An intelligent tutoring system for space shuttle diagnosis

An Intelligent Tutoring System (ITS) transcends conventional computer-based instruction. An ITS is capable of monitoring and understanding student performance thereby providing feedback, explanation, and remediation. This is accomplished by including models of the student, the instructor, and the expert technician or operator in the domain of interest. The space shuttle fuel cell is the technical domain for the project described below. One system, Microcomputer Intelligence for Technical Training (MITT), demonstrates that ITS's can be developed and delivered, with a reasonable amount of effort and in a short period of time, on a microcomputer. The MITT system capitalizes on the diagnostic training approach called Framework for Aiding the Understanding of Logical Troubleshooting (FAULT) (Johnson, 1987). The system's embedded procedural expert was developed with NASA's C-Language Integrated Production (CLIP) expert system shell (Cubert, 1987)

PyLipID : A Python package for analysis of protein-lipid interactions from MD simulations

Lipids play important modulatory and structural roles for membrane proteins. Molecular dynamics simulations are frequently used to provide insights into the nature of these protein–lipid interactions. Systematic comparative analysis requires tools that provide algorithms for objective assessment of such interactions. We introduce PyLipID, a Python package for the identification and characterization of specific lipid interactions and binding sites on membrane proteins from molecular dynamics simulations. PyLipID uses a community analysis approach for binding site detection, calculating lipid residence times for both the individual protein residues and the detected binding sites. To assist structural analysis, PyLipID produces representative bound lipid poses from simulation data, using a density-based scoring function. To estimate residue contacts robustly, PyLipID uses a dual-cutoff scheme to differentiate between lipid conformational rearrangements while bound from full dissociation events. In addition to the characterization of protein–lipid interactions, PyLipID is applicable to analysis of the interactions of membrane proteins with other ligands. By combining automated analysis, efficient algorithms, and open-source distribution, PyLipID facilitates the systematic analysis of lipid interactions from large simulation data sets of multiple species of membrane proteins

Human gut Faecalibacterium prausnitzii deploy a highly efficient conserved system to cross-feed on β-mannan-derived oligosaccharides

ACKNOWLEDGMENTS We are grateful for support from The Research Council of Norway (FRIPRO program to P.B.P.: 250479; BIONÆR program to B.W.: 244259), the European Research Commission Starting Grant Fellowship (awarded to P.B.P.; 336355 MicroDE), and the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS) (for P.L. and S.H.D.). S.L.L.R. generated constructs and performed recombinant protein production and purification and functional characterizations of the binding protein and GHs. L.J.L., S.L., and L.M. expressed, purified, and performed functional characterization of FpCE2 and FpCE17. Growth experiments on mannans and SCFA quantifications were performed by G.L. ITC was performed by Å.K.R., Z.L., and L.S.M. G.V.P. and S.L.L.R. conducted the human metagenomic analysis. S.L.L.R., P.B.P., and B.W. conceived the study and supervised research. The manuscript was written primarily by S.L.L.R. with contributions from P.B.P., S.H.D., G.L, L.M., S.L., G.V.P., E.C.M., L.S.M., B.W., and L.J.L. Figures were prepared by S.L.L.R. We declare that we have no competing interests. Funding Information: We are grateful for support from The Research Council of Norway (FRIPRO program to P.B.P.: 250479; BIONÆR program to B.W.: 244259), the European Research Commission Starting Grant Fellowship (awarded to P.B.P.; 336355 MicroDE), and the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS) (for P.L. and S.H.D.).Peer reviewedPublisher PD

Theories for influencer identification in complex networks

In social and biological systems, the structural heterogeneity of interaction networks gives rise to the emergence of a small set of influential nodes, or influencers, in a series of dynamical processes. Although much smaller than the entire network, these influencers were observed to be able to shape the collective dynamics of large populations in different contexts. As such, the successful identification of influencers should have profound implications in various real-world spreading dynamics such as viral marketing, epidemic outbreaks and cascading failure. In this chapter, we first summarize the centrality-based approach in finding single influencers in complex networks, and then discuss the more complicated problem of locating multiple influencers from a collective point of view. Progress rooted in collective influence theory, belief-propagation and computer science will be presented. Finally, we present some applications of influencer identification in diverse real-world systems, including online social platforms, scientific publication, brain networks and socioeconomic systems.Comment: 24 pages, 6 figure

Catechol Polymers for pH-Responsive, Targeted Drug Delivery to Cancer Cells

A novel cell-targeting, pH-sensitive polymeric carrier was employed in this study for delivery of the anticancer drug bortezomib (BTZ) to cancer cells. Our strategy is based on facile conjugation of BTZ to catechol-containing polymeric carriers that are designed to be taken up selectively by cancer cells through cell surface receptor-mediated mechanisms. The polymer used as a building block in this study was poly(ethylene glycol), which was chosen for its ability to reduce nonspecific interactions with proteins and cells. The catechol moiety was exploited for its ability to bind and release borate-containing therapeutics such as BTZ in a pH-dependent manner. In acidic environments, such as in cancer tissue or the subcellular endosome, BTZ dissociates from the polymer-bound catechol groups to liberate the free drug, which inhibits proteasome function. A cancer-cell-targeting ligand, biotin, was presented on the polymer carriers to facilitate targeted entry of drug-loaded polymer carriers into cancer cells. Our study demonstrated that the cancer-targeting drug-polymer conjugates dramatically enhanced cellular uptake, proteasome inhibition, and cytotoxicity toward breast carcinoma cells in comparison with nontargeting drug-polymer conjugates. The pH-sensitive catechol-boronate binding mechanism provides a chemoselective approach for controlling the release of BTZ in targeted cancer cells, establishing a concept that may be applied in the future toward other boronic acid-containing therapeutics to treat a broad range of diseases

LipIDens : simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins

Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities

KELT-14b and KELT-15b: an independent discovery of WASP-122b and a new hot Jupiter

We report the discovery of KELT-14b and KELT-15b, two hot Jupiters from the KELT-South survey. KELT-14b, an independent discovery of the recently announced WASP-122b, is an inflated Jupiter mass planet that orbits a similar to 5.0(-0.7)(+0.3) (0)7 Gyr, V= 11.0, G2 star that is near the main sequence turnoff. The host star, KELT-14 (TYC 7638-981-1), has an inferred mass M* = 1.18(-0.7)(+0.3) M-circle dot and radius R* = 1.37 +/- -0.08 R-circle dot), and has T-eff = 58021 K, log g* = 4.23(-0.7)(+0.3) SI and [Fe/H] = 0.33 +/- -0.09. The planet orbits with a period of 1.7100588 +/- 0.0000025 days (T-0 = 2457091.02863 +/- 0.00047) and has a radius R-p = 1.521 Ri and mass Mp = 1.196 +/- 0.072 MI, and the eccentricity is consistent with zero. KELT-15b is another inflated Jupiter mass planet that orbits a similar to 4.6(-0.4)(+0.5) Gyr, V = 11.2, GO star (TYC 8146-86-1) that is near the 'blue hook' stage of evolution prior to the Hertzsprung gap, and has an inferred mass M* = 1.181(0.050)(+0.05) M-circle dot and radius R* = 1.481 R-circle dot, and T-eff = 6003-% K, log g* = 4.17(-0.04)(+0.02) and [Fe/H] = 0.05 +/- 0.03. The planet orbits on a period of 3.329441 +/- 0.000016 days (T0 = 2457029.1663 0.0073) and has a radius Rp = 1.443 (o)Ols7 Ri and mass M-p = 0.91 531 MI and an eccentricity consistent with zero. KELT-14b has the second largest expected emission signal in the K-band for known transiting planets brighter than K < 10.5. Both KELT-14b and KELT-15b are predicted to have large enough emission signals that their secondary eclipses should be detectable using ground-based observatories

The Impact of Advocacy Organizations on Low-Income Housing Policy in U.S. Cities

Financial support for affordable housing competes with many other municipal priorities. This work seeks to explain the variation in support for affordable housing among U.S. cities with populations of 100,000 or more. Using multivariate statistical analysis, this research investigates political explanations for the level of city expenditures on housing and community with a particular interest in the influence of housing advocacy organizations (AOs). Data for the model were gathered from secondary sources, including the U.S. Census and the National Center for Charitable Statistics. Among other results, the analysis indicates that, on average, the political maturity of AOs has a statistically significant, positive effect on local housing and community development expenditures