Approximate Causal Abstraction

Scientific models describe natural phenomena at different levels of abstraction. Abstract descriptions can provide the basis for interventions on the system and explanation of observed phenomena at a level of granularity that is coarser than the most fundamental account of the system. Beckers and Halpern (2019), building on work of Rubenstein et al. (2017), developed an account of abstraction for causal models that is exact. Here we extend this account to the more realistic case where an abstract causal model offers only an approximation of the underlying system. We show how the resulting account handles the discrepancy that can arise between low- and high-level causal models of the same system, and in the process provide an account of how one causal model approximates another, a topic of independent interest. Finally, we extend the account of approximate abstractions to probabilistic causal models, indicating how and where uncertainty can enter into an approximate abstraction

Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of glycoside hydrolase.

BackgroundGut microbiome metagenomics has revealed many protein families and domains found largely or exclusively in that environment. Proteins containing the GxGYxYP domain are over-represented in the gut microbiota, and are found in Polysaccharide Utilization Loci in the gut symbiont Bacteroides thetaiotaomicron, suggesting their involvement in polysaccharide metabolism, but little else is known of the function of this domain.ResultsGenomic context and domain architecture analyses support a role for the GxGYxYP domain in carbohydrate metabolism. Sparse occurrences in eukaryotes are the result of lateral gene transfer. The structure of the GxGYxYP domain-containing protein encoded by the BT2193 locus reveals two structural domains, the first composed of three divergent repeats with no recognisable homology to previously solved structures, the second a more familiar seven-stranded β/α barrel. Structure-based analyses including conservation mapping localise a presumed functional site to a cleft between the two domains of BT2193. Matching to a catalytic site template from a GH9 cellulase and other analyses point to a putative catalytic triad composed of Glu272, Asp331 and Asp333.ConclusionsWe suggest that GxGYxYP-containing proteins constitute a novel glycoside hydrolase family of as yet unknown specificity

Approximate Causal Abstraction

Scientific models describe natural phenomena at different levels of abstraction. Abstract descriptions can provide the basis for interventions on the system and explanation of observed phenomena at a level of granularity that is coarser than the most fundamental account of the system. Beckers and Halpern (2019), building on work of Rubenstein et al. (2017), developed an account of abstraction for causal models that is exact. Here we extend this account to the more realistic case where an abstract causal model offers only an approximation of the underlying system. We show how the resulting account handles the discrepancy that can arise between low- and high-level causal models of the same system, and in the process provide an account of how one causal model approximates another, a topic of independent interest. Finally, we extend the account of approximate abstractions to probabilistic causal models, indicating how and where uncertainty can enter into an approximate abstraction

Structural genomics analysis of uncharacterized protein families overrepresented in human gut bacteria identifies a novel glycoside hydrolase.

BackgroundBacteroides spp. form a significant part of our gut microbiome and are well known for optimized metabolism of diverse polysaccharides. Initial analysis of the archetypal Bacteroides thetaiotaomicron genome identified 172 glycosyl hydrolases and a large number of uncharacterized proteins associated with polysaccharide metabolism.ResultsBT_1012 from Bacteroides thetaiotaomicron VPI-5482 is a protein of unknown function and a member of a large protein family consisting entirely of uncharacterized proteins. Initial sequence analysis predicted that this protein has two domains, one on the N- and one on the C-terminal. A PSI-BLAST search found over 150 full length and over 90 half size homologs consisting only of the N-terminal domain. The experimentally determined three-dimensional structure of the BT_1012 protein confirms its two-domain architecture and structural analysis of both domains suggests their specific functions. The N-terminal domain is a putative catalytic domain with significant similarity to known glycoside hydrolases, the C-terminal domain has a beta-sandwich fold typically found in C-terminal domains of other glycosyl hydrolases, however these domains are typically involved in substrate binding. We describe the structure of the BT_1012 protein and discuss its sequence-structure relationship and their possible functional implications.ConclusionsStructural and sequence analyses of the BT_1012 protein identifies it as a glycosyl hydrolase, expanding an already impressive catalog of enzymes involved in polysaccharide metabolism in Bacteroides spp. Based on this we have renamed the Pfam families representing the two domains found in the BT_1012 protein, PF13204 and PF12904, as putative glycoside hydrolase and glycoside hydrolase-associated C-terminal domain respectively

Two Pfam protein families characterized by a crystal structure of protein lpg2210 from Legionella pneumophila.

BackgroundEvery genome contains a large number of uncharacterized proteins that may encode entirely novel biological systems. Many of these uncharacterized proteins fall into related sequence families. By applying sequence and structural analysis we hope to provide insight into novel biology.ResultsWe analyze a previously uncharacterized Pfam protein family called DUF4424 [Pfam:PF14415]. The recently solved three-dimensional structure of the protein lpg2210 from Legionella pneumophila provides the first structural information pertaining to this family. This protein additionally includes the first representative structure of another Pfam family called the YARHG domain [Pfam:PF13308]. The Pfam family DUF4424 adopts a 19-stranded beta-sandwich fold that shows similarity to the N-terminal domain of leukotriene A-4 hydrolase. The YARHG domain forms an all-helical domain at the C-terminus. Structure analysis allows us to recognize distant similarities between the DUF4424 domain and individual domains of M1 aminopeptidases and tricorn proteases, which form massive proteasome-like capsids in both archaea and bacteria.ConclusionsBased on our analyses we hypothesize that the DUF4424 domain may have a role in forming large, multi-component enzyme complexes. We suggest that the YARGH domain may play a role in binding a moiety in proximity with peptidoglycan, such as a hydrophobic outer membrane lipid or lipopolysaccharide

LUD, a new protein domain associated with lactate utilization.

BackgroundA novel highly conserved protein domain, DUF162 [Pfam: PF02589], can be mapped to two proteins: LutB and LutC. Both proteins are encoded by a highly conserved LutABC operon, which has been implicated in lactate utilization in bacteria. Based on our analysis of its sequence, structure, and recent experimental evidence reported by other groups, we hereby redefine DUF162 as the LUD domain family.ResultsJCSG solved the first crystal structure [PDB:2G40] from the LUD domain family: LutC protein, encoded by ORF DR_1909, of Deinococcus radiodurans. LutC shares features with domains in the functionally diverse ISOCOT superfamily. We have observed that the LUD domain has an increased abundance in the human gut microbiome.ConclusionsWe propose a model for the substrate and cofactor binding and regulation in LUD domain. The significance of LUD-containing proteins in the human gut microbiome, and the implication of lactate metabolism in the radiation-resistance of Deinococcus radiodurans are discussed

Atomic Information Disclosure of Off-Chained Computations Using Threshold Encryption

Public Blockchains on their own are, by definition, incapable of keeping data private and disclosing it at a later time. Control over the eventual disclosure of private data must be maintained outside a Blockchain by withholding and later publishing encryption keys, for example. We propose the Atomic Information Disclosure (AID) pattern based on threshold encryption that allows a set of key holders to govern the release of data without having access to it. We motivate this pattern with problems that require independently reproduced solutions. By keeping submissions private until a deadline expires, participants are unable to plagiarise and must therefore generate their own solutions which can then be aggregated and analysed to determine a final answer. We outline the importance of a game-theoretically sound incentive scheme, possible attacks, and other future work

Comparison of ultracold neutron sources for fundamental physics measurements

Ultracold neutrons (UCNs) are key for precision studies of fundamental parameters of the neutron and in searches for new CP violating processes or exotic interactions beyond the Standard Model of particle physics. The most prominent example is the search for a permanent electric dipole moment of the neutron (nEDM). We have performed an experimental comparison of the leading UCN sources currently operating. We have used a 'standard' UCN storage bottle with a volume of 32 liters, comparable in size to nEDM experiments, which allows us to compare the UCN density available at a given beam port.Comment: 20 pages, 30 Figure