Towards molecular simulations that are transparent,reproducible, usable by others,and extensible (TRUE)

ABSTRACT

Systems composed of soft matter (e.g. liquids, polymers, foams, gels, colloids, and most biological materials) are ubiquitous in science and engineering, but molecular simulations of such systems pose particular computational challenges, requiring time and/or ensemble-averaged data to be collected over long simulation trajectories for property evaluation. Performing a molecular simulation of a soft matter system involves multiple steps, which have traditionally been performed by researchers in a ‘bespoke’ fashion, resulting in many published soft matter simulations not being reproducible based on the information provided in the publications. To address the issue of reproducibility and to provide tools for computational screening, we have been developing the open-source Molecular Simulation and Design Framework (MoSDeF) software suite. In this paper, we propose a set of principles to create Transparent, Reproducible, Usable by others, and Extensible (TRUE) molecular simulations. MoSDeF facilitates the publication and dissemination of TRUE simulations by automating many of the critical steps in molecular simulation, thus enhancing their reproducibilitya. We provide several examples of TRUE molecular simulations: All of the steps involved in creating, running and extracting properties from the simulations are distributed on open-source platforms (within MoSDeF and on GitHub), thus meeting the definition of TRUE simulations.     

Structure,conformation in aqueous solution and antimicrobial activity of ulvan extracted from green seaweed Ulva reticulata

The aim of this study is to elucidate the structure and investigate the antimicrobial activity of an ulvan obtained by water extraction from green seaweed Ulva reticulata collected at Nha Trang sea of Vietnam by using IR, NMR, SEC-MALLS and SAXS methods. The ulvan is composed of rhamnose, galactose, xylose, manose and glucose (mole ratio Rha: Gal: Xyl: Man: Glu = 1:0.12:0.1:0.06:0.03), uronic acid (22.5%) and sulphate groups (17.6%). Chemically structural determination showed that the ulvan mainly composed of disaccharide [→4)β-D-GlcA(1→4)α-L-Rha3S-(1→]. The results from SAXS indicated that ulvan under study has a rod-like bulky chain conformation. Ulvan from U. reticulata showed high antimicrobial activity, with inhibition zone diameter of 20 mm against Enterobacter cloace and 18 mm against Escherichia coli.     

Ultrahigh-efficiency power amplifier for space radar applications

This paper describes a broad-band switch mode power amplifier based on the indium phosphide (InP) double heterojunction bipolar transistor (DHBT) technology. The amplifier combines the alternative Class-E mode of operation with a harmonic termination technique that minimizes the insertion loss of matching circuitry to obtain ultrahigh-efficiency operation at X-band. For broad-band Class-E performance, the amplifiers output network employs a transmission line topology to achieve broad-band harmonic terminations while providing the optimal fundamental impedance to shape the output current and voltage waveforms of the device for maximum efficiency performance. As a result, 65% power-added efficiency (PAE) was achieved at 10 GHz. Over the frequency band of 9-11 GHz, the power amplifier achieved 49%-65% PAE, 18-22 dBm of output power, and 8-11 dB gain at 4 V supply. The reported power amplifier achieved what is believed to be the best PAE performance at 10 GHz and the widest bandwidth for a switch-mode design at X-band.     

Systematic IEEE rounding method for high-speed floating-point multipliers

For performance reasons, many high-speed floating-point multipliers today precompute multiple significand values (SVs) in advance. The final normalization and rounding steps are then performed by selecting the appropriate SV. While having speed advantages, this integrated rounding method complicates the development of the rounding logic significantly, hence, requiring a systematic rounding method. The systematic rounding method, presented in this paper, has three steps: 1) constructing a rounding table; 2) developing a prediction scheme; and 3) performing rounding digits selection (RDS). The rounding table lists all possible SVs that need to be precomputed. Prediction reduces the number of these SVs for efficient hardware implementation while RDS reduces the complexity of the rounding logic. Both prediction and RDS depend on the specifics of the hardware implementation. Two hardware implementations are described. The first one is modeled after that reported by Santoro et al. and the second improved one supports all IEEE rounding modes. Besides allowing systematic hardware optimization, this rounding method has the added advantage that verification and generalization are straightforward.     

Fleetamine (3-O-α-d-glucopyranosyl-swainsonine): the synthesis of a hypothetical inhibitor of endo-α-mannosidase

3-O-α-d-Glucopyranosyl-swainsonine was originally proposed¹⁷ as a potential inhibitor of the mammalian enzyme endo-α-mannosidase, but its synthesis has not been reported. Herein we report the total synthesis of this enigmatic compound, utilizing a halide-ion catalysed glycosylation of a swainsonine lactam with a glucosyl iodide donor as the key step. The resulting inhibitor was evaluated as an inhibitor of human endo-α-mannosidase, and as a ligand for bacterial orthologs from Bacteroides thetaiotaomicron and Bacteroides xylanisolvens, including active-centre variants, although no evidence for binding or inhibition was observed. The surprising lack of binding was rationalized by using structural alignment with an endo-α-mannosidase inhibitor complex, which identified deleterious interactions with the swainsonine piperidine ring and an essential active site residue.     

Gold nanoparticle-quantum dot-polystyrene microspheres as fluorescence resonance energy transfer probes for bioassays

The paper describes the development of highly sensitive particle-based fluorescence resonance energy transfer (FRET) probes that do not use molecular fluorophores as donors and acceptors. In these probes, CdSe/ZnS luminescent quantum dots (QDs) were capped with multiple histidine-containing peptides to increase their aqueous solubility while maintaining their high emission quantum yield and spectral properties. The peptide-modified QDs (QD-His) were covalently attached to carboxyl-modified polystyrene (PS) microspheres to form highly emitting PS microspheres (QD-PS). Gold nanoparticles (AuNPs) were then covalently attached to the QD-PS surface to form AuNP-QD-PS composite microspheres that were used as FRET probes. Attachment of AuNPs to QD-PS completely quenched the QD emission through FRET interactions. The emission of QD-PS was restored when the AuNPs were removed from the surface by thiol ligand displacement. The new AuNP-QD-PS FRET platform is simple to prepare and highly stable, and it opens many new possibilities for carrying out FRET assays on microparticle-based platforms and in microarrays. The versatility of these assays could be greatly increased by replacing the linkers between the QDs and AuNPs with ones that selectively respond to specific cleaving agents or enzymes.     

Rapid affinity purification of erythropoietin from biological samples using disposable monoliths

Identification of post-translational modifications of proteins in biological samples often requires access to preanalytical purification and concentration methods. In the purification step high or low molecular weight substances can be removed by size exclusion filters, and high abundant proteins can be removed, or low abundant proteins can be enriched, by specific capturing tools. In this paper is described the experience and results obtained with a recently emerged and easy-to-use affinity purification kit for enrichment of the low amounts of EPO found in urine and plasma specimens. The kit can be used as a pre-step in the EPO doping control procedure, as an alternative to the commonly used ultrafiltration, for detecting aberrantly glycosylated isoforms. The commercially available affinity purification kit contains small disposable anti-EPO monolith columns (6 μL volume, Ø7 mm, length 0.15 mm) together with all required buffers. A 24-channel vacuum manifold was used for simultaneous processing of samples. The column concentrated EPO from 20 mL urine down to 55 μL eluate with a concentration factor of 240 times, while roughly 99.7% of non-relevant urine proteins were removed. The recoveries of Neorecormon (epoetin beta), and the EPO analogues Aranesp and Mircera applied to buffer were high, 76%, 67% and 57%, respectively. The recovery of endogenous EPO from human urine was 65%. High recoveries were also obtained when purifying human, mouse and equine EPO from serum, and human EPO from cerebrospinal fluid. Evaluation with the accredited EPO doping control method based on isoelectric focusing (IEF) showed that the affinity purification procedure did not change the isoform distribution for rhEPO, Aranesp, Mircera or endogenous EPO. The kit should be particularly useful for applications in which it is essential to avoid carry-over effects, a problem commonly encountered with conventional particle-based affinity columns. The encouraging results with EPO propose that similar affinity monoliths, with the appropriate antibodies, should constitute useful tools for general applications in sample preparation, not only for doping control of EPO and other hormones such as growth hormone and insulin but also for the study of post-translational modifications of other low abundance proteins in biological and clinical research, and for sample preparation prior to in vitro diagnostics.     

Simplified ohmic and Schottky contact formation for field effecttransistors using the single layer integrated metal field effecttransistor (SLIMFET) process

A new III-V semiconductor device fabrication process for GaAs-based field effect transistors (FET) is presented which uses a single lithographic process and metal deposition step to form both the ohmic drain/source contacts and the Schottky gate contact concurrently. This single layer integrated metal FET (SLIMFET) process simplifies the fabrication process by eliminating an additional lithographic step for gate definition, a separate gate metallization step, and thermal annealing for ohmic contact formation. The SLIMFET process requires a FET structure which incorporates a compositionally graded In_xGa_1-xAs cap layer to form low resistance, nonalloyed ohmic contacts using standard Schottky metals. The SLIMFET process also uses a Si₃N₄ mask to provide selective removal of the InGaAs ohmic layers from the gate region prior to metallization without requiring an additional lithographic step. GaAs MESFET devices were fabricated using this new SLIMFET process which achieved DC and RF performance comparable to GaAs MESFET's fabricated by conventional methods     

A postdistortion receiver for mobile communications

The paper presents a postdistortion receiver, for possible future mobile communication systems, which can potentially increase both the spectral efficiency and the transmitter's power efficiency (especially important for portable units). Postdistortion is a technique, implemented at the base-station receiver, to compensate for AM-AM and AM-PM nonlinearities of a mobile transmitter's amplifier which, if uncompensated, would cause adjacent channel interference. A unique adaptation method is demonstrated to compensate for slow variations in the power amplifier's characteristics without an interruption for a training period. Various aspects of system performances, including SNR and convergence speed, have been simulated. The system performance in fading channel conditions is also considered. The simulation and measured results show that the postdistortion technique can improve the out-of-band emission by up to 20 dB; the corresponding increase in mobile transmitter power efficiency is approximately a factor of 10. The spectral efficiency is approximately increased by 20% with the postdistortion implementation     

Head-to-head vinyl polymers. VII. Hydrolysis of head-to-head poly(methyl acrylate)

Head-to-head (H–H) and head-to-tail (H–T) poly(methyl acrylate)s (PMAs) were hydrolyzed in a mixture of acetone and water (4:1 by volume) at 30°C by using various alkali hydroxides as catalysts. For comparison, the H–T copolymer with 26% H–H units, dimethyl succinate (DMS), dimethyl glutarate (DMG), and dimethyl adipate (DMA) as model compounds were also hydrolyzed. It was found that the hydrolyses of all PMAs proceeded autocatalytically; i.e., the rates increased as a function of the reaction time. Both the initial rate constant k₀ and the autoaccelerating effect observed markedly depended on the structures of polymer chains and they decreased with increasing of the H–H sequences. The molecular weights of either H—H or H—T PMA did not show remarkable changes in either k₀ value or accelerating effect. The k₀ values were almost independent of the kinds of bases and were calculated to be 0.06 and 0.18 L mol^?1 min^?1 for H–H and H–T PMA, respectively. On the other hand, the autoaccelerating effect decreased in the order NaOH ? KOH > LiOH > CsOH for H–H PMA and NaOH > LiOH > KOH > CsOH for H–T polymer. When the ratio of acetone to water increased, the k₀ value was found to decrease, whereas the accelerating effect increased. The results obtained are described and discussed.