Hydration of mononucleotides

The sequential addition of water molecules to protonated and deprotonated forms of the four mononucleotides dAMP, dCMP, dGMP, and dTMP was studied experimentally by equilibrium measurements using an electrospray mass spectrometer equipped with a drift cell and theoretically by computational methods including molecular modeling and density functional theory calculations. Experiments were carried out in positive and negative ion mode, and calculations included the protonated and deprotonated forms of the four nucleotides. For deprotonated anionic nucleotides the experimental enthalpies of hydration (DeltaH degrees n) were found to be similar for all four systems and varied between -10.1 and -11.5 kcal mol-1 for the first water molecule (n = 1) and -8.3 and -9.6 kcal mol-1 for additional water molecules (n = 2-4). Theory indicated that the first water molecule binds to the charge-carrying phosphate group. Simulations of deprotonated mononucleotides with four water molecules yielded a large number of structures with similar energies. In some of the structures all four water molecules cluster around the phosphate group, and in other structures the four water molecules each hydrate a different functional group of the nucleotide. These include the phosphate group, the deoxyribose hydroxyl group, and various functional groups on the nucleobases. Experimental DeltaH degrees 1 values for the protonated cationic mononucleotides ranged from -10.5 to -13.5 kcal mol-1 with more negative values (< or =-12 kcal mol-1) for dCMP, dGMP, and dTMP and the least negative value for dAMP. For n = 2-4 DeltaH degrees n values varied from -6.9 to -9.7 kcal/mol and were similar in value to the deprotonated nucleotides except for dAMP. Theory on the protonated nucleotides indicated that the first water molecule binds to the charge-carrying group for dCMP, dGMP, and dTMP. For protonated dAMP, on the other hand, the charge-carrying N3 group is well self-solvated by the phosphate group and not readily available for a hydrogen bond with the water molecule. The insight gained on nucleotide stabilization by individual water molecules is used to discuss the competition between hydration of individual nucleotides and Watson-Crick base pairing.     

The midpoint method for parallelization of particle simulations

The evaluation of interactions between nearby particles constitutes the majority of the computational workload involved in classical molecular dynamics (MD) simulations. In this paper, we introduce a new method for the parallelization of range-limited particle interactions that proves particularly suitable to MD applications. Because it applies not only to pairwise interactions but also to interactions involving three or more particles, the method can be used for evaluation of both nonbonded and bonded forces in a MD simulation. It requires less interprocessor data transfer than traditional spatial decomposition methods at all but the lowest levels of parallelism. It gains an additional practical advantage in certain commonly used interprocessor communication networks by distributing the communication burden more evenly across network links and by decreasing the associated latency. When used to parallelize MD, it further reduces communication requirements by allowing the computations associated with short-range nonbonded interactions, long-range electrostatics, bonded interactions, and particle migration to use much of the same communicated data. We also introduce certain variants of this method that can significantly improve the balance of computational load across processors.     

Design and characterization of arrayed waveguide gratings using ultra-low loss Si3N4 waveguides

Planar waveguides with ultra-low propagation loss are necessary for integrating optoelectronic systems that require long optical time delay or narrowband optical filters. In this paper, we review an ultra-low loss planar waveguide platform that uses thin (<150 nm) Si₃N₄ cores and thick (>8 μm) SiO₂ cladding layers. In particular, we discuss the performance of arrayed waveguide gratings (AWGs) fabricated with the platform. We propose the use of a practical design method that takes the statistical nature of worst-case crosstalk into account. We also demonstrate the measurement of amplitude and phase error distributions in an AWG using an optical backscatter reflectometer. We show that the waveguides have phase errors small enough to achieve AWG crosstalk below ?30 dB, while crosstalk below ?40 dB should also be possible with optimization of the component design.     

Exploring alternative routes to realising the benefits of simulation in healthcare

Discrete event simulation should offer numerous benefits in designing healthcare systems but the reality is often problematic. Healthcare modelling faces particular challenges: genuine, fundamental variations in practice and an opposition to any suggestion of standardisation from some professional groups. This paper compares the experiences of developing a new simulation in an Accident and Emergency (A&E) Department, a subsequent adaptation for modelling an outpatient clinic and applications of a generic A&E simulation. These studies provide examples of three distinct approaches to realising the potential benefits of simulation: the bespoke, the reuse and the generic route. Reuse has many advantages: it is relatively efficient in exploiting previous modelling experience, delivering timely results although providing scope for adaptations to local practice. Explicitly demonstrating this willingness to adapt to local conditions and engaging with stakeholders is particularly important in healthcare simulation.     

Quantitative fractionation of serum bilirubin species by reversed-phase high-performance liquid chromatography

A rapid high-performance liquid chromatographic method is described for separating and quantifying four bilirubin species present in serum: bilirubin, bilirubin monoglucuronide, bilirubin diglucuronide, and bilialbumin. Sample preparation consists of dilution with ascorbic acid and dimethylsulfoxide and filtration to remove solid materials. The diluted serum was injected directly onto a wide-pore (300 A) reversed-phase column and the bilirubin species eluted with a water-isopropanol gradient. Excellent agreement was found between the total bilirubin concentration measured by the high-performance liquid chromatographic method and a diazotized sulfanilic acid procedure.     

Maximal convex metrics on some classical metric spaces

It is proved that every convex, complete, two-point homogeneous metric for which small spheres are connected has maximal symmetry. This in turn implies that the standard metrics on the classical spaces of geometry are maximally symmetric.     

Fabrication and characteristics of double-fused vertical-cavity lasers

We discuss the fabrication process and characteristics of three consecutive runs of double-fused 1.5-m vertical-cavity lasers. We have measured light-current characteristics of over three hundred lasers with ten different diameters between 6 and 60 m and observe a yield of over 95%. The process and design improvements resulted in a low pulsed threshold current of 3 mA on a number of 6- and 8-m-diameter devices and threshold current density of 2 kA cm^–2 on 60-m-diameter devices at room temperature.     

Immobilized enzymes in chemical analysis

Immobilization of enzymes has proved to be useful in stabilizing them, in retrieving and reusing them, and in producing unstable or expensive reagents. Specific technologies have been developed for analytical applications of immobilized enzymes, including probes (e.g., enzyme electrodes) and reactors. The characteristics of these devices and their advantages and disadvantages will be presented.