavior of physical systems and derive new truths. I suggest that a deeper understanding of why the efforts of Leibniz and others failed could shed light on Wigner's original question. I argue that the notion of reductionism is crucial to characterizing the failure of Leibniz's agenda, but that a decisive argument for the why the promises of this effort did not materialize is still lacking.Comment: 11 pages, 1 figur

Estimation of the growth curve parameters in Macrobrachium rosenbergii

Growth is one of the most important characteristics of cultured species. The objective of this study was to determine the fitness of linear, log linear, polynomial, exponential and Logistic functions to the growth curves of Macrobrachium rosenbergii obtained by using weekly records of live weight, total length, head length, claw length, and last segment length from 20 to 192 days of age. The models were evaluated according to the coefficient of determination (R2), and error sum off square (ESS) and helps in formulating breeders in selective breeding programs. Twenty full-sib families consisting 400 PLs each were stocked in 20 different hapas and reared till 8 weeks after which a total of 1200 animals were transferred to earthen ponds and reared up to 192 days. The R2 values of the models ranged from 56 – 96 in case of overall body weight with logistic model being the highest. The R2 value for total length ranged from 62 to 90 with logistic model being the highest. In case of head length, the R2 value ranged between 55 and 95 with logistic model being the highest. The R2 value for claw length ranged from 44 to 94 with logistic model being the highest. For last segment length, R2 value ranged from 55 – 80 with polynomial model being the highest. However, the log linear model registered low ESS value followed by linear model for overall body weight while exponential model showed low ESS value followed by log linear model in case of head length. For total length the low ESS value was given by log linear model followed by logistic model and for claw length exponential model showed low ESS value followed by log linear model. In case of last segment length, linear model showed lowest ESS value followed by log linear model. Since, the model that shows highest R2 value with low ESS value is generally considered as the best fit model. Among the five models tested, logistic model, log linear model and linear models were found to be the best models for overall body weight, total length and head length respectively. For claw length and last segment length, log linear model was found to be the best model. These models can be used to predict growth rates in M. rosenbergii. However, further studies need to be conducted with more growth traits taken into consideratio