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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Machine learning 19 (1995), S. 95-131 
    ISSN: 0885-6125
    Keywords: theory revision ; knowledge refinement ; inductive logic programming
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract Knowledge acquisition is a difficult, error-prone, and time-consuming task. The task of automatically improving an existing knowledge base using learning methods is addressed by the class of systems performingtheory refinement. This paper presents a system,Forte (First-Order Revision of Theories from Examples), which refines first-order Horn-clause theories by integrating a variety of different revision techniques into a coherent whole.Forte uses these techniques within a hill-climbing framework, guided by a global heuristic. It identifies possible errors in the theory and calls on a library of operators to develop possible revisions. The best revision is implemented, and the process repeats until no further revisions are possible. Operators are drawn from a variety of sources, including propositional theory refinement, first-order induction, and inverse resolution.Forte is demonstrated in several domains, including logic programming and qualitative modelling.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Machine learning 19 (1995), S. 95-131 
    ISSN: 0885-6125
    Keywords: theory revision ; knowledge refinement ; inductive logic programming
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract Knowledge acquisition is a difficult, error-prone, and time-consuming task. The task of automatically improving an existing knowledge base using learning methods is addressed by the class of systems performing theory refinement. This paper presents a system, forte (First-Order Revision of Theories from Examples), which refines first-order Horn-clause theories by integrating a variety of different revision techniques into a coherent whole. FORTE uses these techniques within a hill-climbing framework, guided by a global heuristic. It identifies possible errors in the theory and calls on a library of operators to develop possible revisions. The best revision is implemented, and the process repeats until no further revisions are possible. Operators are drawn from a variety of sources, including prepositional theory refinement, first-order induction, and inverse resolution. FORTE is demonstrated in several domains, including logic programming and qualitative modelling.
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  • 3
    ISSN: 1432-2048
    Keywords: Key words: Bradyrhizobium ; Exopolysaccharide ; Glycine (nodulation) ; Lectin binding (soybean) ; Symbiosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract.  The exact mechanism(s) of infection and symbiotic development between rhizobia and legumes is not yet known, but changes in rhizobial exopolysaccharides (EPSs) affect both infection and nodule development of the legume host. Early events in the symbiotic process between Bradyrhizobium japonicum and soybean (Glycinemax [L.] Merr.) were studied using two mutants, defective in soybean lectin (SBL) binding, which had been generated from B. japonicum 2143 (USDA 3I-1b-143 derivative) by Tn5 mutagenesis. In addition to their SBL-binding deficiency, these mutants produced less EPS than the parental strain. The composition of EPS varied with the genotype and with the carbon source used for growth. When grown on arabinose, gluconate, or mannitol, the wild-type parental strain, B. japonicum 2143, produced EPS typical of DNA homology group I Bradyrhizobium, designated EPS I. When grown on malate, strain 2143 produced a different EPS composed only of galactose and its acetylated derivative and designated EPS II. Mutant 1252 produced EPS II when grown on arabinose or malate, but when grown on gluconate or mannitol, mutant 1252 produced a different EPS comprised of glucose, galactose, xylose and glucuronic acid (1:5:1:1) and designated EPS III. Mutant 1251, grown on any of these carbon sources, produced EPS III. The EPS of strain 2143 and mutant 1252 contained SBL-binding polysaccharide. The amount of the SBL-binding polysaccharide produced by mutant 1252 varied with the carbon source used for growth. The capsular polysaccharide (CPS) produced by strain 2143 during growth on arabinose, gluconate or mannitol, showed a high level of SBL binding, whereas CPS produced during growth of strain 2143 on malate showed a low level of SBL binding. However, the change in EPS composition and SBL binding of strain 2143 grown on malate did not affect the wild-type nodulation and nitrogen fixation phenotype of 2143. Mutant 1251, which produced EPS III, nodulated 2 d later than parental strain 2143, but formed effective, nitrogen-fixing tap root nodules. Mutant 1252, which produced either EPS II or III, however nodulated 5–6 d later and formed few and ineffective tap root nodules. Restoration of EPS I production in mutant 1252 correlated with restored SBL binding, but not with wild-type nodulation and nitrogen fixation.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Environmental monitoring and assessment 57 (1999), S. 85-107 
    ISSN: 1573-2959
    Keywords: Kissimmee River ; mercury ; nutrients ; restoration ; water quality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract The planned restoration of the Kissimmee River ecocystem will backfill approximately 35 km of flood control canal (C-38) that cuts through the meandering river channel, re-establish natural flow patterns, and restore the river/floodplain ecosystem. Water quality monitoring, including nutrients, total suspended solids (TSS), turbidity, dissolved oxygen (DO), and mercury, was conducted during a pilot `test fill' project to determine if soil disturbance during canal backfilling would negatively impact these water quality constituents. Surface water nutrient concentrations varied little between sites. Generally, highest concentrations occurred prior to construction, with lowest concentrations occurring during and after construction. During construction, TSS concentrations increased at sites immediately upstream, downstream, and adjacent to the construction area. Increased turbidity was generally restricted to areas immediately upstream and downstream of the test plug, with maximum levels occurring during the initial construction phase. Some downstream increases in turbidity were observed; however, impacts were short-term, lasting less than 24 h. Depresssed DO levels (〈2 mg/l) were observed upstream of the test plug following completion of the initial plug across C-38. Dissolved oxygen levels remained low for approximately 6 weeks, with no apparent ecological impacts. Total mercury (HgT) within canal sediment ranged from 9.2–180 ng/g and methylmercury concentrations ranged from 0.037–0.708 ng/g. Concentration of total mercury and total methylmercury (MeHgT) in the backfill material were much lower than concentrations in the canal sediment. No significant change in aqueous HgT concentrations occurred over the sampling period, although construction-induced turbidity could have temporarily caused a slightly elevated concentration immediately downstream of the construction site. Methylmercury concentrations in the water column ranged from 0.033–0.518 ng/l. No significant differences in mean MeHgT concentrations occured between sites or between sampling dates, except at one downstream site where MeHgT declined significantly over the sampling period.
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  • 5
    Publication Date: 2018-03-26
    Description: The facile rearrangement of “S-acyl isopeptides” to native peptide bonds via S,N-acyl shift is central to the success of native chemical ligation, the widely used approach for protein total synthesis. Proximity-driven amide bond formation via acyl transfer reactions in other contexts has proven generally less effective. Here, we show that under neutral aqueous conditions, “O-acyl isopeptides” derived from hydroxy-asparagine [aspartic acid-β-hydroxamic acid; Asp(β-HA)] rearrange to form native peptide bonds via an O,N-acyl shift. This process constitutes a rare example of an O,N-acyl shift that proceeds rapidly across a medium-size ring (t1/2 ∼ 15 min), and takes place in water with minimal interference from hydrolysis. In contrast to serine/threonine or tyrosine, which form O-acyl isopeptides only by the use of highly activated acyl donors and appropriate protecting groups in organic solvent, Asp(β-HA) is sufficiently reactive to form O-acyl isopeptides by treatment with an unprotected peptide-αthioester, at low mM concentration, in water. These findings were applied to an acyl transfer-based chemical ligation strategy, in which an unprotected N-terminal Asp(β-HA)-peptide and peptide-αthioester react under aqueous conditions to give a ligation product ultimately linked by a native peptide bond.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 1993-07-15
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2018-05-21
    Description: Chemical methods have enabled the total synthesis of protein molecules of ever-increasing size and complexity. However, methods to engineer synthetic proteins comprising noncanonical amino acids have not kept pace, even though this capability would be a distinct advantage of the total synthesis approach to protein science. In this work, we report a platform for protein engineering based on the screening of synthetic one-bead one-compound protein libraries. Screening throughput approaching that of cell surface display was achieved by a combination of magnetic bead enrichment, flow cytometry analysis of on-bead screens, and high-throughput MS/MS-based sequencing of identified active compounds. Direct screening of a synthetic protein library by these methods resulted in the de novo discovery of mirror-image miniprotein-based binders to a ∼150-kDa protein target, a task that would be difficult or impossible by other means.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 8
    Publication Date: 2017-11-20
    Description: The influenza M2 protein not only forms a proton channel but also mediates membrane scission in a cholesterol-dependent manner to cause virus budding and release. The atomic interaction of cholesterol with M2, as with most eukaryotic membrane proteins, has long been elusive. We have now determined the cholesterol-binding site of the M2 protein in phospholipid bilayers using solid-state NMR spectroscopy. Chain-fluorinated cholesterol was used to measure cholesterol proximity to M2 while sterol-deuterated cholesterol was used to measure bound-cholesterol orientation in lipid bilayers. Carbon–fluorine distance measurements show that at a cholesterol concentration of 17 mol%, two cholesterol molecules bind each M2 tetramer. Cholesterol binds the C-terminal transmembrane (TM) residues, near an amphipathic helix, without requiring a cholesterol recognition sequence motif. Deuterium NMR spectra indicate that bound cholesterol is approximately parallel to the bilayer normal, with the rough face of the sterol rings apposed to methyl-rich TM residues. The distance- and orientation-restrained cholesterol-binding site structure shows that cholesterol is stabilized by hydrophobic interactions with the TM helix and polar and aromatic interactions with neighboring amphipathic helices. At the 1:2 binding stoichiometry, lipid 31P spectra show an isotropic peak indicative of high membrane curvature. This M2–cholesterol complex structure, together with previously observed M2 localization at phase boundaries, suggests that cholesterol mediates M2 clustering to the neck of the budding virus to cause the necessary curvature for membrane scission. The solid-state NMR approach developed here is generally applicable for elucidating the structural basis of cholesterol’s effects on membrane protein function.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2020-07-06
    Description: The human brain is organized into large-scale networks identifiable using resting-state functional connectivity (RSFC). These functional networks correspond with broad cognitive domains; for example, the Default-mode network (DMN) is engaged during internally oriented cognition. However, functional networks may contain hierarchical substructures corresponding with more specific cognitive functions. Here, we used individual-specific precision RSFC to test whether network substructures could be identified in 10 healthy human brains. Across all subjects and networks, individualized network subdivisions were more valid—more internally homogeneous and better matching spatial patterns of task activation—than canonical networks. These measures of validity were maximized at a hierarchical scale that contained ∼83 subnetworks across the brain. At this scale, nine DMN subnetworks exhibited topographical similarity across subjects, suggesting that this approach identifies homologous neurobiological circuits across individuals. Some DMN subnetworks matched known features of brain organization corresponding with cognitive functions. Other subnetworks represented separate streams by which DMN couples with other canonical large-scale networks, including language and control networks. Together, this work provides a detailed organizational framework for studying the DMN in individual humans.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 10
    Publication Date: 2011-01-01
    Print ISSN: 0038-0938
    Electronic ISSN: 1573-093X
    Topics: Physics
    Published by Springer
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