OBJECTIVES/SPECIFIC AIMS: Key factors causing irreproducibility of research include those related to inappropriate study design methodologies and statistical analysis. In modern statistical practice irreproducibility could arise due to statistical (false discoveries, p-hacking, overuse/misuse of p-values, low power, poor experimental design) and computational (data, code and software management) issues. These require understanding the processes and workflows practiced by an organization, and the development and use of metrics to quantify reproducibility. METHODS/STUDY POPULATION: Within the Foundation of Discovery – Population Health Research, Center for Clinical and Translational Science, University of Utah, we are undertaking a project to streamline the study design and statistical analysis workflows and processes. As a first step we met with key stakeholders to understand the current practices by eliciting example statistical projects, and then developed process information models for different types of statistical needs using Lucidchart. We then reviewed these with the Foundation’s leadership and the Standards Committee to come up with ideal workflows and model, and defined key measurement points (such as those around study design, analysis plan, final report, requirements for quality checks, and double coding) for assessing reproducibility. As next steps we are using our finding to embed analytical and infrastructural approaches within the statisticians’ workflows. This will include data and code dissemination platforms such as Box, Bitbucket, and GitHub, documentation platforms such as Confluence, and workflow tracking platforms such as Jira. These tools will simplify and automate the capture of communications as a statistician work through a project. Data-intensive process will use process-workflow management platforms such as Activiti, Pegasus, and Taverna. RESULTS/ANTICIPATED RESULTS: These strategies for sharing and publishing study protocols, data, code, and results across the spectrum, active collaboration with the research team, automation of key steps, along with decision support. DISCUSSION/SIGNIFICANCE OF IMPACT: This analysis of statistical methods and process and computational methods to automate them ensure quality of statistical methods and reproducibility of research.

We have developed low temperature selective Si and Si-based alloy (SiGe and Si:C) epitaxy processes for advanced transistor fabrications. By lowering epitaxy process temperature (≤ 700 °C), we have demonstrated elevated source/drain formation on ultra-thin (< 50 Å) body SOI transistors without Si agglomeration, smooth morphology of selective SiGe epitaxy with high [Ge] (>30 %) and [B] (>2E20 cm-3) concentrations, and selective Si:C epitaxy with high substitutional C concentration (>1 %). Also, we have increased growth rate of low temperature selective epitaxy processes by optimizing process parameters by adapting non-conventional deposition method.

Effective inhibitors of matrix metalloproteinases (MMPs), a family of connective tissue-degrading enzymes, could be useful for the treatment of diseases such as cancer, multiple sclerosis, and arthritis. Many of the known MMP inhibitors are derived from peptide substrates, with high potency in vitro but little selectivity among MMPs and poor bioavailability. We have discovered nonpeptidic MMP inhibitors with improved properties, and report here the crystal structures of human stromelysin-1 catalytic domain (SCD) complexed with four of these inhibitors. The structures were determined and refined at resolutions ranging from 1.64 to 2.0 Å. Each inhibitor binds in the active site of SCD such that a bulky diphenyl piperidine moiety penetrates a deep, predominantly hydrophobic S′1 pocket. The active site structure of the SCD is similar in all four inhibitor complexes, but differs substantially from the peptide hydroxamate complex, which has a smaller side chain bound in the S′1 pocket. The largest differences occur in the loop forming the “top” of this pocket. The occupation of these nonpeptidic inhibitors in the S′1 pocket provides a structural basis to explain their selectivity among MMPs. An analysis of the unique binding mode predicts structural modifications to design improved MMP inhibitors.

This study concerns the dynamics and management of the hairtail fishery (Trichiurus haumela) in the East China Sea. Virtual population analysis was used to assess the historical pattern of stock size and an age-structured production model was developed to simulate the historical and future changes of catch and stock of hairtail under different fishing strategies. The results show that the stock of hairtail has been declining in general since the beginning of the 1960s. In 1981, it was 275.103 metric tons, overfished but not very seriously. Subsequent management measures brought some positive effects to stock and catches and slowed down the decline, but they cannot change the status of overfishing of the stock. The current fishing regime will inevitably lead to more severe depletion of the stock and also decrease the catch in the end. To prevent further deterioration of the stock and maintain catches, any further expansion of fishing effort must be stopped. Alternatively, a longer closed season should be introduced or the age at first capture should be raised.

Spatial localization of bending waves was observed on a steel plate (72"X72"X1") decorated with lucite blocks (3.5"X3.5"X3") arranged in either a periodic or a random array. The exponential decay length of the localized modes is as short as 12 cm at 2.8 kHz, and increases with frequency as (f0 - f)-1, where f0 = 3.5 kHz is a quasi-mobility edge. The experimental data and finiteelement calculations suggest that the observed localization ofbending waves is due to the strong resonant scattering of bending waves by the shear modes of lucite/steel system. The generic nature of this localization phenomenon suggests its potential use as a attenuation mechanism for bending waves.