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  • Biochemistry  (73)
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  • Articles  (93)
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  • 1
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-08-11
    Description: A parabolic relationship between lens radius and refractive index allows spherical lenses to avoid spherical aberration. We show that in squid, patchy colloidal physics resulted from an evolutionary radiation of globular S-crystallin proteins. Small-angle x-ray scattering experiments on lens tissue show colloidal gels of S-crystallins at all radial positions. Sparse lens materials form via low-valence linkages between disordered loops protruding from the protein surface. The loops are polydisperse and bind via a set of hydrogen bonds between disordered side chains. Peripheral lens regions with low particle valence form stable, volume-spanning gels at low density, whereas central regions with higher average valence gel at higher densities. The proteins demonstrate an evolved set of linkers for self-assembly of nanoparticles into volumetric materials.
    Keywords: Biochemistry
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  • 2
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-08-18
    Keywords: Biochemistry
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  • 3
    Publication Date: 2017-09-01
    Description: In the early stage of transcription, eukaryotic RNA polymerase II (Pol II) exchanges initiation factors with elongation factors to form an elongation complex for processive transcription. Here we report the structure of the Pol II elongation complex bound with the basal elongation factors Spt4/5, Elf1, and TFIIS. Spt4/5 (the Spt4/Spt5 complex) and Elf1 modify a wide area of the Pol II surface. Elf1 bridges the Pol II central cleft, completing a "DNA entry tunnel" for downstream DNA. Spt4 and the Spt5 NGN and KOW1 domains encircle the upstream DNA, constituting a "DNA exit tunnel." The Spt5 KOW4 and KOW5 domains augment the "RNA exit tunnel," directing the exiting nascent RNA. Thus, the elongation complex establishes a completely different transcription and regulation platform from that of the initiation complexes.
    Keywords: Biochemistry
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  • 4
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-09-01
    Keywords: Biochemistry
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  • 5
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-09-01
    Keywords: Biochemistry
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  • 6
    Publication Date: 2017-09-01
    Description: NAD + (oxidized form of NAD:nicotinamide adenine dinucleotide)–reducing soluble [NiFe]-hydrogenase (SH) is phylogenetically related to NADH (reduced form of NAD + ):quinone oxidoreductase (complex I), but the geometrical arrangements of the subunits and Fe–S clusters are unclear. Here, we describe the crystal structures of SH in the oxidized and reduced states. The cluster arrangement is similar to that of complex I, but the subunits orientation is not, which supports the hypothesis that subunits evolved as prebuilt modules. The oxidized active site includes a six-coordinate Ni, which is unprecedented for hydrogenases, whose coordination geometry would prevent O 2 from approaching. In the reduced state showing the normal active site structure without a physiological electron acceptor, the flavin mononucleotide cofactor is dissociated, which may be caused by the oxidation state change of nearby Fe–S clusters and may suppress production of reactive oxygen species.
    Keywords: Biochemistry
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  • 7
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-09-15
    Keywords: Biochemistry
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  • 8
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-06-23
    Keywords: Biochemistry
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  • 9
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-06-23
    Keywords: Biochemistry
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  • 10
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-08-11
    Keywords: Biochemistry
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  • 11
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-08-11
    Keywords: Biochemistry
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  • 12
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-08-11
    Keywords: Biochemistry
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  • 13
    Publication Date: 2017-08-11
    Description: Small basic proteins present in most Archaea share a common ancestor with the eukaryotic core histones. We report the crystal structure of an archaeal histone-DNA complex. DNA wraps around an extended polymer, formed by archaeal histone homodimers, in a quasi-continuous superhelix with the same geometry as DNA in the eukaryotic nucleosome. Substitutions of a conserved glycine at the interface of adjacent protein layers destabilize archaeal chromatin, reduce growth rate, and impair transcription regulation, confirming the biological importance of the polymeric structure. Our data establish that the histone-based mechanism of DNA compaction predates the nucleosome, illuminating the origin of the nucleosome.
    Keywords: Biochemistry
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  • 14
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-08-18
    Description: Vinculin is an actin-binding protein thought to reinforce cell-cell and cell-matrix adhesions. However, how mechanical load affects the vinculin–F-actin bond is unclear. Using a single-molecule optical trap assay, we found that vinculin forms a force-dependent catch bond with F-actin through its tail domain, but with lifetimes that depend strongly on the direction of the applied force. Force toward the pointed (–) end of the actin filament resulted in a bond that was maximally stable at 8 piconewtons, with a mean lifetime (12 seconds) 10 times as long as the mean lifetime when force was applied toward the barbed (+) end. A computational model of lamellipodial actin dynamics suggests that the directionality of the vinculin–F-actin bond could establish long-range order in the actin cytoskeleton. The directional and force-stabilized binding of vinculin to F-actin may be a mechanism by which adhesion complexes maintain front-rear asymmetry in migrating cells.
    Keywords: Biochemistry
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  • 15
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-09-01
    Keywords: Biochemistry
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  • 16
    Publication Date: 2017-06-02
    Description: The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health.
    Keywords: Biochemistry
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  • 17
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-06-02
    Keywords: Biochemistry
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  • 18
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-06-23
    Keywords: Biochemistry
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  • 19
    Publication Date: 2017-06-23
    Description: Hormones can transmit signals through adenosine 3',5'-monophosphate (cAMP) to precise intracellular locations. The fidelity of these responses relies on the activation of localized protein kinase A (PKA) holoenzymes. Association of PKA regulatory type II (RII) subunits with A-kinase–anchoring proteins (AKAPs) confers location, and catalytic (C) subunits phosphorylate substrates. Single-particle electron microscopy demonstrated that AKAP79 constrains RII-C subassemblies within 150 to 250 angstroms of its targets. Native mass spectrometry established that these macromolecular assemblies incorporated stoichiometric amounts of cAMP. Chemical-biology– and live cell–imaging techniques revealed that catalytically active PKA holoenzymes remained intact within the cytoplasm. These findings indicate that the parameters of anchored PKA holoenzyme action are much more restricted than originally anticipated.
    Keywords: Biochemistry
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  • 20
    Publication Date: 2017-06-23
    Description: The multifunctional protein cytochrome c (cyt c) plays key roles in electron transport and apoptosis, switching function by modulating bonding between a heme iron and the sulfur in a methionine residue. This Fe–S(Met) bond is too weak to persist in the absence of protein constraints. We ruptured the bond in ferrous cyt c using an optical laser pulse and monitored the bond reformation within the protein active site using ultrafast x-ray pulses from an x-ray free-electron laser, determining that the Fe–S(Met) bond enthalpy is ~4 kcal/mol stronger than in the absence of protein constraints. The 4 kcal/mol is comparable with calculations of stabilization effects in other systems, demonstrating how biological systems use an entatic state for modest yet accessible energetics to modulate chemical function.
    Keywords: Biochemistry
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  • 21
    Publication Date: 2017-07-21
    Description: Hsp100 polypeptide translocases are conserved members of the AAA+ family (adenosine triphosphatases associated with diverse cellular activities) that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase from Saccharomyces cerevisiae solubilizes stress-induced amorphous aggregates and amyloids. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo–electron microscopy structures at near-atomic resolution of Hsp104 in different translocation states. Substrate interactions are mediated by conserved, pore-loop tyrosines that contact an 80-angstrom-long unfolded polypeptide along the axial channel. Two protomers undergo a ratchet-like conformational change that advances pore loop–substrate interactions by two amino acids. These changes are coupled to activation of specific nucleotide hydrolysis sites and, when transmitted around the hexamer, reveal a processive rotary translocation mechanism and substrate-responsive flexibility during Hsp104-catalyzed disaggregation.
    Keywords: Biochemistry
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  • 22
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-07-28
    Keywords: Biochemistry
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  • 23
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-07-28
    Keywords: Biochemistry
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  • 24
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-07-28
    Keywords: Biochemistry
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  • 25
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-07-28
    Keywords: Biochemistry
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  • 26
    Publication Date: 2017-07-28
    Description: Ribosome stalling leads to recruitment of the ribosome quality control complex (RQC), which targets the partially synthesized polypeptide for proteasomal degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here we examined the role of CAT-tailing in nascent-chain degradation in budding yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines immediately proximal to the ribosome exit tunnel. For substrates without Ltn1p-accessible lysines, CAT-tailing enabled degradation by exposing lysines sequestered in the ribosome exit tunnel. Thus, CAT-tails do not serve as a degron, but rather provide a fail-safe mechanism that expands the range of RQC-degradable substrates.
    Keywords: Biochemistry
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  • 27
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-07-28
    Keywords: Biochemistry
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  • 28
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-09-30
    Keywords: Biochemistry
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  • 29
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-09-30
    Description: How fast can a cell locate a specific chromosomal DNA sequence specified by a single-stranded oligonucleotide? To address this question, we investigate the intracellular search processes of the Cas9 protein, which can be programmed by a guide RNA to bind essentially any DNA sequence. This targeting flexibility requires Cas9 to unwind the DNA double helix to test for correct base pairing to the guide RNA. Here we study the search mechanisms of the catalytically inactive Cas9 (dCas9) in living Escherichia coli by combining single-molecule fluorescence microscopy and bulk restriction-protection assays. We find that it takes a single fluorescently labeled dCas9 6 hours to find the correct target sequence, which implies that each potential target is bound for less than 30 milliseconds. Once bound, dCas9 remains associated until replication. To achieve fast targeting, both Cas9 and its guide RNA have to be present at high concentrations.
    Keywords: Biochemistry
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  • 30
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-10-13
    Keywords: Biochemistry
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  • 31
    Publication Date: 2017-10-13
    Description: A substantial fraction of the proteome is intrinsically disordered, and even well-folded proteins adopt non-native geometries during synthesis, folding, transport, and turnover. Characterization of intrinsically disordered proteins (IDPs) is challenging, in part because of a lack of accurate physical models and the difficulty of interpreting experimental results. We have developed a general method to extract the dimensions and solvent quality (self-interactions) of IDPs from a single small-angle x-ray scattering measurement. We applied this procedure to a variety of IDPs and found that even IDPs with low net charge and high hydrophobicity remain highly expanded in water, contrary to the general expectation that protein-like sequences collapse in water. Our results suggest that the unfolded state of most foldable sequences is expanded; we conjecture that this property was selected by evolution to minimize misfolding and aggregation.
    Keywords: Biochemistry
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  • 32
    Publication Date: 2017-10-06
    Description: Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer’s disease patients. We present the structure of an Aβ(1–42) fibril composed of two intertwined protofilaments determined by cryo–electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall "LS"-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed "groove" and "ridge," leading to different binding pathways on both fibril ends, which has implications for fibril growth.
    Keywords: Biochemistry
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  • 33
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-10-06
    Keywords: Biochemistry
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  • 34
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-11-17
    Keywords: Biochemistry
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  • 35
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-11-24
    Keywords: Biochemistry
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  • 36
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-11-17
    Description: Mitochondrial adenosine triphosphate (ATP) synthase produces the majority of ATP in eukaryotic cells, and its dimerization is necessary to create the inner membrane folds, or cristae, characteristic of mitochondria. Proton translocation through the membrane-embedded F O region turns the rotor that drives ATP synthesis in the soluble F 1 region. Although crystal structures of the F 1 region have illustrated how this rotation leads to ATP synthesis, understanding how proton translocation produces the rotation has been impeded by the lack of an experimental atomic model for the F O region. Using cryo–electron microscopy, we determined the structure of the dimeric F O complex from Saccharomyces cerevisiae at a resolution of 3.6 angstroms. The structure clarifies how the protons travel through the complex, how the complex dimerizes, and how the dimers bend the membrane to produce cristae.
    Keywords: Biochemistry
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  • 37
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-11-17
    Description: In bacteria, the activation of gene transcription at many promoters is simple and only involves a single activator. The cyclic adenosine 3',5'-monophosphate receptor protein (CAP), a classic activator, is able to activate transcription independently through two different mechanisms. Understanding the class I mechanism requires an intact transcription activation complex (TAC) structure at a high resolution. Here we report a high-resolution cryo–electron microscopy structure of an intact Escherichia coli class I TAC containing a CAP dimer, a 70 –RNA polymerase (RNAP) holoenzyme, a complete class I CAP-dependent promoter DNA, and a de novo synthesized RNA oligonucleotide. The structure shows how CAP wraps the upstream DNA and how the interactions recruit RNAP. Our study provides a structural basis for understanding how activators activate transcription through the class I recruitment mechanism.
    Keywords: Biochemistry
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  • 38
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-11-24
    Keywords: Biochemistry
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  • 39
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-11-17
    Keywords: Biochemistry
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  • 40
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-11-03
    Keywords: Biochemistry
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  • 41
    Publication Date: 2017-11-03
    Description: The Rift Valley fever virus (RVFV) is transmitted by infected mosquitoes, causing severe disease in humans and livestock across Africa. We determined the x-ray structure of the RVFV class II fusion protein Gc in its postfusion form and in complex with a glycerophospholipid (GPL) bound in a conserved cavity next to the fusion loop. Site-directed mutagenesis and molecular dynamics simulations further revealed a built-in motif allowing en bloc insertion of the fusion loop into membranes, making few nonpolar side-chain interactions with the aliphatic moiety and multiple polar interactions with lipid head groups upon membrane restructuring. The GPL head-group recognition pocket is conserved in the fusion proteins of other arthropod-borne viruses, such as Zika and chikungunya viruses, which have recently caused major epidemics worldwide.
    Keywords: Biochemistry
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  • 42
    Publication Date: 2017-05-12
    Description: Multiple human diseases ensue from a hereditary or acquired deficiency of iron-transporting protein function that diminishes transmembrane iron flux in distinct sites and directions. Because other iron-transport proteins remain active, labile iron gradients build up across the corresponding protein-deficient membranes. Here we report that a small-molecule natural product, hinokitiol, can harness such gradients to restore iron transport into, within, and/or out of cells. The same compound promotes gut iron absorption in DMT1-deficient rats and ferroportin-deficient mice, as well as hemoglobinization in DMT1- and mitoferrin-deficient zebrafish. These findings illuminate a general mechanistic framework for small molecule–mediated site- and direction-selective restoration of iron transport. They also suggest that small molecules that partially mimic the function of missing protein transporters of iron, and possibly other ions, may have potential in treating human diseases.
    Keywords: Biochemistry
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  • 43
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-05-19
    Keywords: Biochemistry
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  • 44
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-05-19
    Description: Hydrotropes are small molecules that solubilize hydrophobic molecules in aqueous solutions. Typically, hydrotropes are amphiphilic molecules and differ from classical surfactants in that they have low cooperativity of aggregation and work at molar concentrations. Here, we show that adenosine triphosphate (ATP) has properties of a biological hydrotrope. It can both prevent the formation of and dissolve previously formed protein aggregates. This chemical property is manifested at physiological concentrations between 5 and 10 millimolar. Therefore, in addition to being an energy source for biological reactions, for which micromolar concentrations are sufficient, we propose that millimolar concentrations of ATP may act to keep proteins soluble. This may in part explain why ATP is maintained in such high concentrations in cells.
    Keywords: Biochemistry
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  • 45
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-05-12
    Keywords: Biochemistry
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  • 46
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-04-14
    Description: Author: Julia Fahrenkamp-Uppenbrink
    Keywords: Biochemistry
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  • 47
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-04-15
    Keywords: Biochemistry
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  • 48
    Publication Date: 2017-04-15
    Description: Nucleosomes are dynamic entities that are repositioned along DNA by chromatin remodeling processes. A nucleosome repositioned by the switch-sucrose nonfermentable (SWI/SNF) remodeler collides with a neighbor and forms the intermediate "overlapping dinucleosome." Here, we report the crystal structure of the overlapping dinucleosome, in which two nucleosomes are associated, at 3.14-angstrom resolution. In the overlapping dinucleosome structure, the unusual "hexasome" nucleosome, composed of the histone hexamer lacking one H2A-H2B dimer from the conventional histone octamer, contacts the canonical "octasome" nucleosome, and they intimately associate. Consequently, about 250 base pairs of DNA are left-handedly wrapped in three turns, without a linker DNA segment between the hexasome and octasome moieties. The overlapping dinucleosome structure may provide important information to understand how nucleosome repositioning occurs during the chromatin remodeling process.
    Keywords: Biochemistry
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  • 49
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-02-10
    Description: Author: Jake Yeston
    Keywords: Inorganic Chemistry
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  • 50
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-04-15
    Description: DNA transcription is functionally coupled to messenger RNA (mRNA) translation in bacteria, but how this is achieved remains unclear. Here we show that RNA polymerase (RNAP) and the ribosome of Escherichia coli can form a defined transcribing and translating "expressome" complex. The cryo–electron microscopic structure of the expressome reveals continuous protection of ~30 nucleotides of mRNA extending from the RNAP active center to the ribosome decoding center. The RNAP-ribosome interface includes the RNAP subunit α carboxyl-terminal domain, which is required for RNAP-ribosome interaction in vitro and for pronounced cell growth defects upon translation inhibition in vivo, consistent with its function in transcription-translation coupling. The expressome structure can only form during transcription elongation and explains how translation can prevent transcriptional pausing, backtracking, and termination.
    Keywords: Biochemistry
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  • 51
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-04-15
    Keywords: Biochemistry
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  • 52
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-04-15
    Keywords: Biochemistry
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  • 53
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-01-27
    Description: Author: Jake Yeston
    Keywords: Inorganic Chemistry
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  • 54
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-10-20
    Keywords: Biochemistry
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  • 55
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-10-20
    Keywords: Biochemistry
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  • 56
    Publication Date: 2017-10-20
    Description: Dopamine receptors are implicated in the pathogenesis and treatment of nearly every neuropsychiatric disorder. Although thousands of drugs interact with these receptors, our molecular understanding of dopaminergic drug selectivity and design remains clouded. To illuminate dopamine receptor structure, function, and ligand recognition, we determined crystal structures of the D 4 dopamine receptor in its inactive state bound to the antipsychotic drug nemonapride, with resolutions up to 1.95 angstroms. These structures suggest a mechanism for the control of constitutive signaling, and their unusually high resolution enabled a structure-based campaign for new agonists of the D 4 dopamine receptor. The ability to efficiently exploit structure for specific probe discovery—rapidly moving from elucidating receptor structure to discovering previously unrecognized, selective agonists—testifies to the power of structure-based approaches.
    Keywords: Biochemistry
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  • 57
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-10-20
    Description: Lipoyl synthase (LipA) catalyzes the last step in the biosynthesis of the lipoyl cofactor, which is the attachment of two sulfhydryl groups to C6 and C8 of a pendant octanoyl chain. The appended sulfur atoms derive from an auxiliary [4Fe-4S] cluster on the protein that is degraded during turnover, limiting LipA to one turnover in vitro. We found that the Escherichia coli iron-sulfur (Fe-S) cluster carrier protein NfuA efficiently reconstitutes the auxiliary cluster during LipA catalysis in a step that is not rate-limiting. We also found evidence for a second pathway for cluster regeneration involving the E. coli protein IscU. These results show that enzymes that degrade their Fe-S clusters as a sulfur source can nonetheless act catalytically. Our results also explain why patients with NFU1 gene deletions exhibit phenotypes that are indicative of lipoyl cofactor deficiencies.
    Keywords: Biochemistry
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  • 58
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-12-08
    Keywords: Biochemistry
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  • 59
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-12-08
    Keywords: Biochemistry
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  • 60
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-12-08
    Keywords: Biochemistry
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  • 61
    Publication Date: 2017-12-15
    Description: Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with l -amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of l - and d -amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods.
    Keywords: Biochemistry
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  • 62
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-12-08
    Description: Methylphosphonate synthase (MPnS) produces methylphosphonate, a metabolic precursor to methane in the upper ocean. Here, we determine a 2.35-angstrom resolution structure of MPnS and discover that it has an unusual 2-histidine-1-glutamine iron-coordinating triad. We further solve the structure of a related enzyme, hydroxyethylphosphonate dioxygenase from Streptomyces albus ( Sa HEPD), and find that it displays the same motif. Sa HEPD can be converted into an MPnS by mutation of glutamine-adjacent residues, identifying the molecular requirements for methylphosphonate synthesis. Using these sequence markers, we find numerous putative MPnSs in marine microbiomes and confirm that MPnS is present in the abundant Pelagibacter ubique. The ubiquity of MPnS-containing microbes supports the proposal that methylphosphonate is a source of methane in the upper, aerobic ocean, where phosphorus-starved microbes catabolize methylphosphonate for its phosphorus.
    Keywords: Biochemistry
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  • 63
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-12-08
    Keywords: Biochemistry
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  • 64
    Publication Date: 2017-12-08
    Description: Plant RuBisCo, a complex of eight large and eight small subunits, catalyzes the fixation of CO 2 in photosynthesis. The low catalytic efficiency of RuBisCo provides strong motivation to reengineer the enzyme with the goal of increasing crop yields. However, genetic manipulation has been hampered by the failure to express plant RuBisCo in a bacterial host. We achieved the functional expression of Arabidopsis thaliana RuBisCo in Escherichia coli by coexpressing multiple chloroplast chaperones. These include the chaperonins Cpn60/Cpn20, RuBisCo accumulation factors 1 and 2, RbcX, and bundle-sheath defective-2 (BSD2). Our structural and functional analysis revealed the role of BSD2 in stabilizing an end-state assembly intermediate of eight RuBisCo large subunits until the small subunits become available. The ability to produce plant RuBisCo recombinantly will facilitate efforts to improve the enzyme through mutagenesis.
    Keywords: Biochemistry
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  • 65
    Publication Date: 2017-12-08
    Description: The spliceosome undergoes dramatic changes in a splicing cycle. Structures of B, B act , C, C*, and intron lariat spliceosome complexes revealed mechanisms of 5'–splice site (ss) recognition, branching, and intron release, but lacked information on 3'-ss recognition, exon ligation, and exon release. Here we report a cryo–electron microscopy structure of the postcatalytic P complex at 3.3-angstrom resolution, revealing that the 3' ss is mainly recognized through non–Watson-Crick base pairing with the 5' ss and branch point. Furthermore, one or more unidentified proteins become stably associated with the P complex, securing the 3' exon and potentially regulating activity of the helicase Prp22. Prp22 binds nucleotides 15 to 21 in the 3' exon, enabling it to pull the intron-exon or ligated exons in a 3' to 5' direction to achieve 3'-ss proofreading or exon release, respectively.
    Keywords: Biochemistry
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  • 66
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-12-15
    Keywords: Biochemistry
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  • 67
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-07-14
    Keywords: Biochemistry
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  • 68
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-07-14
    Keywords: Biochemistry
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  • 69
    Publication Date: 2017-07-14
    Description: Proteins fold into unique native structures stabilized by thousands of weak interactions that collectively overcome the entropic cost of folding. Although these forces are "encoded" in the thousands of known protein structures, "decoding" them is challenging because of the complexity of natural proteins that have evolved for function, not stability. We combined computational protein design, next-generation gene synthesis, and a high-throughput protease susceptibility assay to measure folding and stability for more than 15,000 de novo designed miniproteins, 1000 natural proteins, 10,000 point mutants, and 30,000 negative control sequences. This analysis identified more than 2500 stable designed proteins in four basic folds—a number sufficient to enable us to systematically examine how sequence determines folding and stability in uncharted protein space. Iteration between design and experiment increased the design success rate from 6% to 47%, produced stable proteins unlike those found in nature for topologies where design was initially unsuccessful, and revealed subtle contributions to stability as designs became increasingly optimized. Our approach achieves the long-standing goal of a tight feedback cycle between computation and experiment and has the potential to transform computational protein design into a data-driven science.
    Keywords: Biochemistry
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  • 70
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-07-21
    Keywords: Biochemistry
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  • 71
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-05-26
    Keywords: Biochemistry
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  • 72
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-11-10
    Keywords: Biochemistry
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  • 73
    Publication Date: 2017-11-10
    Description: The lysosome degrades and recycles macromolecules, signals to the cytosol and nucleus, and is implicated in many diseases. Here, we describe a method for the rapid isolation of mammalian lysosomes and use it to quantitatively profile lysosomal metabolites under various cell states. Under nutrient-replete conditions, many lysosomal amino acids are in rapid exchange with those in the cytosol. Loss of lysosomal acidification through inhibition of the vacuolar H + –adenosine triphosphatase (V-ATPase) increased the luminal concentrations of most metabolites but had no effect on those of the majority of essential amino acids. Instead, nutrient starvation regulates the lysosomal concentrations of these amino acids, an effect we traced to regulation of the mechanistic target of rapamycin (mTOR) pathway. Inhibition of mTOR strongly reduced the lysosomal efflux of most essential amino acids, converting the lysosome into a cellular depot for them. These results reveal the dynamic nature of lysosomal metabolites and that V-ATPase- and mTOR-dependent mechanisms exist for controlling lysosomal amino acid efflux.
    Keywords: Biochemistry
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  • 74
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-10-20
    Keywords: Biochemistry
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  • 75
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-01-20
    Description: Enzymes provide the necessary impetus for chemical reactions to occur at a rate that can support biological life. They do so by forming a unique enzyme-substrate complex and thus lowering the energy required for a substrate to convert to a product. Numerous approaches have been used for more than 50 years to unravel the mechanisms of enzyme-mediated catalysis (1). Initial kinetic experiments helped to ascertain substrate specificity. Spectroscopic data have shown that enzymes are not static, and more recently, atomic-resolution nuclear magnetic resonance (NMR) data have revealed the extent and duration of the structural fluctuations (2–4). On page 262 of this issue, Kim et al. (5) use structural and computational methods to provide evidence for the crucial roles of protein dynamics and water in enzyme catalysis. Authors: Tamjeed Saleh, Charalampos G. Kalodimos
    Keywords: Biochemistry
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  • 76
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-01-27
    Description: Polynitrogens have the potential for ultrahigh-performing explosives or propellants because singly or doubly bonded polynitrogens can decompose to triply bonded dinitrogen (N2) with an extraordinarily large energy release. The large energy content and relatively low activation energy toward decomposition makes the synthesis of a stable polynitrogen allotrope an extraordinary challenge. Many elements exist in different forms (allotropes)—for example, carbon can exist as graphite, diamond, buckyballs, or graphene. However, no stable neutral allotropes are known for nitrogen, and only two stable homonuclear polynitrogen ions had been isolated until now—namely, the N3− anion (1) and the N5+ cation (2). On page 374 of this issue, Zhang et al. (3) report the synthesis and characterization of the first stable salt of the cyclo-N5− anion, only the third stable homonuclear polynitrogen ion ever isolated. Author: Karl O. Christe
    Keywords: Inorganic Chemistry
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  • 77
    Electronic Resource
    Electronic Resource
    Springer
    Queueing systems 27 (1997), S. 205-226 
    ISSN: 1572-9443
    Keywords: multiclass queueing networks ; ergodicity ; stability ; performance analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract We develop the use of piecewise linear test functions for the analysis of stability of multiclass queueing networks and their associated fluid limit models. It is found that if an associated LP admits a positive solution, then a Lyapunov function exists. This implies that the fluid limit model is stable and hence that the network model is positive Harris recurrent with a finite polynomial moment. Also, it is found that if a particular LP admits a solution, then the network model is transient.
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  • 78
    Electronic Resource
    Electronic Resource
    Springer
    Queueing systems 26 (1997), S. 343-363 
    ISSN: 1572-9443
    Keywords: retrial queues ; stability ; ergodicity ; renovation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract We consider the following Type of problems. Calls arrive at a queue of capacity K (which is called the primary queue), and attempt to get served by a single server. If upon arrival, the queue is full and the server is busy, the new arriving call moves into an infinite capacity orbit, from which it makes new attempts to reach the primary queue, until it finds it non-full (or it finds the server idle). If the queue is not full upon arrival, then the call (customer) waits in line, and will be served according to the FIFO order. If λ is the arrival rate (average number per time unit) of calls and μ is one over the expected service time in the facility, it is well known that μ 〉 λ is not always sufficient for stability. The aim of this paper is to provide general conditions under which it is a sufficient condition. In particular, (i) we derive conditions for Harris ergodicity and obtain bounds for the rate of convergence to the steady state and large deviations results, in the case that the inter-arrival times, retrial times and service times are independent i.i.d. sequences and the retrial times are exponentially distributed; (ii) we establish conditions for strong coupling convergence to a stationary regime when either service times are general stationary ergodic (no independence assumption), and inter-arrival and retrial times are i.i.d. exponentially distributed; or when inter-arrival times are general stationary ergodic, and service and retrial times are i.i.d. exponentially distributed; (iii) we obtain conditions for the existence of uniform exponential bounds of the queue length process under some rather broad conditions on the retrial process. We finally present conditions for boundedness in distribution for the case of nonpatient (or non persistent) customers.
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  • 79
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    Archive of applied mechanics 67 (1997), S. 447-456 
    ISSN: 1432-0681
    Keywords: Key words rotation ; stability ; energy criterion ; variational analysis ; functional analysis ; eigenvalue problem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Summary Stability of a heavy rotating rod with a variable cross section is studied by energy method. Bifurcation points for the system of equilibrium equations are analyzed. It is shown that for the case when the rotation speed exceeds the critical one, the trivial solution ceases to be the minimizer of the potential energy, so that rod loses stability, according to the energy criteria. Also, a new estimate of the maximal rod deflection in the post-critical state is obtained.
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    Journal of intelligent and robotic systems 20 (1997), S. 131-155 
    ISSN: 1573-0409
    Keywords: robot adaptive control ; basis function-like networks ; stability ; discrete variable structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Stable neural network-based sampled-data indirect and direct adaptivecontrol approaches, which are the integration of a neural network (NN)approach and the adaptive implementation of the discrete variable structurecontrol, are developed in this paper for the trajectory tracking control ofa robot arm with unknown nonlinear dynamics. The robot arm is assumed tohave an upper and lower bound of its inertia matrix norm and its states areavailable for measurement. The discrete variable structure control servestwo purposes, i.e., one is to force the system states to be within the stateregion in which neural networks are used when the system goes out of neuralcontrol; and the other is to improve the tracking performance within the NNapproximation region. Main theory results for designing stable neuralnetwork-based sampled data indirect and direct adaptive controllers aregiven, and the extension of the proposed control approaches to the compositeadaptive control of a flexible-link robot is discussed. Finally, theeffectiveness of the proposed control approaches is illustrated throughsimulation studies.
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    Journal of intelligent and robotic systems 19 (1997), S. 411-436 
    ISSN: 1573-0409
    Keywords: assembly planning ; stability ; robot ; forward ; operations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The paper presents an approach to sequence planning consisting in determining assembly sequences defined in terms of mating and non-mating operations and based on a dynamic expansion of the assembly tree obtained using a knowledge base management system. The planner considers the case of a single-robot assembly workcell. The use of stability and the detailed definition of sequences also by means of several non-mating operations are shown to be powerful instruments in the control of the tree expansion. Forward assembly planning has been chosen, in order to minimize the number of stability checks. Backtracking is avoided by combining precedence relations and stability analysis. Hard and soft constrains are introduced to drive the tree expansion. Hard constraints are precedence relations and stability analysis. All operations are associated to costs, which are used as soft constraints. The operation based approach enables one to manage even non-mating operations and to easily overcome the linearity constraint. Costs enable the planner to manage the association among tools and components. The first section of the paper concerns Stability Analysis that is subdivided into Static and Dynamic Stability Analysis. The former is mainly involved in analyzing gravity effects; the latter is mainly involved in evaluate inertia effects due to manipulation. Stability Analysis is implemented in a simplified form. Fundamental assumptions are: no rotational equilibrium condition is considered; for each reaction force only direction and versus, but not magnitude, are considered; friction is neglected. The second section discusses the structure of the planner and its implementation. The planner is a rule based system. Forward chaining and hypothetical reasoning are the inference strategies used. The knowledge base and the data base of the system are presented and the advantages obtained using a rule based system are discussed. The third section shows two planning examples, showing the performance of the system in a simple case and in an industrial test case, the assembly of a microwave branching filter composed of 26 components.
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    Acta mechanica Sinica 13 (1997), S. 366-376 
    ISSN: 1614-3116
    Keywords: vibro-impact ; stability ; multiplicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The coexisting periodic impacting motions and their multiplicity of a kind of dual component systems under harmonic excitation are analytically derived. The stability condition of a periodic impacting motion is given by analyzing the propagation of small, arbitrary perturbation from that motion. In numerical simulations, the periodic impacting motions are classified according to the system states before and after an impact. The numerical results show that there exist many types of vibro-impacts and the bifurcation of periodic vibro-impacts is not smooth.
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    Numerical algorithms 14 (1997), S. 343-359 
    ISSN: 1572-9265
    Keywords: progressive interpolation ; stability ; spline ; shape parameters ; geometric continuity ; 41A05 ; 41A15 ; 65D05 ; 65D07
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Mathematics
    Notes: Abstract In this paper, we study several interpolating and smoothing methods for data which are known “progressively”. The algorithms proposed are governed by recurrence relations and our principal goal is to study their stability. A recurrence relation will be said stable if the spectral radius of the associated matrix is less than one. The iteration matrices depend on shape parameters which come either from the connection at the knots, or from the nature of the interpolant between two knots. We obtain various stability domains. Moving the parameters inside these domains leads to interesting shape effects.
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    Journal of scientific computing 12 (1997), S. 361-369 
    ISSN: 1573-7691
    Keywords: Alternating-direction implicit ; difference scheme ; stability ; convergence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract A new alternating-direction implicit (ADI) scheme for solving three-dimensional parabolic differential equations has been developed based on the idea of regularized difference scheme. It is unconditionally stable and second-order accurate. Further, it overcomes the drawback of the Douglas scheme and is to be very well to simulate fast transient phenomena and to efficiently capture steady state solutions of parabolic differential equations. Numerical example is illustrated.
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    Journal of scientific computing 12 (1997), S. 215-231 
    ISSN: 1573-7691
    Keywords: Transport models ; shallow water ; splitting methods ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract We investigate the use of splitting methods for the numerical integration of three-dimensional transport-chemistry models. In particular, we investigate various possibilities for the time discretization that can take advantage of the parallelization and vectorization facilities offered by multi-processor vector computers. To suppress wiggles in the numerical solution, we use third-order, upwind-biased discretization of the advection terms, resulting in a five-point coupling in each direction. As an alternative to the usual splitting functions, such as co-ordinate splitting or operator splitting, we consider a splitting function that is based on a three-coloured hopscotch-type splitting in the horizontal direction, whereas full coupling is retained in the vertical direction. Advantages of this splitting function are the easy application of domain decomposition techniques and unconditional stability in the vertical, which is an important property for transport in shallow water. The splitting method is obtained by combining the hopscotch-type splitting function with various second-order splitting formulae from the literature. Although some of the resulting methods are highly accurate, their stability behaviour (due to horizontal advection) is quite poor. Therefore we also discuss several new splitting formulae with the aim to improve the stability characteristics. It turns out that this is possible indeed, but the price to pay is a reduction of the accuracy. Therefore, such methods are to be preferred if accuracy is less crucial than stability; such a situation is frequently encountered in solving transport problems. As part of the project TRUST (Transport and Reactions Unified by Splitting Techniques), preliminary versions of the schemes are implemented on the Cray C98 4256 computer and are available for benchmarking.
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    Journal of scientific computing 12 (1997), S. 353-360 
    ISSN: 1573-7691
    Keywords: Alternating-direction implicit ; difference scheme ; stability ; convergence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract A generalized Peaceman–Rachford alternating-direction implicit (ADI) scheme for solving two-dimensional parabolic differential equations has been developed based on the idea of regularized difference scheme. It is to be very well to simulate fast transient phenomena and to efficiently capture steady state solutions of parabolic differential equations. Numerical example is illustrated.
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    Journal of dynamical and control systems 3 (1997), S. 291-319 
    ISSN: 1573-8698
    Keywords: 34D15 ; 34E15 ; 34A60 ; 93C73 ; 93D20 ; 49N99 ; Singular perturbation ; differential inclusion ; control systems ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract We study the continuity properties of the bundle of solutions to a differential inclusion subject to a singular perturbation, i.e., with respect to a scalar parameter ɛ multiplying a part of the derivatives. We give conditions under which every solution of the singularly perturbed inclusion is close, in a certain sense and for a sufficiently small ɛ, to a solution of the degenerate inclusion obtained for ɛ=0. These conditions include both stability and structural requirements (the later having no counterpart in the case of a differential equation). The main result obtained generalizes the well-known Tikhonov theorem for singularly perturbed differential equations.
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    Colloid & polymer science 275 (1997), S. 155-161 
    ISSN: 1435-1536
    Keywords: Key words HCO-10 ; vesicles ; encapsulation ; stability ; solubilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract  The characteristics of poly(oxyethylene) hydrogenated caster oil ether (HCO-10) vesicles were studied for the standpoints of encapsulation efficiency, stability, solubilization and permeability or barrier efficiency. The vesicles of 5% HCO-10 had 6.24% of calcein-entrapment efficiency and 240 nm of mean diameter. The stability of HCO-10 vesicle suspensions was dependent on their concentrations. In the vesicle suspensions of 10% HCO-10 or more, both the size of the vesicles and the fluidity of the suspensions obviously varied with incubation time, indicating that a flocculation occurred; whereas, the vesicle suspension of 5% HCO-10 was relatively stable. The solubilization process of HCO-10 vesicles by SDS was similar to that of EggPC liposomes. The rate constants for permeation of Cl ion and calcein were 2.46×10-3 s-1 and 5.79×10-5 s-1, respectively, suggesting that HCO-10 vesicles possessed some barrier potential for Cl ion and calcein although they were smaller than those of liposomes. Furthermore, the efflux of the solute such as calcein from HCO-10 vesicles was maximum at 37 °C, where the vesicle membrane was presumably destabilized by dehydration of EOs in HCO-10 molecules.
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    Colloid & polymer science 105 (1997), S. 38-40 
    ISSN: 1435-1536
    Keywords: α-haematite hydrosols ; stability ; urea ; ionic adsorption sequence ; water structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The effect of urea on the stability of α-haematite hydrosols in the presence of various monovalent ions was studied on each side of the pzc (pH 8.2) by measurements of the critical coagulation concentration (CCC) of the hydrosol. It was observed that for pHs lower than the pzc, the effect of urea depends strongly on the nature of coagulating ion and on the pH:The CCC values of IO 3 − increases with urea concentrations but those of ClO 4 − and Cl− decreases. For pHs higher than the pzc, an inversion of the cationic adsorption sequence was observed. This behavior is in a good agreement with the well-known action of urea on the structure of water and also with the general property of the α-haematite water interface.
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    Journal of elasticity 48 (1997), S. 218-239 
    ISSN: 1573-2681
    Keywords: stability ; nonlinear elasticity ; Mooney-Rivlin material ; incompressible material ; thick-walled tube
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The problem of instability of a hyperelastic, thick-walled cylindrical tube was first studied by Wilkes [1] in 1955. The solution was formulated within the framework of the theory of small deformations superimposed on large homogeneous deformations for the general class of incompressible, isotropic materials; and results for axially symmetrical buckling were obtained for the neo-Hookean material. The solution involves a certain quadratic equation whose characteristic roots depend on the material response functions. For the neo-Hookean material these roots always are positive. In fact, here we show for the more general Mooney–Rivlin material that these roots always are positive, provided the empirical inequalities hold. In a recent study [2] of this problem for a class of internally constrained compressible materials, it is observed that these characteristic roots may be real-valued, pure imaginary, or complex-valued. The similarity of the analytical structure of the two problems, however, is most striking; and this similarity leads one to question possible complex-valued solutions for the incompressible case. Some remarks on this issue will be presented and some new results will be reported, including additional results for both the neo-Hookean and Mooney–Rivlin materials.
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    Dynamics and control 7 (1997), S. 263-268 
    ISSN: 1573-8450
    Keywords: Structural control ; active control ; stability ; instability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract In a recent paper leit one of the authors noted, without presenting aproof, that appropriate variation of the stiffness coefficient in amass-spring-damper system leads to increase of the system energy during acycle of the motion. Some have expressed doubt concerning the validity ofthis claim which implies that a damped simple oscillator can be destabilizedby varying the spring constant. It is the purpose of this note to present aproof.
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    International Journal for Numerical Methods in Fluids 25 (1997), S. 739-748 
    ISSN: 0271-2091
    Keywords: incomplete LU preconditioning ; skyline format ; stability ; approximate inverse ; lid-driven cavity ; Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Incomplete LU factorizations are among the most effective preconditioners for solving general large, sparse linear systems arising from practical engineering problems. This paper shows how an ILU factorization may be easily computed in sparse skyline storage format, as opposed to traditional row-by-row schemes. This organization of the factorization has many advantages, including its amenability when the original matrix is in skyline format, the ability to dynamically monitor the stability of the factorization and the fact that factorizations may be produced with symmetric structure. Numerical results are presented for Galerkin finite element matrices arising from the standard square lid-driven cavity problem. © 1997 John Wiley & Sons, Ltd.
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    International Journal for Numerical Methods in Fluids 25 (1997), S. 547-566 
    ISSN: 0271-2091
    Keywords: parallel computing ; implicit scheme ; multidomain computations ; stability ; turbulent flow ; duct flow ; Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: A multidomain method for the solution of elliptic CFD problems with an ADI scheme is described. Two methods of treatment of internal boundary conditions for ADI functions are discussed, namely an explicit and a semi-implicit method. Stability conditions for the proposed methods are derived theoretically. The semi-implicit scheme is more stable than the explicit scheme, leading to improved numerical efficiency for multidomain computations. Numerical computations for a linear convection-diffusion equation, for buoyancy-driven recirculating flow in a square cavity and for turbulent flow in a square duct confirmed the theoretical results. Computer runs of the multidomain code in a distributed memory multiprocessor system were successful and efficient and produced reliable results. © 1997 John Wiley & Sons, Ltd.
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