Using Singular Spectrum Analysis to obtain staffing level requirements in emergency units

Many operational research (OR) techniques use historical data to populate model input parameters. Although the majority of these models take into account stochastic variation of the inputs, they do not necessarily take into account seasonal variations and other stochastic effects that might arise. One of the major applications of OR lies within healthcare, where ever increasing pressure on healthcare systems is having major implications on those who plan the provision of such services. Coping with growing demand for healthcare, as well as the volatile nature of the number of arrivals at a healthcare facility makes modelling healthcare provision one of the most challenging fields of OR. This paper proposes the use of a relatively modern time series technique, Singular Spectrum Analysis (SSA), to improve existing algorithms that give required staffing levels. The methodology is demonstrated using data from a large teaching hospital's emergency unit. Using time dependent queueing theory, as well as SSA, staffing levels are obtained. The performance of our technique is analysed using a weighted mean square error measure, introduced in this paper.     

Plate-based diversity subset screening: an efficient paradigm for high throughput screening of a large screening file

The screening files of many large companies, including Pfizer, have grown considerably due to internal chemistry efforts, company mergers and acquisitions, external contracted synthesis, or compound purchase schemes. In order to screen the targets of interest in a cost-effective fashion, we devised an easy-to-assemble, plate-based diversity subset (PBDS) that represents almost the entire computed chemical space of the screening file whilst comprising only a fraction of the plates in the collection. In order to create this file, we developed new design principles for the quality assessment of screening plates: the Rule of 40 (Ro40) and a plate selection process that insured excellent coverage of both library chemistry and legacy chemistry space. This paper describes the rationale, design, construction, and performance of the PBDS, that has evolved into the standard paradigm for singleton (one compound per well) high-throughput screening in Pfizer since its introduction in 2006.     

Constant pH Molecular Dynamics Simulations of Nucleic Acids in Explicit Solvent

The nucleosides of adenine and cytosine have pKa values of 3.50 and 4.08, respectively, and are assumed to be unprotonated under physiological conditions. However, evidence from recent NMR and X-Ray crystallography studies has revealed the prevalence of protonated adenine and cytosine in RNA macromolecules. Such nucleotides with elevated pKa values may play a role in stabilizing RNA structure and participate in the mechanism of ribozyme catalysis. With the work presented here, we establish the framework and demonstrate the first constant pH MD simulations (CPHMD) for nucleic acids in explicit solvent in which the protonation state is coupled to the dynamical evolution of the RNA system via λ-dynamics. We adopt the new functional form λ(Nexp) for λ that was recently developed for Multi-Site λ-Dynamics (MSλD) and demonstrate good sampling characteristics in which rapid and frequent transitions between the protonated and unprotonated states at pH = pKa are achieved. Our calculated pKa values of simple nucleotides are in a good agreement with experimentally measured values, with a mean absolute error of 0.24 pKa units. This work demonstrates that CPHMD can be used as a powerful tool to investigate pH-dependent biological properties of RNA macromolecules.     

Expanding the scope of the asymmetric anti-aldol addition of chiral N-amino cyclic carbamate hydrazones

An asymmetric anti-aldol addition process of ketone-derived donors that is not limited by the structure of the ketone is described. This is achieved by merging the enantioselective α,α-bisalkylation of N-amino cyclic carbamate (ACC) hydrazones with the asymmetric anti-aldol addition of ACC hydrazones. The products of this process are obtained with essentially perfect stereoselectivity. Using this procedure it is possible to gain access to ketone-based anti-aldol addition products that are inaccessible in a controlled sense via direct aldol methods.     

Experimental evidence for supercontinuum generation by fission of higher-order solitons in photonic fibers

We report on an experimental study of supercontinuum generation in photonic crystal fibers with low-intensity femtosecond pulses, which provides evidence for a novel spectral broadening mechanism. The observed results agree with our theoretical calculations carried out without making the slowly varying envelope approximation. Peculiarities of the measured spectra and their theoretical explanation demonstrate that the reason for the white-light generation in photonic crystal fibers is fission of higher-order solitons into redshifted fundamental solitons and blueshifted nonsolitonic radiation.     

Prediction of a phase transition to a hydrogen bond ordered form of ice VI

Ice VI is a hydrogen bond disordered crystal over its known region of stability. In this work, we predict that ice VI will transform into a hydrogen bond ordered phase near 108 K, and have identified the likely low-temperature phase as ferroelectric (space group Cc) with an antiferroelectric structure (space group P2(1)2(1)2(1)) close by in energy. Electronic density functional theory calculations provide input to our calculations, which are extended to cells large enough for statistical simulations by using graph invariants. A significant decrease in the configurational entropy is predicted as hydrogen bonds exhibit partial order above the transition, provided that the hydrogen bonds can equilibrate on an experimental time scale. Conversely, partial disorder is predicted at temperatures below the transition. Although some evidence for ordering of ice VI has been observed in experiments, a low-temperature proton ordered phase has not been identified experimentally.     

Hydrogen-bond topology and the ice VII/VIII and ice Ih/XI proton-ordering phase transitions

The existence of an ice Ih/XI proton-ordering transition to a low-temperature ferroelectric phase has sparked considerable debate in the literature. Electronic density functional theory calculations, extended using graph invariants, confirm that a transition to a low-temperature ferroelectric phase should occur. The predicted transition at 98 K is in qualitative agreement with the observed transition at 72 K, and the low-temperature phase is the ferroelectric phase determined in diffraction experiments. The theoretical methods used to predict the phase transition are validated by comparing their prediction to the well-characterized ice VII/VIII proton-ordering transition.     

A hybrid active/passive exhaust noise control system for locomotives

A prototype hybrid system consisting of active and passive components for controlling far-field locomotive exhaust noise has been designed, assembled, and tested on a locomotive. The system consisted of a resistive passive silencer for controlling high-frequency broadband noise and a feedforward multiple-input, multiple-output active control system for suppressing low-frequency tonal noise. The active system used ten roof-mounted bandpass speaker enclosures with 2-12-in. speakers per enclosure as actuators, eight roof-mounted electret microphones as residual sensors, and an optical tachometer that sensed locomotive engine speed as a reference sensor. The system was installed on a passenger locomotive and tested in an operating rail yard. Details of the system are described and the near-field and far-field noise reductions are compared against the design goal.     

Selective mode excitation in hollow-core photonic crystal fiber

Modes are selectively excited by launching light through the cladding from the side into a hollow-core photonic crystal fiber. Measuring the total output power at the end of the fiber as a function of the angle of incidence of the exciting laser beam provides a powerful diagnostic for characterizing the cladding bandgap. Furthermore, various types of modes on either side of the bandgap are excited individually, and their nearfield images are obtained.