Dynameomics: design of a computational lab workflow and scientific data repository for protein simulations

Dynameomics is a project to investigate and catalog the native-state dynamics and thermal unfolding pathways of representatives of all protein folds using solvated molecular dynamics simulations, as described in the preceding paper. Here we introduce the design of the molecular dynamics data warehouse, a scalable, reliable repository that houses simulation data that vastly simplifies management and access. In the succeeding paper, we describe the development of a complementary multidimensional database. A single protein unfolding or native-state simulation can take weeks to months to complete, and produces gigabytes of coordinate and analysis data. Mining information from over 3000 completed simulations is complicated and time-consuming. Even the simplest queries involve writing intricate programs that must be built from low-level file system access primitives and include significant logic to correctly locate and parse data of interest. As a result, programs to answer questions that require data from hundreds of simulations are very difficult to write. Thus, organization and access to simulation data have been major obstacles to the discovery of new knowledge in the Dynameomics project. This repository is used internally and is the foundation of the Dynameomics portal site http://www.dynameomics.org. By organizing simulation data into a scalable, manageable and accessible form, we can begin to address substantial questions that move us closer to solving biomedical and bioengineering problems.     

Fed-batch optimization of recombinant <Emphasis Type="Italic">α</Emphasis>-amylase production by <Emphasis Type="Italic">Bacillus subtilis</Emphasis> using a modified Markov chain Monte Carlo technique

A modified Markov Chain Monte Carlo (MCMC) searching procedure was developed to search for an optimal set of decision variables and optimal feed rate trajectories for recombinant α-amylase expression by Bacillus subtilis ATCC 6051a. The bacterium also synthesizes proteases as undesirable products in fed-batch culture that need to be minimized. To maximize α-amylase productivity, a 14th-order fed-batch model was optimized by integrating Pontryagin’s maximum principle with the Luedeking-Piret equation. The number of iterations and simulations of the proposed searching procedure were statistically examined for accuracy and acceptability of the results. It can be concluded that the proposed searching procedure increased the parameter selection opportunity near the tail ends of redefined triangular distribution. By applying a modified MCMC searching procedure with 1,500 iterations, the predicted α-amylase productivity was improved by 18% in comparison with near-optimum experimental results. This productivity was 3.5% higher than predicted by conventional MCMC optimization.     

Modeling of mass transfer and thermal cracking during the coking of Athabasca residues

The kinetics of thermal cracking of films of vacuum residue from Athabasca bitumen in the temperature range of was modelled with liquid-phase mass transfer, reaction-dependent fluid properties, and coke formation by reaction of cracked products in the liquid phase. Previous investigations on the thermal cracking of vacuum residue in thin films showed that at low film thickness the coke yield was insensitive to the temperature and heating rate for thin films of bitumen. The coke yield increased with the thickness of the initial film, in the range from 20 to . At the same time, the viscosity of the reacting liquid increased rapidly with time, which would slow down the diffusion of products inside the film. This coupling of transport and reaction would enhance the formation of coke by increasing the rate of recombination reactions. The concept of intrinsic coke is used in a new kinetic model to account for the minimum observed coke formation in thin films. With increasing film thickness, the increasing yield of extrinsic coke is modelled through the change in fluid properties as a function of extent of reaction, which reduces the rate of diffusion in the reacting liquid phase. The model was able to properly account for the insensitivity of coke yield in thin films to reaction temperature and the dependence of coke yield on the thickness of the liquid film.     

Poly(amide‐imides): Wire Enamels with Excellent Thermal and Chemical Properties

Poly(amide‐imide) resins are versatile high‐performance polymers used as primary electrical insulation. They can be synthesized by three well‐established methods, of which only two are commercially exploited. Outstanding characteristics include high thermal performance, chemical and abrasion resistance, and low coefficient of friction. Other industries also rely on these same properties for use as coatings, extrusion resins and films. Recent developments are discussed and future trends/product offerings are reviewed. Developments include corona‐resistant enamels, self‐lubricated and high‐abrasion‐resistance coatings. The hybrid automobile industry offers opportunities for further innovations in primary electrical coatings.

     

Transfer of highly hydrophilic ions from water to nitrobenzene, studied by three-phase and thin-film modified electrodes

The study by voltammetry of hydrophilic ion transfers across the interface between an aqueous solution and an immiscible organic solvent is limited by the presence of supporting electrolytes in both phases. Such a study is impossible for ions having a higher affinity for water than ions of the electrolytes. Indirectly, methods based on modified solid electrodes can be used; these are obtained by the deposition of an organic phase containing a molecule having redox properties, the modified electrode being in contact with an aqueous solution of the appropriate electrolyte. The three-phase electrode is very convenient for that purpose. However, this experimental tool also has its own limitation, due mainly to the redox species produced in the organic phase. The oxidized, or reduced, form of the redox molecule must have a very low affinity for water, as otherwise its transfer masks that of the ion under study. Ferrocene is almost useless because of the affinity of the ferrocenium cation for water, decamethylferrocene being a better choice. The present work illustrates how the use of lutetium bisphthalocyanines widely expands the possibilities, as these molecular sandwich complexes can be reduced as well as oxidized, the products of the reactions having a very low affinity for water. This made the determination of the Gibbs energy possible for the transfers of highly hydrophilic ions from water to nitrobenzene: Cl(-) (40 kJ mol(-1)), F(-) (57 kJ mol(-1)), H2PO4(-) (64 kJ mol(-1)). Nothing being really known about the transfer of F(-) or H2PO4(-) from water to organic solvents, these are the first values ever published. H(+), OH(-), and HSO4(-) have also been studied, showing that these species, which have a poor affinity for nitrobenzene, are prone to association reactions with the reduced or oxidized forms of the lutetium bisphthalocyanine.     

Influence of torsion deformation on microstructure of cold-drawn pearlitic steel wire

A comparative microstructural analyse of cold-drawn pearlitic steel wires in as-drawn and after an additional torsion deformation states is presented in this paper. During torsion the temperature of the wire increases to attain 90 °C. Then the microstructure of wires is the result of different events effects, as initial drawing, temperature increase and torsion deformation. Individually or in association, both events influence the stress level and nature in ferrite and cementite lamellae, modify the kinetic of cementite decomposition and change the dislocation mobility in cementite and ferrite. Carbon atoms migration from cementite to ferrite is affected by these thermomechanical treatments inducing a modification of dislocation pinning by carbon atoms and lamellae interfaces. The phases’ determination and quantification, associated with the carbon content variation in each phase was investigated by Mössbauer spectroscopy. The evolution of the pearlitic steel wires microstructure will be discussed point-by-point, as a function of applied deformation nature.     

Effect of Oxime Ether Incorporation in Acyl Indole Derivatives on PPAR Subtype Selectivity

Compounds that simultaneously activate peroxisome proliferator‐activated receptor (PPAR) subtypes α and γ have the potential to effectively treat dyslipidemia and type 2 diabetes (T2D) in a single pharmaceutically active molecule. The frequently observed side effects of selective PPARγ agonists, such as edema and weight gain, were expected to be overcome by using additive PPARα activity, leading to dual PPARα/γ agonists with balanced activity for both subtypes. Herein we report the discovery, synthesis, and optimization of a new series of α‐ethoxyphenylpropionic acid bearing 5‐ or 6‐substituted indoles. The incorporation of oxime ethers on the carbonyl portion of the benzoyl group can bring the PPARα/γ potency ratio equal to or slightly greater than one, as is the case for compounds 20 c and 21 a . Compound 20 c shows high efficacy in an ob/ob mouse model of T2D and dyslipidemia, similar to that of rosiglitazone and tesaglitazar, but with a significant increase in body weight gain. In contrast, compound 21 a , less potent as a dual PPARα/γ activator than 20 c , showed an interesting pharmacological profile, as it elicits a decrease in body weight relative to reference compounds.     

Large-scale parallel arrays of silicon nanowires via block copolymer directed self-assembly

Extending the resolution and spatial proximity of lithographic patterning below critical dimensions of 20 nm remains a key challenge with very-large-scale integration, especially if the persistent scaling of silicon electronic devices is sustained. One approach, which relies upon the directed self-assembly of block copolymers by chemical-epitaxy, is capable of achieving high density 1?:?1 patterning with critical dimensions approaching 5 nm. Herein, we outline an integration-favourable strategy for fabricating high areal density arrays of aligned silicon nanowires by directed self-assembly of a PS-b-PMMA block copolymer nanopatterns with a L(0) (pitch) of 42 nm, on chemically pre-patterned surfaces. Parallel arrays (5 × 10(6) wires per cm) of uni-directional and isolated silicon nanowires on insulator substrates with critical dimension ranging from 15 to 19 nm were fabricated by using precision plasma etch processes; with each stage monitored by electron microscopy. This step-by-step approach provides detailed information on interfacial oxide formation at the device silicon layer, the polystyrene profile during plasma etching, final critical dimension uniformity and line edge roughness variation nanowire during processing. The resulting silicon-nanowire array devices exhibit Schottky-type behaviour and a clear field-effect. The measured values for resistivity and specific contact resistance were ((2.6 ± 1.2) × 10(5)Ωcm) and ((240 ± 80) Ωcm(2)) respectively. These values are typical for intrinsic (un-doped) silicon when contacted by high work function metal albeit counterintuitive as the resistivity of the starting wafer (～10 Ωcm) is 4 orders of magnitude lower. In essence, the nanowires are so small and consist of so few atoms, that statistically, at the original doping level each nanowire contains less than a single dopant atom and consequently exhibits the electrical behaviour of the un-doped host material. Moreover this indicates that the processing successfully avoided unintentional doping. Therefore our approach permits tuning of the device steps to contact the nanowires functionality through careful selection of the initial bulk starting material and/or by means of post processing steps e.g. thermal annealing of metal contacts to produce high performance devices. We envision that such a controllable process, combined with the precision patterning of the aligned block copolymer nanopatterns, could prolong the scaling of nanoelectronics and potentially enable the fabrication of dense, parallel arrays of multi-gate field effect transistors.