Infrared (IR) spectroscopy is increasingly being used to probe the secondary structure of proteins, especially for high-concentration samples and biopharmaceuticals in complex formulation vehicles. However, the small path lengths required for aqueous protein transmission experiments, due to high water absorbance in the amide I region of the spectrum, means that the path length is not accurately known, so only the shape of the band is ever considered. This throws away a dimension of information. Attenuated total reflectance (ATR) IR spectroscopy is much easier to implement than transmission IR spectroscopy and, for a given instrument and sample, gives reproducible spectra. However, the ATR-absorbance spectrum varies with sample concentration and instrument configuration, and its wavenumber dependence differs significantly from that observed in transmission spectroscopy. In this paper, we determine, for the first time, how to transform water and aqueous protein ATR spectra into the corresponding transmission spectra with appropriate spectral shapes and intensities. The approach is illustrated by application to water, concanavalin A, haemoglobin and lysozyme. The transformation is only as good as the available water refractive index data. A hybrid of literature data provides the best results. The transformation also allows the angle of incidence of an ATR crystal to be determined. This opens the way to using both spectral shape and spectra intensity for protein structure fitting.

Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.

We analyze the optimal policy for the sequential selection of an alternating subsequence from a sequence of n independent observations from a continuous distribution F, and we prove a central limit theorem for the number of selections made by that policy. The proof exploits the backward recursion of dynamic programming and assembles a detailed understanding of the associated value functions and selection rules.

We consider sequential selection of an alternating subsequence from a sequence of independent, identically distributed, continuous random variables, and we determine the exact asymptotic behavior of an optimal sequentially selected subsequence. Moreover, we find (in a sense we make precise) that a person who is constrained to make sequential selections does only about 12 percent worse than a person who can make selections with full knowledge of the random sequence.

We consider the problem of selecting sequentially a unimodal subsequence from a sequence of independent identically distributed random variables, and we find that a person doing optimal sequential selection does so within a factor of the square root of two as well as a prophet who knows all of the random observations in advance of any selections. Our analysis applies in fact to selections of subsequences that have d+1 monotone blocks, and, by including the case d=0, our analysis also covers monotone subsequences.

We consider a simple model of sequential decisions made by a fusion agent that receives binary-passive reports from distributed sensors. The main result is an explicit formula for the probability of making a decision before a fixed budget is exhausted. These results depend on the relationship between a special ruin problem for a “lazy random walk” and a traditional biased walk.

Gravitational microlensing observations will lead to a census of planets that orbit stars of different populations. From 2008, ARTEMiS will provide an expert system that allows to adopt a three-step strategy of survey, follow-up and anomaly monitoring of gravitational microlensing events that is capable of detecting planets of Earth mass and below. The SIGNALMEN anomaly detector, an integral part, has already demonstrated its performance during a pilot season. Embedded into eSTAR, ARTEMiS serves as an open platform that links with existing microlensing campaigns. Real-time visualization of ongoing events along with an interpretation moreover allows to communicate “Science live to your home” to the general public.

Methods using gambling teams and martingales are developed and applied to find formulae for the expected value and the generating function of the waiting time to observation of an element of a finite collection of patterns in a sequence generated by a two-state Markov chain of first, or higher, order.

An optical-based humidity sensor with a sub-second response time was fabricated from a nanostructured titanium dioxide thin film. A refractive index profile designed to yield a narrow-bandpass optical interference filter was obtained through nanoscale porosity variations produced by glancing angle deposition (GLAD). Under varying humidity conditions the transmittance spectrum of the filter shifts due to effective index changes of the porous structure resulting from adsorption/desorption of water vapor. In the following we will show that this device is highly sensitive, exhibits minimal hysteresis, and is extremely fast. The adsorption and desorption response times were measured to be 270 ms and 160 ms, respectively.

Chemical treatments, when applied to nanostructured oxide thin films, can be used to generate added functionality in many devices. In this study, a nanostructured defect-mode optical filter was prepared by glancing angle deposition of titanium dioxide and functionalized with 3,3,3-trifluoropropyl-trichlorosilane to render the thin film insensitive to variable humidity conditions. Electrical characterization and contact angle measurements demonstrate that the hydrophilic thin film becomes hydrophobic when functionalized, and transmission measurements clearly show that the wavelength shift of the defect-mode becomes strongly inhibited for a wide range of humidity levels.