2,102 research outputs found
Observability of Hypergraphs
In this paper we develop a framework to study observability for uniform
hypergraphs. Hypergraphs are generalizations of graphs in which edges may
connect any number of nodes, thereby representing multi-way relationships which
are ubiquitous in many real-world networks including neuroscience, social
networks, and bioinformatics. We define a canonical multilinear dynamical
system with linear outputs on uniform hypergraphs which captures such multi-way
interactions and results in a homogeneous polynomial system. We derive a
Kalman-rank-like condition for assessing the local weak observability of this
resulting system and propose techniques for its efficient computation. We also
propose a greedy heuristic to determine the minimum set of observable nodes,
and demonstrate our approach numerically on different hypergraph topologies,
and hypergraphs derived from an experimental biological dataset.Comment: 7 pages, 3 figures, 2 algorithms, lots of math
Kronecker Product of Tensors and Hypergraphs: Structure and Dynamics
Hypergraphs and graph products extend traditional graph theory by
incorporating multi-way and coupled relationships, which are ubiquitous in
real-world systems. While the Kronecker product, rooted in matrix analysis, has
become a powerful tool in network science, its application has been limited to
pairwise networks. In this paper, we extend the coupling of graph products to
hypergraphs, enabling a system-theoretic analysis of network compositions
formed via the Kronecker product of hypergraphs. We first extend the notion of
the matrix Kronecker product to the tensor Kronecker product from the
perspective of tensor blocks. We present various algebraic and spectral
properties and express different tensor decompositions with the tensor
Kronecker product. Furthermore, we study the structure and dynamics of
Kronecker hypergraphs based on the tensor Kronecker product. We establish
conditions that enable the analysis of the trajectory and stability of a
hypergraph dynamical system by examining the dynamics of its factor
hypergraphs. Finally, we demonstrate the numerical advantage of this framework
for computing various tensor decompositions and spectral properties.Comment: 29 pages, 4 figures, 2 table
mage: Fluid Moves Between Code and Graphical Work in Computational Notebooks
We aim to increase the flexibility at which a data worker can choose the
right tool for the job, regardless of whether the tool is a code library or an
interactive graphical user interface (GUI). To achieve this flexibility, we
extend computational notebooks with a new API mage, which supports tools that
can represent themselves as both code and GUI as needed. We discuss the design
of mage as well as design opportunities in the space of flexible code/GUI tools
for data work. To understand tooling needs, we conduct a study with nine
professional practitioners and elicit their feedback on mage and potential
areas for flexible code/GUI tooling. We then implement six client tools for
mage that illustrate the main themes of our study findings. Finally, we discuss
open challenges in providing flexible code/GUI interactions for data workers
Antibody attributes that predict the neutralization and effector function of polyclonal responses to SARS-CoV-2
BACKGROUND: While antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. METHODS: We employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. RESULTS: To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. CONCLUSIONS: Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions
Îą-Actinin and Filamin Cooperatively Enhance the Stiffness of Actin Filament Networks
BACKGROUND: The close subcellular proximity of different actin filament crosslinking proteins suggests that these proteins may cooperate to organize F-actin structures to drive complex cellular functions during cell adhesion, motility and division. Here we hypothesize that alpha-actinin and filamin, two major F-actin crosslinking proteins that are both present in the lamella of adherent cells, display synergistic mechanical functions. METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative rheology, we find that combining alpha-actinin and filamin is much more effective at producing elastic, solid-like actin filament networks than alpha-actinin and filamin separately. Moreover, F-actin networks assembled in the presence of alpha-actinin and filamin strain-harden more readily than networks in the presence of either alpha-actinin or filamin. SIGNIFICANCE: These results suggest that cells combine auxiliary proteins with similar ability to crosslink filaments to generate stiff cytoskeletal structures, which are required for the production of internal propulsive forces for cell migration, and that these proteins do not have redundant mechanical functions
Pharmacogenomics of statin-related myopathy:Meta-analysis of rare variants from whole-exome sequencing
AIMS:Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM. METHODS AND RESULTS:SRM 3-5 cases (N = 505) and statin treatment-tolerant controls (N = 2047) were recruited from multiple sites in North America and Europe. SRM 3-5 was defined as symptoms consistent with muscle injury and an elevated creatine phosphokinase level >4 times upper limit of normal without another likely cause of muscle injury. Whole-exome sequencing and variant calling was coordinated from two analysis centres, and results of single-variant and gene-based burden tests were meta-analysed. No genome-wide significant associations were identified. Given the large number of cases, we had 80% power to identify a variant with minor allele frequency of 0.01 that increases the risk of SRM 6-fold at genome-wide significance. CONCLUSIONS:In this large whole-exome sequencing study of severe statin-related muscle injury conducted to date, we did not find evidence that rare coding variants are responsible for this adverse drug reaction. Larger sample sizes would be required to identify rare variants with small effects, but it is unclear whether such findings would be clinically actionable
Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast
BACKGROUND: BAHD acyltransferases, named after the first four biochemically characterized enzymes of the group, are plant-specific enzymes that catalyze the transfer of coenzyme A-activated donors onto various acceptor molecules. They are responsible for the synthesis in plants of a myriad of secondary metabolites, some of which are beneficial for humans either as therapeutics or as specialty chemicals such as flavors and fragrances. The production of pharmaceutical, nutraceutical and commodity chemicals using engineered microbes is an alternative, green route to energy-intensive chemical syntheses that consume petroleum-based precursors. However, identification of appropriate enzymes and validation of their functional expression in heterologous hosts is a prerequisite for the design and implementation of metabolic pathways in microbes for the synthesis of such target chemicals. RESULTS: For the synthesis of valuable metabolites in the yeast Saccharomyces cerevisiae, we selected BAHD acyltransferases based on their preferred donor and acceptor substrates. In particular, BAHDs that use hydroxycinnamoyl-CoAs and/or benzoyl-CoA as donors were targeted because a large number of molecules beneficial to humans belong to this family of hydroxycinnamate and benzoate conjugates. The selected BAHD coding sequences were synthesized and cloned individually on a vector containing the Arabidopsis gene At4CL5, which encodes a promiscuous 4-coumarate:CoA ligase active on hydroxycinnamates and benzoates. The various S. cerevisiae strains obtained for co-expression of At4CL5 with the different BAHDs effectively produced a wide array of valuable hydroxycinnamate and benzoate conjugates upon addition of adequate combinations of donors and acceptor molecules. In particular, we report here for the first time the production in yeast of rosmarinic acid and its derivatives, quinate hydroxycinnamate esters such as chlorogenic acid, and glycerol hydroxycinnamate esters. Similarly, we achieved for the first time the microbial production of polyamine hydroxycinnamate amides; monolignol, malate and fatty alcohol hydroxycinnamate esters; tropane alkaloids; and benzoate/caffeate alcohol esters. In some instances, the additional expression of Flavobacterium johnsoniae tyrosine ammonia-lyase (FjTAL) allowed the synthesis of p-coumarate conjugates and eliminated the need to supplement the culture media with 4-hydroxycinnamate. CONCLUSION: We demonstrate in this study the effectiveness of expressing members of the plant BAHD acyltransferase family in yeast for the synthesis of numerous valuable hydroxycinnamate and benzoate conjugates
Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self-Assembled Materials Based on Azo-Dyes
Three series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained
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