Metabolic and structural properties of human obestatin {1-23} and two fragment peptides

Obestatin is a peptide produced in the oxyntic mucosa of the stomach and co-localizes with ghrelin on the periphery of pancreatic islets. Several studies demonstrate that obestatin reduces food and water intake, decreases body weight gain, inhibits gastrointestinal motility, and modulates glucose-induced insulin secretion. In this study we evaluated the acute metabolic effects of human obestatin {1-23} and fragment peptides {1-10} or {11-23} in high-fat fed mice, and then investigated their solution structure by NMR spectroscopy and molecular modelling. Obestatins {1-23} and {11-23} significantly reduced food intake (86% and 90% respectively) and lowered glucose responses to feeding, whilst leaving insulin responses unchanged. No metabolic changes could be detected following the administration of obestatin (1-10). In aqueous solution none of the obestatin peptides possessed secondary structural features. However, in a 2,2,2-trifluoroethanol (TFE-d(3))-H2O solvent mixture, the structure of obestatin {1-23} was characterized by an a-helix followed by a single turn helix conformation between residues Pro(4) and Gln(15) and His(19) and Ala(22) respectively. Obestatin {1-10} showed no structural components whereas {11-23} contained an a-helix between residues Val(14) and Ser(20) in a mixed solvent. These studies are the first to elucidate the structure of human obestatin and provide clear evidence that the observed a-helical structures are critical for in vivo activity. Future structure/function studies may facilitate the design of novel therapeutic agents based on the obestatin peptide structure. (C) 2010 Elsevier Inc. All rights reserved.

The Influence of Friction Stir Welding Process Idealization on Residual Stress and Distortion Predictions for Future Airframe Assembly Simulations

The ability to accurately predict residual stresses and resultant distortions is a key product from process assembly simulations. Assembly processes necessarily consider large structural components potentially making simulations computationally expensive. The objective herein is to develop greater understanding of the influence of friction stir welding process idealization on the prediction of residual stress and distortion and thus determine the minimum required modeling fidelity for future airframe assembly simulations. The combined computational and experimental results highlight the importance of accurately representing the welding forging force and process speed. In addition, the results emphasize that increased CPU simulation times are associated with representing the tool torque, while there is potentially only local increase in prediction fidelity.

Non-linear finite-element analysis of punching capacities of steel-concrete bridge deck slabs

Punching failure is the common failure mode in concrete bridge deck slabs when these structural components are subjected to local patch loads, such as tyre loads. Past research has shown that reinforced concrete slabs in girder–slab type bridges have a load-carrying capacity far greater than the ultimate static loads predicted by traditional design methods, because of the presence of compressive membrane action. However, due to the instability problems from punching failure, it is difficult to predict ultimate capacities accurately in numerical analyses. In order to overcome the instability problems, this paper establishes an efficient non-linear finite-element analysis using the commercial finite-element package Abaqus. In the non-linear finite-element analysis, stabilisation methods were adopted and failure criteria were established to predict the ultimate punching behaviour of deck slabs in composite steel–concrete bridges. The proposed non-linear finite-element analysis predictions showed a good correlation on punching capacities with experimental tests.

Functional analysis of the glycero-manno-heptose 7-phosphate kinase domain from the bifunctional HldE protein, which is involved in ADP-L-glycero-D-manno-heptose biosynthesis

The core oligosaccharide component of the lipopolysaccharide can be subdivided into inner and outer core regions. In Escherichia coli, the inner core consists of two 3-deoxy-d-manno-octulosonic acid and three glycero-manno-heptose residues. The HldE protein participates in the biosynthesis of ADP-glycero-manno-heptose precursors used in the assembly of the inner core. HldE comprises two functional domains: an N-terminal region with homology to the ribokinase superfamily (HldE1 domain) and a C-terminal region with homology to the cytidylyltransferase superfamily (HldE2 domain). We have employed the structure of the E. coli ribokinase as a template to model the HldE1 domain and predict critical amino acids required for enzyme activity. Mutation of these residues renders the protein inactive as determined in vivo by functional complementation analysis. However, these mutations did not affect the secondary or tertiary structure of purified HldE1, as judged by fluorescence spectroscopy and circular dichroism. Furthermore, in vivo coexpression of wild-type, chromosomally encoded HldE and mutant HldE1 proteins with amino acid substitutions in the predicted ATP binding site caused a dominant negative phenotype as revealed by increased bacterial sensitivity to novobiocin. Copurification experiments demonstrated that HldE and HldE1 form a complex in vivo. Gel filtration chromatography resulted in the detection of a dimer as the predominant form of the native HldE1 protein. Altogether, our data support the notions that the HldE functional unit is a dimer and that structural components present in each HldE1 monomer are required for enzymatic activity.

Stiffness Analysis and Experiment of a Novel 5-DoF Parallel Kinematic Machine Considering Gravitational Effects

In order to carry out high-precision machining of aerospace structural components with large size, thin wall and complex surface, this paper proposes a novel parallel kinematic machine (PKM) and formulates its semi-analytical theoretical stiffness model considering gravitational effects that is verified by stiffness experiments. From the viewpoint of topology structure, the novel PKM consists of two substructures in terms of the redundant and overconstrained parallel mechanisms that are connected by two interlinked revolute joints. The theoretical stiffness model of the novel PKM is established based upon the virtual work principle and deformation superposition principle after mapping the stiffness models of substructures from joint space to operated space by Jacobian matrices and considering the deformation contributions of interlinked revolute joints to two substructures. Meanwhile, the component gravities are treated as external payloads exerting on the end reference point of the novel PKM resorting to static equivalence principle. This approach is proved by comparing the theoretical stiffness values with experimental stiffness values in the same configurations, which also indicates equivalent gravity can be employed to describe the actual distributed gravities in an acceptable accuracy manner. Finally, on the basis of the verified theoretical stiffness model, the stiffness distributions of the novel PKM are illustrated and the contributions of component gravities to the stiffness of the novel PKM are discussed.

Silicon, the silver bullet for mitigating biotic and abiotic stress, and improving grain quality, in rice?

Adequate silicon fertilization greatly boosts rice yield and mitigates biotic and abiotic stress, and improves grain quality through lowering the content of cadmium and inorganic arsenic. This review on silicon dynamics in rice considers recent advances in our understanding of the role of silicon in rice, and the challenges of maintaining adequate silicon fertility within rice paddy systems. Silicon is increasingly considered as an element required for optimal plant performance, particularly in rice. Plants can survive with very low silicon under laboratory/glasshouse conditions, but this is highly artificial and, thus, silicon can be considered as essential for proper plant function in its environment. Silicon is incorporated into structural components of rice cell walls were it increases cell and tissue rigidity in the plant. Structural silicon provides physical protection to plants against microbial infection and insect attack as well as reducing the quality of the tissue to the predating organisms. The abiotic benefits are due to silicon's effect on overall organ strength. This helps protect against lodging, drought stress, high temperature (through efficient maintenance of transpiration), and photosynthesis by protecting against high UV. Furthermore, silicon also protects the plant from saline stress and against a range of toxic metal stresses (arsenic, cadmium, chromium, copper, nickel and zinc). Added to this, silicon application decreases grain concentrations of various human carcinogens, in particular arsenic, antimony and cadmium. As rice is efficient at stripping bioavailable silicon from the soil, recycling of silicon rich rice straw biomass or addition of inorganic silicon fertilizer, primarily obtained from iron and steel slag, needs careful management. Silicon in the soil may be lost if the silicon-cycle, traditionally achieved via composting of rice straw and returning it to the land, is being broken. As composting of rice straw and incorporation of composted or non-composted straw back to land are resource intensive activities, these activities are declining due to population shifts from the countryside to cities. Processes that accelerate rice straw composting, therefore, need to be identified to aid more efficient use of this resource. In addition, rice genetics may help address declining available silicon in paddy soils: for example by selecting for characteristics during breeding that lead to an increased ability of roots to access recalcitrant silicon sources from soil and/or via selection for traits that aid the maintenance of a high silicon status in shoots. Recent advances in understanding the genetic regulation of silicon uptake and transport by rice plants will aid these goals.

Multiple cutout optimization in composite plates using evolutionary structural optimization

The optimization of cutouts in composite plates was investigated by implementing a procedure known as Evolutionary Structural Optimization. Perforations were introduced into a finite element mesh of the plate from which one or more cutouts of a predetermined size were evolved. In the examples presented, plates were rejected from around each evolving cutout based on a predefined rejection criterion. The Limiting ply within each plate element around the cutout was determined based on the Tsai-Hill failure criterion. Finite element plates with values below the product of the average Tsai-Hill number and a rejection criterion were subsequently removed. This process was iterated until a steady state was reached and the rejection criterion was then incremented by an evolutionary rate and the above steps repeated until the desired cutout area was achieved. Various plates with differing lay-up and loading parameters were investigated to demonstrate the generality and robustness of this optimization procedure.

Experimental and Modelling Studies of the Thermodynamics and Kinetics of Phase and Structural Transformations in a Gamma TiAl-based Alloy

This work combines microscopy, synchrotron radiation X-ray diffraction, differential scanning calorimetry and thermodynamic calculations in the characterisation of phase transformation behaviour of a Ti–46Al–1.9Cr–3Nb alloy upon continuous heating at constant rates. It has been found that the Ti–46Al–1.9Cr–3Nb alloy after being forged at 1200 °C without further treatment has a duplex microstructure consisting of fine equiaxed and lamellar ? grains with a small amount of a2 plates and particles and about 1 wt.% B2 phase. Differential scanning calorimetry revealed reproducibly several thermal effects upon heating of the as-forged alloy. These thermal effects are related to the equilibration and homogenisation of the sample, change of phase ratios between a2, ? and B2 phases in particular the increase of B2 in respect to a2 and ?, and the following five phase transformations: a2 + ? + B2 a + ? + B2, a + ? + B2 a + ?, ? + a a, a a + ß, a + ß a + ß + L. The observation of these transformations by differential scanning calorimetry is largely in agreement with literature phase diagrams and thermodynamic calculations, though care is needed to consider the different alloy compositions. Kinetics of the ? + a a phase transformation in the Ti–46Al–1.9Cr–3Nb alloy has been quantitatively derived from the calorimetry data, giving phase compositions at any point during the transformation upon continuous heating.

Components of the peptidome and transcriptome persist in lin wa pi: the dried skin of the Heilongjiang brown frog Rana amurensis as used in Traditional Chinese Medicine

Although the ancient practice of traditional Chinese medicine (TCM) utilizes predominantly herbal ingredients, many of which are now the subject of intense scientific scrutiny, significant quantities of animal tissue-derived materials are also employed. Here we have used contemporary molecular techniques to study the material known as lin wa pi, the dried skin of the Heilongjiang brown frog, Rana amurensis, that is used commonly as an ingredient of many medicines, as a general tonic and as a topical antimicrobial/wound dressing. Using a simple technology that has been developed and validated over several years, we have demonstrated that components of both the skin granular gland peptidome and transcriptome persist in this material. Interrogation of the cDNA library constructed from the dried skin by entrapment and amplification of polyadenylated mRNA, using a "shotgun" primer approach and 3'-RACE, resulted in the cloning of cDNAs encoding the precursors of five putative antimicrobial peptides. Two (ranatuerin-2AMa and ranatuerin-2AMb) were obvious homologs of a previously described frog skin peptide family, whereas the remaining three were of sufficient structural novelty to be named amurins 1-3. Mature peptides were each identified in reverse phase HPLC fractions of boiling water extracts of skin and their structures confirmed by MS/MS fragmentation sequencing. Components of traditional Chinese medicines of animal tissue origin may thus contain biologically active peptides that survive the preparation procedures and that may contribute to therapeutic efficacy.

Flatworm nerve-muscle: structural and functional analysis

Platyhelminthes occupy a unique position in nerve-muscle evolution, being the most primitive of metazoan phyla. Essentially, their nervous system consists of an archaic brain and associated pairs of longitudinal nerve cords cross-linked as an orthogon by transverse commissures. Confocal imaging reveals that these central nervous system elements are in continuity with an array of peripheral nerve plexuses which innervate a well-differentiated grid work of somatic muscle as well as a complexity of myofibres associated with organs of attachment, feeding, and reproduction. Electrophysiological studies of flatworm muscles have exposed a diversity of voltage-activated ion channels that influence muscle contractile events. Neuronal cell types are mainly multi- and bi-polar and highly secretory in nature, producing a heterogeneity of vesicular inclusions whose contents have been identified cytochemically to include all three major types of cholinergic, aminergic, and peptidergic messenger molecules. A landmark discovery in flatworm neurobiology was the biochemical isolation and amino acid sequencing of two groups of native neuropeptides: neuropeptide F and FMRFamide-related peptides (FaRPs). Both families of neuropeptide are abundant and broadly distributed in platyhelminths, occurring in neuronal vesicles in representatives of all major flatworm taxa. Dual localization studies have revealed that peptidergic and cholinergic substances occupy neuronal sets separate from those of serotoninergic components. The physiological actions of neuronal messengers in flatworms are beginning to be established, and where examined, FaRPs and 5-HT are myoexcitatory, while cholinomimetic substances are generally inhibitory. There is immunocytochemical evidence that FaRPs and 5-HT have a regulatory role in the mechanism of egg assembly. Use of muscle strips and (or) muscle fibres from free-living and parasitic flatworms has provided baseline information to indicate that muscle responses to FaRPs are mediated by a G-protein-coupled receptor, and that the signal transduction pathway for contraction involves the second messengers cAMP and protein kinase C.

Towards hierarchical management of autonomic components: a case study

We address the issue of autonomic management in hierarchical component-based distributed systems. The long term aim is to provide a modelling framework for autonomic management in which QoS goals can be defined, plans for system adaptation described and proofs of achievement of goals by (sequences of) adaptations furnished. Here we present an early step on this path. We restrict our focus to skeleton-based systems in order to exploit their well-defined structure. The autonomic cycle is described using the Orc system orchestration language while the plans are presented as structural modifications together with associated costs and benefits. A case study is presented to illustrate the interaction of managers to maintain QoS goals for throughput under varying conditions of resource availability.

Rare-earth quinolinates: Infrared-emitting molecular materials with a rich structural chemistry

Near-infrared-emitting rare-earth chelates based on 8-hydroxyquinoline have appeared frequently in recent literature, because they are promising candidates for active components in near-infrared-luminescent optical devices, such as optical amplifiers, organic light-emitting diodes, .... Unfortunately, the absence of a full structural investigation of these rare-earth quinolinates is hampering the further development of rare-earth quinolinate based materials, because the luminescence output cannot be related to the structural properties. After an elaborate structural elucidation of the rare-earth quinolinate chemistry we can conclude that basically three types of structures can be formed, depending on the reaction conditions: tris complexes, corresponding to a 1:3 metal-to-ligand ratio, tetrakis complexes, corresponding to a 1:4 metal-to-ligand ratio, and trimeric complexes, with a 3:8 metal-to-ligand ratio. The intensity of the emitted near-infrared luminescence of the erbium(Ill) complexes is highest for the tetrakis complexes of the dihalogenated 8-hydroxyquinolinates.