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.

Many Neglected Tropical Diseases (NTDs) have recently been subject of increased focus, particularly with relation to high-throughput screening (HTS) initiatives. These vital endeavours largely rely of two approaches, in vitro target-directed screening using biochemical assays or cell-based screening which takes no account of the target or targets being hit. Despite their successes both of these approaches have limitations; for example, the production of soluble protein and a lack of cellular context or the problems and expense of parasite cell culture. In addition, both can be challenging to miniaturize for ultra (u)HTS and expensive to utilize. Yeast-based systems offer a cost-effective approach to study and screen protein targets in a direct-directed manner within a eukaryotic cellular context. In this review, we examine the utility and limitations of yeast cell-based, target-directed screening. In particular we focus on the currently under-explored possibility of using such formats in uHTS screening campaigns for NTDs.

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.

Epitaxial SiGe/Si layers are being extensively investigated for use in base regions of high-speed heterojunction bipolar-transistors (HBTs). Extended defects can be formed in SiGe/Si layers by ion-implantation. Defects, once formed in the layers, can negatively impact electrical performance and also future reliability of the HBTs. The present study investigates the interaction between selective-implant damage and strained SiGe/Si layers of sub-critical thickness. Implant-damage is observed to form dislocation-sources at the edges of implanted regions in SiGe/Si heterolayers. The dislocation sources produce glide dislocation loops. Segments of these loops glide down to SiGe/Si interfaces causing misfit dislocations to arise at interfaces in the heterolayers. Misfitdislocations are formed in directions parallel to and perpendicular to the <110> edge of the implanted region. Dislocations propagate out to a distance of ∼100-150 nm past the edge of the implant in the case of Si0.9Ge0.1/Si layers of sub-critical thickness. The origin and behavior of these defects is discussed.

Miniaturized thin film humidity sensors were fabricated using nanostructured materials deposited by an advanced technique known as glancing angle deposition (GLAD). These sensors exhibited extremely fast desorption response times of less than 40 ms to steplike changes in humidity. Multiple response time measurements for various initial humidities have shown that the sensors maintain their rapid response at all levels of humidity.

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.

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.